James F. Holland, a founding father of chemotherapy who helped pioneer a lifesaving drug treatment for pediatric leukemia patients, died on Thursday at his home in Scarsdale, N.Y. He was 92.

The cause was respiratory failure, his son Steven said.

Dr. Holland and his medical collaborators in the 1950s were scorned by some colleagues as research “cowboys,” as he put it, because they audaciously tackled what was considered an incurable disease and tried to treat it with several chemicals simultaneously, instead of sequentially.

When their research began, fewer than one in three children who were found to have acute lymphoblastic leukemia lived as long as a year. Today, as many as nine in 10 survive the disease, in which the bone marrow makes too many immature white blood cells.

Another clinical trial that Dr. Holland directed in the 1970s, to contain acute myeloid leukemia, a somewhat similar malfunction in blood cell production, resulted in what became the standard treatment.

His work extended lives. One former patient who was 49 when he enrolled in a clinical trial at the Roswell Park Comprehensive Cancer Center in Buffalo in 1970 — Dr. Holland was doing his research there at the time — is poised to celebrate his 97th birthday in June.

Dr. Holland went on to become chief of oncology at Mount Sinai Hospital in Manhattan.

Just as Dr. Holland helped establish oncology as a medical discipline, his wife, Dr. Jimmie Holland, who died in December, inaugurated the field of psycho-oncology.

While she cared for the emotional distress of cancer patients, he was more concerned not only with their individual medical condition but also with experimenting to discover universal remedies.

“Patients have to be subsidiaries of the trial,” he told The New York Times in 1986. “I’m not interested in holding patients’ hands. I’m interested in curing cancer.”

He acknowledged that some patients become guinea pigs, and that they sometimes suffer discomfort in the effort to eradicate tumors, but he said that even those who die provide lessons for others who will survive.

“If you do no harm,” Dr. Holland said, “then you do no harm to the cancer, either.”

In 1972, he shared the prestigious Albert Lasker Clinical Medical Research Award as chairman of an international consortium of physicians and scientists whose experimentation helped increase the life expectancy of children with acute lymphocytic leukemia. The award citation lauded “his great clinical skill, and his outstanding ability in clinical investigation.”

Dr. Holland was the president of the American Association for Cancer Research in 1970 and president of the American Society of Clinical Oncology from 1976 to 1977.

Last year, “Holland-Frei Cancer Medicine,” a reference book he wrote with Dr. Emil Frei III, another oncologist who blazed new frontiers in combining cancer remedies, was issued in its ninth edition. It was originally published in 2006.

“Jim Holland is one of the founding fathers of cancer chemotherapy,” said Dr. Vincent T. DeVita Jr., a Yale professor and former director of the Yale Cancer Center. “His work confirmed the curative potential of combination chemotherapy.”

Dr. Holland acknowledged that while experimenting with drug treatment sometimes amounts to trial and error, the primary killer is typically the disease itself.

“The thing to remember,” he said, “is that the deadliest thing about cancer chemotherapy is not the chemotherapy.”

James Frederick Holland was born on May 16, 1925, in Morristown, N.J., to the former Mary Louise Layer and Albert Holland.

His father, a county judge, nudged him toward a legal career, but James became mesmerized by biology in high school. He graduated from Princeton in 1944 and earned his medical degree at the Columbia University College of Physicians and Surgeons.

In addition to his son Dr. Steven M. Holland, who is director of the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, Dr. Holland is survived by four other children from his marriage in 1956 to the former Jimmie Coker, Mary, Sally, Peter and David Holland; a daughter, Diane Louise Holland, from his first marriage, to Lucille Rahe, which ended in divorce; and nine grandchildren.

His older brother Albert Jr., who died in 1988, was medical director of the Food and Drug Administration.

Dr. James Holland served as an Army Medical Corps captain in Germany after World War II. When his military duty was extended, he was promised a residency at Presbyterian Hospital in Manhattan when a vacancy developed.

Because his father had heart disease, Dr. Holland originally gravitated toward a career in cardiology. But what he thought would be an interim job at Columbia University’s newly opened Francis Delafield Hospital, which originally specialized in oncology, proved to be a perfect fit — especially after he met a 4-year-old leukemia patient, an only child named Josephine.

“I had come to love this child, and she loved me,” he recalled in Dr. John Laszlo’s “The Cure of Childhood Leukemia: Into the Age of Miracles” (1995). “Her remission was extremely meaningful to me, but by the same token, it was tragic when she relapsed and died.”

“She was only a child,” he said. “A crying child.”

Dr. Holland later worked at the National Cancer Institute in Maryland. He was only 28 when he became chief of medicine at Roswell Park, where he continued his clinical trials with what is now the John R. Oishei Children’s Hospital in Buffalo.

He and Dr. William Newton of the Children’s Hospital in Columbus, Ohio, were the first to administer two drugs, methotrexate and mercaptopurine, together to treat childhood leukemia.

In 1973, he established a department of neoplastic diseases at the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, where he was a distinguished professor at his death.

He also inspired the parents of a 21-year-old patient who died to create the T. J. Martell Foundation for Leukemia and Cancer Research, which raised more than $10 million for his laboratory.

Dr. Holland’s research went beyond leukemia into breast cancer and other tumors.

“If I can get a few more years, I sincerely believe I can help find a cure for other cancers,” he was quoted as saying in “Cancer Crossings” by Tim Wendel (2018). “It’s always a race, you see.”

Corrected on March 28, 2018: An earlier version of this obituary misstated the title of a book by Tim Wendel that quoted Dr. Holland. It is “Cancer Crossings,” not “Cancer Crossing.” It also misstated when Dr. Holland served as an Army Medical Corps captain. It was in Germany after World War II, not during the Korean War.

PHILADELPHIA, April 9 - A note of progress in the fight against acute leukemia in children was reported here today to the American Association for Cancer Research. The progress is in the matter of tactics against a disease that at present is considered incurable and usually is rapidly fatal. The disease is a cancer of the blood-forming tissues. As it progresses a huge number of abnormal cells accumulate in the bone marrow, the blood and other organs. In general the greater number of leukemic cells the more serious is the patient's condition. Drugs that can lower the number of leukemic cells drastically and keep their number low can provide respite from the disease. Sometimes they can preserve the patient's life for two years or longer.

Ultimately, however, the few cells not destroyed multiply and re-multiply in spite of the drugs and the disease completes its fatal course. Research in animals has shown that a single remaining leukemic cell can lead to a full-fledged renewal of the disease. Some scientists believe that the aim must be the eridication of every leukemic cell. So far, this seems not to be possible in human beings.

Today's report told of progress toward the objective of reducing a patient's leukemic cells to the absolute minimum. The report was based on a collaborative research endeavor that included 18 major medical centers here and abroad. The report was given by Dr. James F. Holland, chief of the Department of Medicine at Roswell Park Memorial Institute in Buffalo. His co-authors were Dr. Juliet Hananian and Dr. Paul Sheehe.

