Chemotherapy Pioneer James Holland, MD, Dies at 92

Megan Brooks

March 27, 2018

James F Holland, MD, a pioneer in cancer chemotherapy, died March 22 at the age of 92 at his home in Scarsdale, New York. The cause was complications of cardiovascular disease.

At the time of his passing, Holland was distinguished professor of neoplastic diseases in the Department of Medicine at the Icahn School of Medicine at Mount Sinai in New York City.

Dr James F Holland

"Dr Holland was a legendary oncologist and a celebrated member of the Mount Sinai community," reads a statement sent to staff at Mount Sinai and to Medscape Medical News. "An internationally renowned leader in the field of medical oncology, Dr Holland helped pioneer the use of combination chemotherapies for the treatment of childhood acute lymphoblastic leukemia. With this achievement, a disease though to be incurable was transformed into one with an 80 percent survival rate."

Holland was "one of the founding fathers of cancer chemotherapy," Vincent DeVita Jr, MD, from the Yale Cancer Center, New Haven, Connecticut, said in an ASCO Post article celebrating Holland's 90th birthday. 

Holland served as the American Society of Clinical Oncology (ASCO) president from 1976 to 1977. In 1982, he was awarded ASCO's highest scientific honor, the David A. Karnofsky Memorial Award and Lecture.

Holland was born in 1925, in Morristown, New Jersey. After graduating from Columbia University College of Physicians and Surgeons and completing his residency, Holland served as a captain in the US Army Medical Corps during the Korean War. 

An Icon in the Field

Holland began his pioneering work in oncology before it was established as a formal medical discipline. He was known for his involvement in developing groundbreaking cooperative clinical trial protocols for the treatment of leukemia.

In 1953, Holland joined the National Cancer Institute (NCI), where he led a clinical trial testing the combined use of two chemotherapy drugs (methotrexate and 6-mercaptopurine) on acute leukemia. The trial was still in progress the following year when Holland moved to the Roswell Park Cancer Institute (now Roswell Park Comprehensive Cancer Center) in Buffalo, New York. When the NCI's new chief of oncology at the time agreed to continue the trial, it became the first multicenter study of acute leukemia.

[Holland was] an absolute giant, and so incredibly influential. Dr Candice Johnson

"Dr Holland was such a force in oncology, and such a model for how to care for your patients with both passion and ingenuity," Candice Johnson, PhD, president and CEO of Roswell Park Comprehensive Cancer Center, wrote in email to Medscape Medical News.

"We're so inspired by all he accomplished, and proud to know that some of his most groundbreaking ideas first took root during his time at Roswell Park," said Johnson. "When I think of how central a concept combination therapy is to the field of cancer treatment today, I can't help being especially grateful for all Jim Holland and his colleagues have done for cancer patients across many decades. Our hearts go out to his family for the loss of this man we all loved and admired. He was an absolute giant, and so incredibly influential," Johnson added.

While at Roswell Park, Holland continued his collaboration with NCI and started collaborating with Children's Hospital of Buffalo, which led to formation of the Acute Leukemia Group B, a government-funded research collaboration that later became known as the Cancer and Leukemia Group B (CALGB).

Holland collaborated closely with another pioneer in combination cancer chemotherapy,  oncologist Emil "Tom" Frei III, MD, who passed away in 2013. From the 1950s to the 1980s, either Holland or Frei chaired the CALGB. The two teamed up to write the influential oncology reference book Holland-Frei Cancer Medicine, now in its ninth edition.

Holland and Frei, along with oncologist Emil Freireich, MD, from MD Anderson Cancer Center in Houston, Texas, also pioneered the 6-mercaptopurine, vincristine, methotrexate, and prednisone (POMP) regimen, demonstrating that it produced sustained remission in children with acute lymphoblastic leukemia (ALL).

The use of combination chemotherapy transformed ALL from an incurable disease to one with a survival rate of more than 80%.  In 1972, Holland was awarded the prestigious Albert Lasker Basic Medical Research Award for his contributions to the concept and application of combination chemotherapy in the treatment of acute leukemia in children.

Holland and his colleagues also developed the "7 + 3" regimen of 3 daily injections of daunorubicin and 7 days of intravenous cytarabine, a schedule now widely used to treat acute myelocytic leukemia.

Holland was a member of the American Association for Cancer Research (AACR) since 1955 and served as AACR president in 1970-1971.

Holland was "an icon in the field who positively impacted the lives of patients with many types of cancer, improving outcomes and providing them with new hope," AACR chief executive officer Margaret Foti, PhD, MD, in a statement.  "His rigorous approach to clinical research, deep commitment to collaboration, charismatic personality, and outstanding leadership skills brought him the enormous respect and admiration of his colleagues."

Holland was married to Jimmie C Holland, MD, known internationally as the founder of the subspecialty field of psycho-oncology, who died in 2017, as reported by Medscape Medical News. The Hollands are survived by their six children and many grandchildren.

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