Emil “Tom” Frei III, an oncologist who developed the first complete cures for cancers with combination chemotherapy, died April 30 at his home in Oak Park, Ill. He was 89.

Frei was the emeritus director and emeritus physician-in-chief of Dana-Farber Cancer Institute. He previously held senior leadership positions at NCI and MD Anderson Cancer Center.

Frei’s breakthrough work began in 1955, with his arrival at NCI—he was recruited by the institute’s director, Gordon Zubrod, to do research in childhood leukemia. Within a year, he was named chief of the NCI’s Leukemia Section and later, chief of medicine.

Dissatisfied with the short-term acute lymphoma leukemia remissions produced by single-drug therapies, Frei and his colleagues began testing combinations of two or more agents to attack multiple aspects of leukemia cell growth.

“It was known that these drugs were cell-killers: some of them were derived from mustard gas,” NCI Director Harold Varmus said May 3 to the New York Times. “They were developed initially as toxic agents, not different from drugs that were used in warfare.”

With his colleague Emil Freireich, now at MD Anderson, Frei demonstrated that treatment with multiple chemotherapy agents could produce lasting remissions in children with acute lymphocytic leukemia.

At the time, this disease had been uniformly fatal, and single chemotherapy drugs could only bring it into temporary remission.

By combining as many as four drugs in a five-year treatment plan, Frei and his colleagues had increased the survival rate for pediatric leukemia to about 40 percent by 1965.

“If you give 60 percent of each dose, it’s the same as giving 100 percent of one or the other,” said Freireich to the New York Times. “But the effect on the tumor is additive.”

Today, the long-term survival rate for childhood leukemia is more than 80 percent, and combination chemotherapy is the foundation for treating many adult and pediatric cancers.

The Frei-Freireich collaboration also resolved chemotherapy-induced bleeding with infusions of blood platelets—allowing chemotherapy to be administered safely in larger, more effective doses.

“Dr. Frei and his colleagues saved the lives of literally millions of cancer patients by championing the then novel idea of combination chemotherapy for cancer over 40 years ago, and then developing effective combination regimens for previously incurable cancers,” Dana-Farber President Edward Benz said in a statement.

Frei moved to MD Anderson in 1965, where he served as associate scientific director of clinical research and as chair of the Department of Experimental Therapeutics.

In 1972, he joined Dana-Farber as physician-inchief, succeeding the institute’s founder, Sidney Farber. A year later, he became director of Dana-Farber and professor of medicine at Harvard Medical School.

With Dana-Farber colleagues Arthur Skarin and George Canellos, Frei developed a therapy for adults with non-Hodgkin lymphoma—one of the first chemotherapy regimens to produce a significant cure rate for the disease.

He joined fellow Dana-Farber researchers in pioneering the use of chemotherapy, surgery, and radiation therapy as a primary treatment for osteogenic sarcoma, a bone cancer of young adults. In the mid-1970s, he and his associates developed and tested drug combinations that boosted survival rates for breast cancer patients. He also worked with Dana-Farber investigators to pioneer the use of bone marrow transplants for various types of cancers.

“In addition to his pioneering work, Dr. Frei led the Dana-Farber Cancer Institute in its earliest days, nurturing the Institute through a remarkable period of excellence and growth,” Benz said. “His leadership was essential in establishing Dana-Farber as one of the world’s most outstanding centers for cancer research, prevention, and treatment.”

For a generation of workers in the Longwood Medical Area, Frei was a familiar sight, pedaling his bike to and from Dana-Farber.

Frei was born in St. Louis on Feb. 21, 1924, and grew up surrounded by artists and musicians.

His paternal grandfather founded the Emil Frei Art Glass Company in St. Louis, specializing in the design and manufacture of stained-glass windows. This company provided the glass panel in Dana-Farber’s Yawkey Center for Cancer Care, which features illustrations of chemical compounds and words like hope, courage, and inspiration.

Frei’s interests took a turn for science when, in his early teens, he read a book called Rats, Lice, and History by Hans Zinsser. The book planted the seeds of a lifelong passion for scientific discovery and a career-long search for a cure for cancer.

Drafted for active military duty in 1943 for World War II, Frei served under the V-12 Program until 1945. The U.S. Navy sent him to Colgate University for premedical studies.

He was admitted to Yale University Medical School in 1944 and received his MD in 1948. He performed his internship at St. Louis University Hospital and was a commissioned officer in the Navy Medical Corps from 1950-52, serving in Korea.

Over the course of his career, Frei published more than 500 papers in scientific and professional journals and was the recipient of numerous awards and honors. In 1972, he was awarded the Albert Lasker Medical Research Award in recognition of his scientific contributions.

He most recently lived in Chicago.

Frei was married to Elizabeth (Smith) Frei from 1948 until her death in 1986. He later was married to Adoria (Brock) Frei from 1987 until her death in 2009.

Frei is survived by his five children, Mary, Emil (and his wife, Lauren), Alice, Nancy, and Judy (and her husband, Larry Howe), and by 10 grandchildren.

“Tom Frei was one of a handful of physicians who developed combination chemotherapy for cancer and produced the first cures of childhood leukemia,” said David Nathan, president of Dana-Farber from 1995 to 2000.

“His was a massive contribution to medicine. Patients and trainees will remember him with deep