In half the cases studied, the report said, intensive drug treatment gave the patients periods of six months or more in which the disease symptoms were absent.

The important point about the remissions of disease symptoms, Dr. Holland said, is that they have continued so long without any treatment beyond the initial drug dosage.

Many Cells Destroyed

The scientists see this as an indication that the initial treatment destroyed a large percentage of the leukemic cells. The freedom from symptoms was long-lasting because it took the few remaining cells so long to repopulate. When the symptoms returned the children were given further treatment.

The study involved 88 children with acute leukemia. They were first treated with two drugs often used against the disease. These are vincristine and prednisone. Those who responded favorably were then divided into three groups, with each getting somewhat different treatment.

The method that worked best involved intensive brief treatments with three widely known anticancer drugs used in succession and followed by a fourth, which is new. The three standard drugs are methotrexate, 6-mercaptopurine and cytoxan. The new one is called BCNU. Its chemical name is bis-1-3-choloroethyl-nitrosourea.

All these drugs can be dangerously toxic.

The results obtained by using these drugs in combination, Dr. Holland said, vindicate the idea of using several potent drugs in succession to decrease the number of leukemic cells by successive waves of powerful chemical attack.

Dr. Holland also noted that the complexities of the treatment and the inherent hazards of the drugs demand that only trained teams at major research centers undertake such a project. The collaborative study was sponsored by the clincial branch. Collaborative Research, of the National Cancer Institute. The meeting here is being held at the Bellevue-Stratford Hotel.

Acute lymphocytic leukemia, which kills more young children In this country than any other disease, is yielding in ever‐in creasing numbers to intensive, combination therapy with po tent drugs and radiation. 

Some doctors, in fact, are beginning to speak cautiously of “curing” some cases of this disease, which, when untreat ed, claims the lives of more than 99 per cent of its victims.

In a report yesterday in The Journal of the American Med ical Association, a leading leu kemia researcher said that half of those children with acute lymphocytic leukemia may sur vive at least five years, free of disease, after what he called “total therapy.”

The researcher, Dr. Donald Pinkel of St. Jude Children's Research Hospital in Memphis, reported that combination treatments given to 37 children had resulted in seven children surviving for six years com pletely free of any signs of leukemia.

Previous studies have indi cated that children who survive this long have better than a 50 per cent chance of living out their lives as if they had never had leukemia.

Acute lymphocytic leukemia is a cancer of the blood‐form ing organs that results in wild overproduction of a form of white blood cells called lympho cytes. The cancerous lympho cytes fail to mature properly and are unable to carry out the normal disease‐fighting job of mature lymphocytes.

The disease kills 2,000 Amer ican youngsters between the ages of 3 and 15 each year. Al though pneumonia and influ enza take more young lives than leukemia, most of the vic tims of these infectious diseases are infants.

Yesterday's report described treatment programs that had been administered between 1962 and 1965. Since 1965, Dr. Pinkel said, changes made in the programs seem to be pro ducing better results.

After the treatment schedule administered in 1967 and 1968, for instance, 20 of 35 children have been continuously free of disease for three years or more, the Memphis pediatrician re ported. This result is more than 250 per cent better than that obtained from any treat ment schedule prior to 1965.

Single Drug Used

Yet Dr. Pinkel noted in an interview by telephone yester day, only a small percentage estimates range from 20 to 30 per cent—of young victims of acute lymphocytic leukemia are currently receiving anything like “total therapy.” Most re ceive “conventional” treatment with single antileukemic drugs that have a minimum of un desirable side effects but that are unlikely to produce a long term remission of the disease.

At a news conference here several weeks ago, Dr. James F. Holland of Roswell Park Memorial Institute in Buffalo, who is a leader in combination chemotherapy for leukemia, re marked that most children with the disease “are treated with the least amount of perturba tion, which is precisely the wrong thing to do.”

Dr. Pinkel said, “Acute lymphocytic leukemia can no longer be considered an in curable disease. Attitudes must change. Everyone should hop on the bandwagon and aim for cure for every child, with the reservation that these cures may not be permanent.”

Dr. Pinkel added that his in stitution no longer accepts pa tients who have received prior treatment, because leukemia that recurs after single‐drug treatment is nearly always re sistant to further treatment.

The total therapy that Dr. Pinkel described involves a drug regimen with potentially nasty side effects on the liver, gastro intestinal tract and immune defenses. In some cases, in fact, children who were freed of leu kemia have died as a result of the unwanted effects of treat ment, he said.

Dr. Pinkel's treatment starts with the administration of two antileukemic drugs—prednisone and vincristine sulfate — that can produce a remission of the disease with a minimum of ad verse side effects.

After remission, when the child is healthier, eating better and feeling well, he receives high doses of other antileukem ic drugs that he could not have tolerated when sick with his disease.

Supportive Care

The third step in treatment involves irradiation of his skull and spinal column (or irradia tion of the skull alone plus spinal injections of another an tileukemia drug, methotresate), with the aim of preventing re currence of the leukemia in the central nervous system. Several of Dr. Pinkel's studies have shown that when leukemia re curs, it most often shows up first in the central nervous system.

The last step is prolonged treatment with several drugs for two or three years even though the patient seems per fectly healthy.

At the same time, the children receive extensive supportive care—blood transfusions, anti biotic treatment and the like— whenever their disease or the drugs they receive produce ef fects that warrant it.

Dr. Holland and cancer re searchers at several dozen other hospitals around the country are using variations of this ap proach. As Dr. Pinkel pointed out, “The treatment of acute leukemia is still evolving. We won't stop changing it until we're sure we're getting maxi mum survival with the least possible hazards.

Dr. C. Gordon Zubrod, ex pert in cancer chemotherapy and leukemia at the National Cancer Institute, said that as a result of the modern approach to treatment, “Accute lympho cytic leukemia has shifted from an inpatient to an outpatient disease, which is remarkable in itself. Leukemia beds are empty because the kids are out and well. A lot of institutions are starving for patients.”

Through the use of the latest methods, more than 50 per cent of the children with acute lymphocytic leukemia can probably be cured, but only 20 per cent of those with the disease are currently receiving the best that medicine has to offer leading researchers said here yesterday.

The reasons are complex, the therapy experts said explaining that the treatment. is very expensive and only about three dozen institutions have experience with the new approaches.

But the main reason cited here is the failure of practicing physicians to keep up with new developments in cancer treatment and to refer patients to centers, where they can be most effectively treated.

Dr. James F. Holland, chairMan of an international group of researchers who have developed the new methods, said that in the case of acute lymphocytic leukemia, “being a guinea pig” is very much an advantage.

