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 T. DeVita Jr., 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, a cancer that affects white blood cells. He continued his research after moving to what was then Roswell Park Memorial Institute in Buffalo, and with oncologists such as Emil “Tom” Frei III and Emil J. 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 he and Frei helped establish. The group had studied 1,538 patients with acute lymphoblastic leukemia 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.
James Frederick Holland was born in Morristown, N.J., on May 16, 1925. His father was a judge who suffered from heart disease, leading a young Dr. Holland to initially pursue cardiology, and his mother was a homemaker who yearned to become a nurse.
Jim Holland graduated from Princeton University in 1944 and from Columbia University’s College of Physicians and Surgeons three years later. He served as a captain in the Army Medical Corps, and after returning to New York in 1951 was surprised to learn Columbia Presbyterian Hospital, where he planned to begin his career, was fully staffed.
Dr. Holland was told he could work instead at Francis Delafield Hospital, a newly opened cancer research center led by oncologist Alfred Gellhorn, and switch to Columbia once another resident dropped out “for tuberculosis or psychiatric reasons.”
An opening appeared just three months later, but “by then I had taken care of a child with acute leukemia and put her into remission,” Dr. Holland later recalled. He decided to stay and soon made leukemia the focus of his research.
Dr. Holland joined Mount Sinai in 1973 after spending a year in the Soviet Union as part of an oncology exchange program. (“You will see that our medicine will remind you of your Wild West,” one leading Soviet researcher was said to have told him.) He made the trip with his children and wife, Jimmie Holland, who was credited with founding the field of psycho-oncology. While Dr. Holland treated the bodies of cancer patients, she addressed their mental and emotional states. She died in 2017.
A previous marriage to Lucille Rahe ended in divorce.
Dr. Holland died at his home in Scarsdale, N.Y., of complications of cardiovascular disease, said his daughter Mary Holland.
Survivors include a daughter from his first marriage, Diane Holland of Convent Station, N.J.; five children from his second marriage, Steven M. Holland of Bethesda, Sally Holland of Scarsdale, Peter Holland of Annapolis, and Mary Holland and David Holland, both of Manhattan; and nine grandchildren.
His older brother Albert H. Holland Jr., who died in 1988, was medical director of the Food and Drug Administration.
In later years Dr. Holland joined Frei in co-editing the textbook “Holland-Frei Cancer Medicine,” now in its ninth edition, and helped found the African Organization for Research & Training in Cancer. He remained focused on research, however, and on working to save the lives of patients — individuals whom he remained close with over the years, through letters and phone calls that continued well after they left his hospital, but whom he also saw as “subsidiaries” of clinical trials that could help save thousands of lives in the future.
“I’ve been in the field at the critical time,” he told the Times. “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.”