WASHINGTON — When James F. Holland began his medical career in the early 1950s, oncology scarcely existed as a discipline. Cancer was considered more or less incurable. Those who experimented with chemotherapy were deemed part of the ‘‘lunatic fringe,’’ wasting their talents on experimental drug tests.
What’s more, critics said, some of these new clinical trials ended in death — violating one of medicine’s fundamental precepts, to ‘‘first do no harm.’’
Dr. Holland, a deep-voiced physician fond of colorful, whimsically patterned ties, demurred.
‘‘If you do no harm,’’ he told the New York Times in 1986, ‘‘then you do no harm to the cancer either. I’m interested in the curability of these diseases.’’
By the time of his death, on March 22 at 92, Dr. Holland had helped orchestrate a sea change in medicine’s approach to cancer, leading large-scale research studies that successfully demonstrated the effectiveness of chemotherapy.
Through a technique known as combination chemotherapy, in which multiple drugs are used in concert, he effectively cured one form of childhood leukemia and laid the groundwork for the treatment of countless other types of the disease, including lymphoma and colorectal, breast, and lung cancer.
He did so while treating thousands of patients at the Icahn School of Medicine at Mount Sinai in Manhattan, where he was a professor of neoplastic diseases, and while serving as the head of groups including the American Association for Cancer Research and the American Society of Clinical Oncology.
‘‘He was one of the great pioneers of the field in its early days,’’ said Vincent DeVita, an oncologist and epidemiologist who built on Dr. Holland’s work to develop a treatment for Hodgkin’s lymphoma. ‘‘People thought the concept of drugs curing cancer was beyond sanity. . . . The idea of using drugs in combination was even crazier.’’
Dr. Holland was not the first to treat cancer with multiple drugs at once.
After joining the National Cancer Institute in 1953, he was introduced to Lloyd Law, who had found that mice with leukemia responded better to drugs that were given in combination than to drugs given in sequence. In effect, the cancer was deluged by a molecular assault, unable to stave off attacking chemicals that targeted different pathways inside the cells.
Drawing on Law’s research, Dr. Holland began testing the use of combination chemotherapy on children with acute lymphoblastic leukemia (ALL), a cancer that affects white blood cells. He continued his research after moving to what was then the Roswell Park Memorial Institute in Buffalo, and with oncologists such as Emil ‘‘Tom’’ Frei and Emil Freireich showed the chemicals’ effectiveness on humans.
‘‘While Tom and Jay [Freireich] did the studies that showed you could cure childhood leukemia, it was Jim [Holland] who harnessed that information into large-scale clinical trials and proved it,’’ DeVita said in a phone interview. The studies were increasingly fine-tuned and complex, with eligibility requirements and randomization plans that made them a prototype for subsequent research trials.
‘‘We were looked on as cowboys,’’ Dr. Holland later said, ‘‘but we could point to remissions, which other people didn’t have, and some of them were long-lasting.’’
In 1972, Dr. Holland received the Albert Lasker Clinical Medical Research Award, which cited his ‘‘outstanding leadership’’ of Acute Leukemia Group B, an international research consortium that he and Frei helped establish. The group had studied 1,538 patients with ALL since 1956. At that time, the citation read, ‘‘only 30 percent of children lived one year from the onset of their disease. Now, 90 percent do.’’
The survival rate for the disease is now more than 80 percent, according to the American Association for Cancer Research.
Dr. Holland died at his home in Scarsdale, N.Y., of complications of cardiovascular disease, said his daughter Mary Holland.
He leaves a daughter from his first marriage, Diane Holland of Convent Station, N.J.; five children from his second marriage, Steven Holland of Bethesda, Md., Sally Holland of Scarsdale, Peter Holland of Annapolis, Md., and Mary Holland and David Holland, both of Manhattan; and nine grandchildren.