“The guinea pigs — the children in our research program—do, much better than the others,” Dr. Holland told a news briefing at the Commodore Hotel.

Latest Developments

The briefing was held in conjunction with The opening session of the National Conferente on Cancer Chemotherapy, Which will present the latest developments in chemical treatment of cancer to 2,500 attending physicians.

Dr. Holland, who, is chief of Medicine at Roswell Park Memorial Institute in Buffalo added that if children were not referred to the research centers for treatment, it would be impossible to develop further improvements in therapy because the centers would have insufficient numbers of patients on which to do meaningful studies.

Speaking to the meeting, which was sponsored by the American Cancer Society and the National Cancer Institute, Dr. Holland observed.

“I believe that practicing physicians should avail themselves of the closest leukemia center, referring their patient immediately, in the untreated state, for participation in the program's [that] may hasten cure.”

The importance of referring patients in the untreated state” was emphasized by Dr. Vincent T. DeVita of the National Cancer Institute, who reported that optional treatment was yielding long‐term survival in 70 per cent of patients with advanced cases of Hodgkin's disease.

“You only get one crack at cancer, and you'd better get it right the first Dr., Devita, said.

He explained that patients treated with less than the optimal methods were far more likely to suffer recurrences of their disease, and once eukemia or Hodgkin's disease returned, the chances of curing it. with another round of treatment were greatly reduced,

The current success in treating acute lymphocytic leu which kills 2,000„ children between the ages 3 and 15 in this country each year, is the result, of 15 years of cooperative research by smite 30 institutions here and abroad.

The research has involved a series of studies of different treatments for this fatal disease with each. new study combining the most promising features of the ones that preceded it.

As a result, each?new study has produced more survivors than the ones before it,. with the very latest approach expeeted to keep 90 per cent of the children alive for at least 3½ yeara. said.

This treatment schedule involves intensive treatment with. combination of potent. antidancer drugs continued treatment with smaller drug doses for indefinite period, and direct injection of the drug, methotrexate, into the spinal column to prevent recurrence in the central nervous system

A Treatment Program

Dr. Joseph V. Simone of St. Jude's Children's Research Hospital in Memphis reported that he was getting similar results with a treatment program that included irradiation of the brain, also aimed at preventing a relapse of the disease in the central nervous system.

In treating Hodgkin's disease, 90 per cent of patients whose disease is caught in its earliest stages can in effect be cured by radiation. In the Iater stages, Dr, DeVita reported a combination, of radiation and treatment with several potent drugs can save 70 per dent of patents.

Yet, Dr. Gordon Zubrod, sci, entifie director for ehemotherapy at the National Cancer Institute, estimated that. at the moment only about 20 per cent of acute lepkemia patients and a similar percentage of Hodgkin's disease patients” are being treated at the centers utilizing these therapies.

In the New York area, those medical centers studying the new leukemia therapy include Albert Einstein Columbia‐Presbyterian and Cornell University.

In 1968, when my mother was dying of cancer, drug treatment was the poor relation in the family of cancer therapies. Patients like my mother, with advanced cancer that had not responded to the standard treatments—surgery and radiation therapy—were pumped full of toxic drugs in the hope that some would grant them respite, albeit temporary, from the ravages of their disease.

Most doctors talked disparagingly about the drug therapist's “poison of the week,” and friends and relatives of cancer patients could not help but question the purpose and humanity of treating dying people with drugs that made them sicker while extending their lives by a few weeks or months at most.

I remember well how my mother's doctor had put it—“We have some drugs we'd like to try. We know they won't cure her, but maybe one or another will show some effects against her cancer, and this will help us develop therapies that may cure other cancer patients in the future.”

That doctor, David A. Karnofsky of Memorial SloanKettering Cancer Center in New York, was a highly competent and compassionate physician and an imaginative research scientist. He was also a man with vision, and today the drug, or chemotherapy he helped to develop promises to make the first significant dent in cancer mortality statistics since the common cancers, they can lengthen the lives of many cancer victims. When combined with surgery and radiation therapy, chemotherapy promises to improve the dismal survival rates associated with the nation's leading cancer killers. It also promises to eliminate the need for surgery to treat some cancers, or at least to reduce the amount of tissue the surgeon must remove, a possible benefit of great importance to women afflicted with breast cancer.

Furthermore, it is already established that chemotherapy can cure a number of less common forms of cancer. Acute lymphocytic leukemia once claimed the lives of 99 percent of the children who contracted it, within a few years of its detection. Chemotherapy makes it possible to hold the disease in check for a minimum of five years in more than half the children it afflicts. The vast majority of these long‐term survivors can be considered cured. Half the advanced cases of Hodgkin's disease, a cancer of the lymphatic system that typically affects young adults, can now be cured with chemotherapy (up to 90 percent of early cases are cured with radiation therapy). Choriocarcinoma, a cancer involving the uterus of young women, is 90 percent curable with anticancer drugs; once it was considered 90 percent fatal within a year. And the drug treatments, unlike surgery, preserve the woman's ability to bear children. Chemotherapy has also led to long‐term survival free of recurrence for more than half the patients afflicted with histiocytic lymphoma, testicular carcinoma, embryonal rhabdomyosarcoma, Ewing's sarcoma, Wilms's tumor, Burkitt's lymphoma and retinoblastoma.

For still other cancers, long‐term survival data are not yet available, but early results suggest that they, too, will yield to the attacks of powerful anticancer drugs. For example, even with amputation of the cancerous limb, osteogenic sarcoma, the leading bone cancer in children, has classically claimed the lives of 80 percent of its young victims within two years of diagnosis. Now, when amputation is followed by chemotherapy, 60 to 80 percent are alive and free of cancer two years after their disease is discovered.

In some cases, the use of chemotherapy before surgery can eliminate the need to amputate a cancerous limb, Only three years ago, 17‐year‐old Joseph, a Boston high‐school senior, would have faced the certain loss of much of his left shoulder and his left arm, where bone cancer had developed. But Joseph received four weeks of chemotherapy treatments before his surgery, and his tumor shrank. Surgeons at the Sidney Farber Cancer Center then removed a six‐and‐a‐half‐inch portion of the arm bone and adjacent muscle and replaced the bone with a metal rod. To their surprise and delight, they found no sign of living cancer cells in the section of bone they removed. Joseph underwent more chemotherapy for 18 months after his operation, and today he has been free of cancer for two years. He has full use of his left hand and can lift a weight of 18 pounds with his left arm.

“Chemotherapy is one of the causes of optimism in cancer‐therapy research today,” says Dr. Stephen K. Carter, director of the Northern California Cancer Program at Stanford University in Palo Alto. “The scientists who have worked in the field have a right to be proud of their accomplishments.”

Surgery and radiation are “local” therapies early 50's. when antibiotics and improved operating techniques increased the survival rates of those who underwent cancer surgery.

Dr. Karnofsky never saw the full realization of his vision, for in 1969, at the age of 55, he succumbed to the disease he had devoted his career to conquering. But every year, physician researchers who deliver the David A. Karnofsky Memorial Lecture describe the rapid and continuing development of chemotherapy as a major front‐line weapon against cancer.

As chemotherapy has changed from a last‐ditch, palliative measure to a primary mode of treatment, it has generated serious controversy. Some doctors warn that widespread use of toxic substances is irresponsible when their long‐term effects are not yet known. Like other drugs, anticancer agents are not selective in their attack and may easily damage normal as well as cancer cells. Patients have been known to die from side effects of anticancer drugs, which in addition to causing nausea, vomiting and loss of hair, can suppress functions of the bone marrow, where the body normally manufactures blood cells and cells that fight infections. The drugs may also damage the heart or the kidneys, and some are themselves capable of causing cancer in lower animals. In any case, the critics add, the public claims some doctors make for the powers of chemotherapy are raising unwarranted hopes about its ability to cure cancer

Proponents of chemotherapy respond that while the drug treatments are not proven cures for the most that treat cancer only at its primary site.

They fail to cure it in twothirds of the patients to which they are administered because cancer has spread to distant parts of the body by the time the main tumor is diagnosed. This spread, or metastasis, is often invisible to the surgeon who removes the tumor and, in fact, is usually undetectable by any currently available diagnostic technique.

Thus, when the surgeon tells the patient and his family, “We got it all,” he may really mean, “We got all the cancer we could see.” Microscopic colonies of cancer may have escaped his scalpel, and for this reason, anywhere from 10 percent to 80 percent of patients from whom the surgeon thought he removed “all” the cancer will experience a recurrence of the disease. (The rate of recurrence depends on the type of cancer.) “What is needed, says Dr. Vincent DeVita, director of cancer treatment for the National Cancer Institute, “is a treatment that can reach beyond the surgeon's knife and the radiation therapist's rays to remote areas of the body, wherever a hidden metastasis may have established itself.”

Chemotherapy is just such a “systemic” tool. Anticancer drugs can travel through the bloodstream to nearly all parts of the body, destroying cancer cells encountered en route. The drugs may combine with the genetic material (DNA) in cells to prevent them from dividing, or they may interfere with the cells’ metabolic processes. They are most effective against small numbers of rapidly dividing cancer cells. As Dr. Joseph H. Burchenal of Memorial SloanKettering Cancer Center explains, “The maximum dose of a particular anticancer drug may kill 99.9 percent of the cancer, no matter what their number. If there are 100 cancer cells, then all would be destroyed. But if there are 1 billion to 10 billion cells (as are contained in the smallest clinically detectable metastasis) a 99.9 percent cell kill would leave behind between 1 million and 10 million cancer calls”

Thus, when metastases are large enough to be seen or felt, chemotherapy may produce shrinkage or apparent “disappearance” of the tumors, but, with rare exceptions, it is unlikely to destroy every living cancer cell. Therefore, instead of withholding chemotherapy until the patient develops an obvious recurrence of his cancer, some doctors now give drugs at the time of initial treatment, in conjunction with surgery or radiation, to patients they believe are harboring invisible metastases.

They also tend to use combinations of two or more drugs instead of single agents. Dr. James F. Holland of Mount Sinai Medical Center in New York City, who is chairman of several national chemotherapy studies involving thousands of patients, explains that “theoretically, if enough of a drug could he given, it would eventually kill all the cancer cells. Unfortunately, it might also kill so many normal cells that the patient himself would he destroyed. Also, because cancer cells divide rapidly and can mutate, or change genetically, they may become resistant to the drug being used, just as bacteria can develop resistance to an antibiotic.” In combined chemotherapy, all the drugs attack the particular cancer cells, but their adverse effects on normal cells are spread out among several body tissues. One drug may damage the lining of the gut, another the bone marrow and a third the heart, while all three damage the cancer.

Nonetheless, chemotherapy —and especially combination chemotherapy—is a tricky and dangerous business, and every chemotherapist has had patients die from the side effects of drugs, sometimes at a time when their cancers seemed completely under control. Dr. Holland emphasizes that chemotherapy is far too risky to be administered by general physicians without special training. “It is critically important,” he says, “that chemotherapy be given by experts experienced in the use of these drugs, or under the guidance of experts who know how to adjust dosages and check regularly to be sure the patient's normal life‐sustaining cells are not overly attacked by the toxic chemicals.” In some cases, special supportive measures may he necessary. such as transfusions of certain blood cells or temporary germ‐free isolation.

Much of the current excitement and controversy over chemotherapy has focused on breast cancer, the leading cancer killer of American women and the leading cause of death among women in their early 40's. Breast cancer is the first major solid tumor that appears—on the basis of highly incomplete studies—to be yielding to the relentless assault of anticancer drugs.

So far, these studies have shown that the relapse rate among women whose cancer has spread to the lymph nodes near the breast (so‐called positive nodes) is much reduced if drugs are given for a year or so beginning right after surgery. One continuing national study involves a drug called L‐PAM, a nitrogen mustard. One group of women were treated with L‐PAM following their mastectomies. while a control group received a placebo. After two years. cancer has recurred in twice as many of the women who received the placebo. The study also has revealed that postoperative L‐PAM mostly benefits women whose cancers occurred prior to menopause. In the premenopausal women who were treated with LPAM, the recurrence rate so far is 80 percent lower than that of the control group.

Betty Ford, who was found to have two positive nodes at the time of her mastectomy in September 1974, was placed on L‐PAM after surgery; two years later, after she had completed the drug therapy, a thorough checkup showed no sign that her cancer had returned.

In another continuing study in Milan. three drugs are being used to prevent recurrence of breast cancer after mastectomies. Three years after the study of 386 women began, cancer has recurred in 26 percent of those who took the three‐drug combination for a year after their mastectomies, while the recurrence rate was 45 percent among women who received no postoperative treatment. For premenopausal women who received drug therapy, the recurrence rate was 14 percent, compared with 47 percent for the untreated women. Though the patients have suffered side effects, none have been serious enough to require their hospitalization.

“There's no question that chemotherapy for breast cancer is here to stay,” says Dr. Bernard Fisher, surgeon at the University of Pittsburgh and coordinator of the national L‐PAM study and other breast‐cancer trials. “Now it's a matter of finding out what chemotherapy is best for which patients.” He adds that “using chemotherapy. I have every reason to believe that in the immediate future lesser surgery will be as effective as radical mastectomy in treating breast cancer.”

These early findings have prompted some cancer specialists to advocate postoperative chemotherapy for every breast‐cancer patient with positive nodes. But since it requires at least 10 years of follow‐up study to form conclusions about this disease, other doctors challenge the rush to chemotherapy for breast cancer, calling it premature and possibly dangerous.

Dr. Mary E. Costanza of Tufts‐New England Medical Center in Boston is one of those who recommend caution in using chemotherapy to prevent a recurrence of breast cancer. She points out that the drugs suppress the immune response. may themselves cause cancer and can interfere with the bloodforming organs. She also notes Chat a sizable proportion of women with positive nodes do not develop a recurrence; for them, surgery alone turns out to be curative, so why take a chance that chemotherapy will shorten their lives? We do not know what the ultimate outcome will be,” Dr. Costanza says. “We may end up hurting more than we help.”

Dr. Holland of Mount Sinai says that critics like Dr. Costanza “fail to understand the biology of breast cancer.” It is a disease, he argues, that commonly has spread beyond the breast area by the time it is detected, obviating the curative potential of local therapy. Once it recurs at some distant site, cure is highly unlikely, no matter what kind of treatment is used.

Without postoperative treatment, Dr. Holland observes. “of those women with one positive lymph node, 50 percent will die of their disease; with two positive nodes, 60 percent; three. 70 percent and four or more, 85 to 90 percent. This year alone, more than 40,000 women in the United States will he found at the time of mastectomy to have cancer in the axillary [armpit] lymph nodes. This is the one time that cure is conceivable. If you wait until cancer shows up in their bones, liver or brain, it's too late.”

Dr. Holland added fuel to the controversy last year by calling the Italian study “of monumental importance” and its interim results “nothing short of spectacular” in an editorial in the prestigious New England Journal of Medicine. Others have called his assessments “premature” and “overstated.” He insists that continuing research will justify his views.

Critics of chemotherapy charge that the public is being sold a bill of goods about the procedure. However effective it may be in reducing recurrence of cancer after surgery or radiation therapy, they say, it still cannot be considered a broad “cure” for cancer. The cancers that can now be cured by chemotherapy, they point out, are rare and account for only 6 percent of cancer deaths. What progress, these critics ask, has been made against big cancer killers like lung cancer, which still claims the lives of nine in 10 of its victims?

Dr. Frank J. Rauscher Jr., who recently left his post as director of the National Cancer Institute to become director of research for the American Cancer Society, insists that the publicity about chemotherapy is justified. He readily admits that “the most progress has been made in curing relatively uncommon cancers.” But he and others maintain that the principles of curative therapy developed for rarer cancers are being applied to the commoner, more resistant forms, with some promise of success. And he adds that the cancers that now may be cured by chemotherapy are those “that attack children and young adults and are responsible for more years of life lost than, say, cancer of the lung or prostate, which are more common, but occur in older people.”

A young woman named Karen can verify his point. She was 17 when doctors diagnosed her choriocarcinoma, the once rapidly fatal cancer of the uterus. “My friends all thought I was a goner when they heard I had cancer.” she recalls. She suffered all the common side effects and some that were not so common from her three months of chemotherapy: She lost all her hair; she got sores in her mouth that made it difficult for her to eat; her weight dropped from 165 to 82 pounds; she suffered seizures, and the nerves in her legs became so inflamed that she had to walk with braces. But her cancer disappeared. and eventually, so did the side effects. Today, at 21, Karen is active and healthy. “I feel like a million bucks,” she says, “like it never happend.” ■

''We're interested,'' says Dr. Holland, ''in information.'' Patients Remain Subsidiary to Experiments Dr. Holland's domain at Mount Sinai, between Fifth and Madison Avenues at 99th Street, consists of an array of laboratories, examination rooms, data resource banks, offices and hospital beds.

He currently oversees 50 clinical trials for a broad spectrum of cancers, including those of the ovaries, bladder, bowel, breast, intestine, lung, neck, pancreas and blood.

All told there are more than 1,300 patients involved in these experiments; some have been under Dr. Holland's care for years. Patients whom other doctors had long since declared without hope still keep in touch with Dr. Holland and write him of their progress. Calls for his counsel pour in from around the world.

Yet the simple truth is Dr. Holland says he cares less about any one patient than he does about the quality of his research and the opportunity ultimately to save the lives of millions.

''Patients have to be subsidiaries of the trial,'' says Dr. Holland who, at 60, has been in cancer research for 30 years. ''I'm not interested in holding patients' hands,'' he said. ''I'm interested in curing cancer.''

His philosophy, though controversial, is straightforward. He disputes the commandment of the Hippocratic oath: ''First do no harm.'' He says he believes patients have to be subjected to discomfort as a means to eradicate their disease. Indeed, he says, some patients have to die in order to provide lessons for the generations who follow.

''If you do no harm,'' says Dr. Holland. ''Then you do no harm to the cancer either. I'm interested in the curability of these diseases.'' Pressure From Those Who Want to Participate It is Monday morning and Dr. Holland's private office at the hospital is crowded with patients, some of whom are involved in clinical trials, some of whom are not. Most are there for their weekly treatment of chemotherapy, which is often a combination of drugs, and do not require hospitalization. There are so many patients on this particular day there is not enough room for all of them to sit in the waiting room. The five office telephone lines all are busy.

There is one doctor on the telephone with a woman who might be a good candidate for a trial Dr. Holland is conducting for ovarian cancer. There is another doctor on the line who would like to refer a patient with breast cancer for a second opinion. This is the way most patients are referred - through doctors, who are familiar with Dr. Holland's work. Often they will mention a patient's profession and mental capacity or the fact that they have young children as a way of piquing Dr. Holland's interest.

A third line rings and it is a wealthy contributor to the hospital who demands to talk to Dr. Holland about a friend he would like to see receive Interleukin-2, a powerful new substance used to treat the white blood cells of some cancer patients. In recent weeks, the hospital has been inundated with such calls.

''Nobody needs it,'' Dr. Holland says firmly, obviously annoyed with the call. ''It's an investigational thing. We're picking people to put on it who fit the bill. It's got a lot of publicity, but no one's got any business telling people it's the only thing. I'll get my nurse and we'll see your friend and we'll decide whether she fits.''

Although well-connected individuals may get in to see Dr. Holland, he says he is adamant that only the best candidates who fit his research criteria are accepted. As it turned out, however, this particular patient was a 41-year-old woman with kidney cancer. Because of her age and the nature of her disease, she has been deemed an ideal candidate.

Dr. Holland says he is not interested in what patients want or their friends want but rather what best fits his research. For most experiments, patients who have received other therapies such as radiation or drugs, for example, are immediately eliminated as being ''contaminated'' for the purposes of his research. So are patients whose disease is so far progressed that they are not given a good chance of tolerating new medications. Still other patients are eliminated because they are assessed to be psychologically unstable and likely to back out in midstream.

Not long ago Dr. P. Alberto Paciucci, who oversees the Interleukin-2 program at the hospital - which involves extracting white blood cells from the body, treating them with the substance and then infusing them back into the bloodstream - eliminated a 50-year-old financier with leukemia because he had been exhibiting bouts of rage.

''He's emotionally unstable,'' Dr. Paciucci said. ''He's scared. He's apprehensive. He's a man who's had his way in life. He's now behaving like a 3-year-old with tantrums. He might change his mind. I don't want to jeopardize this study, invest a lot of resources for someone who might withdraw after one week.''

Dr. Holland put his philosophy about the selection process of patients this way: ''We're interested in people who will give us the cleanest answers,'' he said. ''The healthiest, the youngest, the strongest with a fatal consequence. Someone from whom we can get an unambigious response. The quicker we get a responsive system, the quicker we can have a way to use it.' 'For God's Sake, Take the Best'

Dr. Holland was in an examination room the other day with a 39-year-old buyer at Bloomingdales, who had been diagnosed several days before as having breast cancer.

The woman had been referred to Dr. Holland by a breast surgeon and had not as yet been treated. She told him that she first learned of the disease when she discovered a lump ''the size of a lima bean'' in her left breast during a routine self-examination. She said she had been conducting these examinations every three months or so for the past two years ever since her 59-year-old mother underwent breast surgery for cancer.

''Are you all wrung out or are you going to fight?'' Dr. Holland asked the woman, who sat across from him. Her husband was with her and the couple had just told Dr. Holland that they had two young children.

''I'm going to fight,'' the woman replied firmly.

''If you need chemotherapy we've got a pistol of a program,'' Dr. Holland continued. ''I don't believe the cures are good enough with surgery alone. I don't believe the cures are good enough with gentle chemotherapy alone. We are developing programs using more chemotherapy in a shorter period time. For God's sake take the best and I believe we've got the best.''

At this point, Dr. Holland sounded more like a salesman than a physician.

''Could it kill you?'' the woman asked. ''It could. But it won't.'' ''Will it make you sick?''

''It might,'' Dr. Holland said. ''You can go to lots of other places that will do it more gently and where you can go back to work. But I don't recommend it because the tumor comes back.''

''How come my mother didn't have to have any of this?'' the woman asked fighting back tears. She said she thought she would have surgery and that would be the end of it.

''Your mother was post-menopausal,'' replied Dr. Holland. ''I'm not satisfied with the results of today. Today too many women are dying to accept it as standard. My role is to find something better.''

''You don't know it's working if it's only been around four years,'' the woman challenged.

''You're right,''the doctor said. ''I can't prove it to you. But I'm convinced this is the proper approach. If I were 39 I wouldn't want to take a risk. The quality of your life is important to you. But so is a long life.''

The woman, who was scheduled to undergo surgery the following week to have the lump removed and determine whether the cancer had spread to her lymph nodes, said she would have to think about whether she wanted to be part of Dr. Holland's experiment.

After learning that the cancer had not spread, the woman decided not to participate.

Drugs Found Effective In Tests on Animals The anticancer drugs being tested at Mount Sinai have all been found effective against cancer in rats, mice and other laboratory animals. Some have never been tried before in man and are being tested to see how poisonous they are. These so-called Phase I trials test how much patients can withstand before developing serious side effects such as vomiting, bleeding, infection, blisters, blindness, hair loss, high blood pressure, death.

Other tests. known as Phase II and III trials, have less uncertainty to them about toxicity and examine a drug's therapeutic potential.

All drugs administered by Dr. Holland and his staff are approved for clinical trials by the Food and Drug Administration, which means they are not available for general use. The agency is kept apprised of all patient deaths as well as the progress in general of the research.

Lisa DeDominicis, a registered nurse, is employed full-time by Dr. Holland as a data management coordinator to oversee the vast quantities of paper work that such research and reporting entail.

Patients who agree to participate in an experiment at Mount Sinai must sign a consent form that informs them of the possible side effects. For a Phase I study of one drug, Taxol, for example, patients at Mount Sinai are told that not all potential side effects are known but that in large doses animals had developed bleeding, infection and vomiting.

For a Phase II study comparing combinations of another drug with two others, patients are told that they will be randomly assigned to one of two groups and could potentially develop kidney damage, facial swelling, and low blood pressure.

''If one treatment is found to be less effective than the other,'' the consent form reads. ''Patients will be informed and further treatment will be discussed. Depending on their response to the treatment, they may receive further drug therapy or supportive care alone later.'' Supportive care is a euphemism for palliative measures to assist the dying.

When doctors commence a Phase I study, they generally have evidence to believe a particular drug will be of benefit. But how much is needed to be effective and how much could kill a patient is often unclear. Last year of 63 patients involved in Phase I trials, 3 died directly as a result of drugs that were being taken, according to Dr. Holland's office. However, other deaths stemming from drugs arise as well.

The other day, for example, a 29-year-old woman with Hodgkins disease died at the hospital. She had been doing well and had been responding to the treatment.

''She died and I don't know why,'' said Dr. Roy B. Jones, 40, who works with Dr. Holland. ''The tumor shrinks but it's just too much. It's too potent.'' He said he believed the regimen of medication needed to be changed.

Dr. Holland does not try to hide the fact that these kinds of situations develop. He explains that this lack of clarity is the very reason why these experiments are so important.

He mentioned a 30-year-old man with testicular cancer, who not long ago was being treated with a certain experimental drug. The man was in his final hours, Dr. Holland said he thought, and he advised his staff to cut back the man's treatments to 20 grams per day. A young associate in his office disagreed and felt strongly that the dose be increased to 100 grams for the patient. Dr. Holland went along with the young doctor's advice. Today the patient lives.

''I can't tell ahead of time,'' said Dr. Holland. ''But neither can anyone else. The thing to remember is that the deadliest thing about cancer chemotherapy is not the chemotherapy.'' The point, he suggested, is that the deadliest thing is the cancer.

There is a chart in Dr. Holland's office that he frequently refers to. It reflects the results of an experiment he did starting in 1966 of children with leukemia and how at its start every one of the patients died but now more than half live.

''It's the guinea pigs who are first cured,'' says Dr. Holland, pointing to the chart. Debate on Selection Of Test Subjects It is 8 A.M. Tuesday morning and Dr. Holland is in a meeting with two statisticians and two other doctors to discuss a new experimental treatment at the hospital.

Specifically they are interested in seeing whether applying a drug directly to the abdominal cavity is more effective than giving it intravenously in patients with cancer of the ovaries. They plan to assign patients at random to one of two groups to determine which procedure is more beneficial.

At the meeting, Dr. Carmel J. Cohen, a gynecologist, questioned whether older patients could tolerate abdominal injections of the drug. Dr. Holland replied that an 80-year-old woman had done fine. The group proceeded to review statistics and examined some graphs.

Then Dr. Cohen wondered out loud about the dilemma that many doctors face in partaking in experiments that involve control groups. He asked whether doctors would be able to continue to assign patients at random if one therapy seemed to emerge as more effective.

''That won't be a problem,'' Dr. Holland said quickly, dismissing the question. ''We won't know the answer for five years.''

In an interview afterward, Dr. Cohen said he had not always believed in clinical trials; that for years he did not want to subject his patients to medicine's uncertainties. But over the years, he said, he has changed his mind. About 10 years ago, he said, a treatment came along and he permitted a number of his patients to be included in it. It emerged to be far more effective than what was routinely being prescribed.

''Had I continued,'' said Dr. Cohen. ''I would have been consigning most of my patients to death. I have no dilemmas anymore about clinical trials. With a trial you get at least as good care and may get even better care.'' Developing Attachments To Patients The rooms along 6 North at Mount Sinai are where patients involved in clinical experiments are treated if they must be hospitalized. They look like hospital rooms elsewhere. Visitors come and go. Time is measured by rounds of blood tests, doctors' visits, the arrival of the dinner trays.

It was a good day the other day on 6 North. Two patients - a 65-year old South American businessman and a 37-year-old woman from New Jersey - each of whom had been receiving treatments of Interleukin-2 - were going home after being in the hospital for nine weeks. The effects of the treatment are still unclear.

''I feel wonderful,'' said the South American, who had been diagnosed to have an inoperable kidney tumor.

''I just want to see my children,'' said the woman, who has three young children. Since the treatment apparently has not worked and she is planning to return to the hospital for a bone marrow transplant.

Mary Schlegel, a physician's assistant, was on hand that day as these two patients were leaving. Each stopped to give her a hug. Miss Schlegel watches patients come and go all the time on 6 North. To her, they are not numbers and ''events'' but individuals with anxious loved ones.

''You get very attached to the patients here,'' said Miss Schlegel, who is 31. ''I'd like to think that what we're doing is going to make a difference. That it will make them live. But in the back of my mind I think it may kill them too. Some of these things are so toxic you wonder if they wouldn't be better off dead. Am I ruining what they have left? Maybe they should be home. Spend time with their children. People don't know how sick they get on these drugs. But I am constantly overwhelmed by how much people want to live.''

Dr. Jones, who works with Dr. Holland, says he is troubled at times too by the suffering but believes in what he is doing.

''If we cause short-term harm it is for long-term benefit,'' said Dr. Jones. ''It may not benefit them. But other people and they themselves might benefit. I do harm to patients everyday. I make them vomit. I give them infections. But what you do is reasonable if there is benefit to justify the suffering. You may never be sure what you're doing is right. But the solace is in the fair bargain.'' Treatment Itself Can Cause Problems Dr. Paciucci, who oversees the Interleukin-2 program, was in with a 48-year-old woman the other day, who three years ago was suffering from ovarian cancer. She was placed on experimental therapy at Mount Sinai and appeared to be cured. But recently she learned that this therapy had given her the beginnings of leukemia, one of the side effects of the experimental drug.

''I'm not telling you this is like an ulcer,'' Dr. Paciucci said, explaining the woman's condition. Then he told her of another experimental treatment for which she would be eligible.

''This is a new thing,'' he said. ''In New York we are the only ones trying to know whether this is the best treatment. We will know only after 100 patients with your disease have been treated. It is not a run of the mill treatment. It must be done under medical supervision. It is a drug that is not available for sale.'' ''Is it toxic?'' the patient asked. ''It is not toxic but might induce minor nausea.''

''My prognosis is greatly changed,'' the woman said sounding discouraged.

''Your prognosis I believe is excellent.'' Dr. Paciucci said. ''Someone like you is now normal,'' he said, explaining that she had not yet developed a full-blown case of leukemia. The drug he was proposing is believed to be capable of preventing the disease's spread. ''I don't know how many will respond. You would be the fourth or fifth patient.''

''Guinea pig is the word,'' the woman said with a laugh. The doctor did not say anything. ''But if they did well then I'll do well,'' the woman added cheerfully. ''I consider myself lucky. Do you want to tell me the long term effects of this or don't you know.''

''We don't know,'' Dr. Paciucci said.

Because of her will to live, doctors considered her an ideal patient.

''I haven't finished living yet,'' the woman said with determination. ''I'm so lucky they have this drug for me.'' She agreed to participate. Each Patient Is 'A Piece of Data'

The way Dr. Holland looks at it 500,000 people will contract cancer this year. If every one of them were willing to be subjected to research, medicine would come up with a cure sooner.

''Every patient becomes a piece of scientific data,'' Dr. Holland says.

In addition to seeing patients, training physicians, keeping informed of developments around the world, Dr. Holland is actively involved in raising money for research at Mount Sinai. He says he fears that with new limits on what insurance companies will pay for specific illnesses, he will have to eliminate patients who cannot afford treatments.

It angers him that Medicare will not pay the medical costs of patients, who are the subjects of research. Over the years, Dr. Holland has sought private funds and helped establish the T. J. Martell Foundation for Leukemia and Cancer Research, which has contributed over $10 million to his laboratory.

Dr. Holland, who is married to Dr. Jimmie Holland, the Chief of Psychiatry at Memorial, has suffered several heart attacks and underwent coronary bypass surgery in 1980.

He and his wife have five children and he has a daughter from a previous marriage. Nevertheless, Dr. Holland is in his office every day at 7:45 A.M. and never leaves before 8 P.M; often standing over his charts and graphs like a commander in chief preparing for battle.

Why, he was asked, is it so important for him to cure cancer?

''It's the most imporant thing I can grasp and do something about,'' he said. ''I've been in the field at the critical time. I find the expanse of it challenging. Once you're in it, the only thing is to seek prevention and cure. Not to hold people's hands and help them die gracefully. I have a fundamental love of life for others.''

After her surgery, my Mother would ask how her growth was and I'd say, 'Your growth is fine,' " says Dr. William G. Cahan, senior attending surgeon at Memorial Sloan-Kettering Cancer Center in New York. "She died at 91 without ever hearing the word cancer . It was a death-knell word then. It would have burdened her. So I went along, which turned out to be a nice bit of palliation. Today, we can't keep truth from people, nor do I say we should. But total candor can be the rape of hope."

Truth never used to be an issue in medicine. If the news was bad, it was simply not told, a reflex response first identified by Dr. Ronald M. Weintraub, chief of cardiothoracic surgery at Beth Israel Hospital in Boston, as the Uncle Moe Shouldn't Know Syndrome: The family begs the doctor to lie to the patient, which the doctor does, and would have done anyway.

The doctor has lied ever since Hippocrates, and in most of the world, truth-telling is still considered bad medicine. Dr. Jimmie Holland, chief of psychiatry at Sloan-Kettering, recently surveyed oncologists in 22 countries. She says: "In much of Europe, South America, most of Asia -- they consider it unethical to tell. They say, 'America is so brutal, you make it so difficult for the patient, and we are kind and gentle.' "

But just yesterday, America was identically kind and gentle. We are, after all, truth parvenus. In 1961, in a study published by The Journal of the American Medical Association, 9 out of 10 doctors said they generally concealed a cancer diagnosis from their patients. But by 1977, the ratio had been reversed: More than 9 out of 10 said they usually told the truth.

In the decade between, the threat of malpractice suits and powerful antiauthoritarian forces -- the consumer advocacy movement, the anti-Vietnam War movement, the women's and civil rights movements -- had pushed doctors toward the doctrine of informed consent. And with advances in oncology and heart surgery, bad news was not always so bad anymore. It hurt less to hear and less to tell.

But nobody had ever been taught how to tell, and many doctors and medical ethicists recall it as a time of wretched excesses. "You're dying, you know, and we really have to talk about it," George J. Annas, a lawyer and ethicist who is professor of health law at the Boston University School of Medicine and Public Health, remembers zealous doctors saying. "We called it terminal candor."

Carol Schert of Greensboro, Md., whose son Mark died of cystic fibrosis in 1980, still weeps to recall how she learned the diagnosis: "He had been in the hospital for nine weeks, and we still didn't know what was wrong, and then one day the doctor told me: 'It turns out he has cystic fibrosis. Do you know what that is?' I said, 'No.' He said, 'Well, that's what he has,' and walked out of the room."

There was a lot of what the psychiatrist Dr. Willard Gaylin labels "truth-dumping" -- disclosing every possible treatment and side effect, down to the remotest chance that a certain pill may produce a pimple on the nose, and then leaving the patient to decide what to do. "In the release of information, caring is the great modifier," he says. "This was informing without caring."

Today, unvarnished truth seems to have yielded to what one doctor calls a slightly varnished truth, by which he means not a lie but a good spin on bad news. As in: A patient comes to Dr. Weintraub at Beth Israel as a candidate for open-heart surgery. He is too high-risk and is turned down. Dr. Weintraub says: "The absolute truth would have been to say, 'You are so sick and your heart is so bad that if I operate on you I'll kill you.' Instead, I said: 'I've looked at the alternatives. Surgery would carry high risk and I think that, in your situation, continued medical therapy is the way to go.' It's euphemism, sure. He was sent to me because medicines weren't working well anymore. But you don't need to hit people over the head."

Dr. James F. Holland, an oncologist and chairman of the department of neoplastic diseases at Mount Sinai Medical Center in New York, agrees: "Say a patient asks, 'Do I have a chance?' It serves no useful purpose to say, 'Yes, about one in a hundred,' though that may be statistically so. But it is useful to say, 'Yes, but you must work for it, because the treatment won't be easy.' Then they can concentrate on the positive elements of treatment. People need the possibility of hope."

It might be called the "bad news, but" school of truth-telling: "The treatment hasn't worked, but we never know what's just around the corner."

Dr. Cahan, whose autobiography, "No Stranger to Tears," looks back on 50 years of surgical practice, recalls how antibiotics suddenly appeared around that cosmic corner, "and people who had been dying like flies, of ruptured appendixes, blood poisoning, pneumonia, suddenly were living as if by a miracle."

Even in dealing with AIDS, perhaps especially with AIDS, they hold out that straw of optimism.

" 'This is the end, I've had it.' That's how cancer patients talked 30 years ago, and it's exactly how AIDS patients talk today," says Dr. James J. Strain, professor of psychiatry at Mount Sinai. "We tell them that, though the breakthrough hasn't yet come with AIDS, it will, and, meanwhile, whatever happens, we will be right here with you and we will keep you free of pain."

At the Mount Sinai School of Medicine, a doctor sits facing a patient who seems distraught beyond words.

"Can you show me just where the pain is?" the doctor asks.

The patient presses her stomach and sighs heavily.

He says: "You seem worried. Is something worrying you?"

"The pain," she whispers.

"Why does it worry you? What do you think it is?"

Her mouth opens and the word falls out: "Cancer."

The doctor grimaces and consults the ceiling. Suddenly he says, "Time out."

The "patient," a professional actress, freezes. The "doctor," a second-year medical student, faces his audience: his classmates and their professor, Dr. Mark H. Swartz.

"Why did you want time out?" Dr. Swartz asks him.

"I wasn't sure what to say next. She seems so sad, I wonder if it's psychological. Can I tell her it's probably not cancer?"

"Is that the truth?"

"I don't know. It could be a lot of other things."

"Then that's the truth: You don't know, and it could be a lot of other things. Just tell the truth," the professor says, and the show goes on.

This unfrivolous game, using actors trained to simulate illness, is played at the Morchand Center at Mount Sinai, where students explore such issues as ethics, empathy, coping with death and dying, and truth-telling.

Medical schools used to ignore all that. But as hospitals have grown more competitive and society more litigious, the profession has seen an urgent need to improve its bedside manners. Today, of 126 accredited medical schools in the country, 117 now require some study of physician-patient relationships, admissions committees are trying to measure applicants' "humanity" and the biggest buzz phrase is "communication skills."

For a practice now so broadly endorsed, truth-telling is little understood. There is plenty of passionate conviction but no conclusive evidence that disclosure is "better" (or worse), in any medical sense, than the beneficent lie.

"I saw a woman whose ovarian cancer had come back after three years," says Dr. Stuart E. Lind of Harvard Medical School, who has written extensively on disclosure. "The surgeon had never told her it would probably recur. Was it better for her to have those years free of worry? I think it's better to know the truth. But I can't be sure. And there may not be a simple answer ever."

Among medical ethicists and philosophers, the issue is not what is "better": "The point is the right to know ," says the ethicist George Annas. "You can withhold the truth only if the patient says, directly, 'I do not want to know.' "

But doctors insist that they must also listen to what the patient doesn't say. Dr. Arthur W. Ludwig, an internist at Mount Sinai, tells this cautionary tale: "When I was an intern, Fiorello La Guardia was admitted for exploratory surgery. He said to me: 'Ludwig, these sons of bitches will never tell me the truth. I want you to swear that you will.' I swore. He was loaded with cancer and died a few months later. But he never once asked me. And I never told him."

It's the same old paternalism, the purists say. It is a necessary beneficence, the compromisers say.

"Which is worse? It's a value judgment," says Dr. Jimmie Holland at Sloan-Kettering. "Paternalism had its downside, but so does patient autonomy. We need a middle ground. But these changes come from a society's demands, and society isn't sure what it wants, either."