Dana-Farber mourns the passing of Emil 'Tom' Frei III, MD, eternal optimist and father of combination chemotherapy

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Led Dana-Farber from 1973-1980

Emil "Tom" Frei III, MD, former physician-in-chief of Dana-Farber Cancer Institute, has died. His work helped bring about the first complete cures for pediatric leukemia patients and led to more effective treatments for adult malignancies ranging from breast cancer to bone cancer. Dr. Frei, 89, died on April 30.

With his colleague and near-namesake Emil Freireich, MD, of the University of Texas, M.D. Anderson Cancer Center, Dr. Frei became known as the "father of combination chemotherapy" for demonstrating in the 1950s and 1960s that treatment with multiple chemotherapy agents could produce lasting remissions in children with acute lymphoblastic leukemia (ALL).

At the time, this disease had been uniformly fatal, and single chemotherapy drugs could only bring it into temporary remission. Today, combination chemotherapy is the foundation for treating many adult and pediatric cancers.

"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," said Dana-Farber President Edward J. Benz, Jr., MD. "This approach has led to cures in many patients with cancer. The majority of patients with certain forms of childhood leukemia, Hodgkin disease, testicular cancer and some other cancers can now expect to live long and high-quality lives because of his contributions.

"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 continued. "His leadership was essential in establishing Dana-Farber as one of the world's most outstanding centers for cancer research, prevention, and treatment."

Known as an eternal optimist, Dr. Frei was admired by colleagues for his ability to inspire them to challenge their intellects and preconceptions. He was equally beloved by patients, many of whom returned to him for annual checkups long after their treatment had been completed. He was a favorite of young cancer patients in Dana-Farber's Jimmy Fund Clinic when he dressed up as Big Bird or Darth Vader for parties.

His breakthrough work began in 1955 with his arrival at the National Cancer Institute, where he was recruited by the Institute's director, Gordon Zubrod, MD, 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 ALL remissions produced by single-drug therapies, Drs. Frei, Freireich, James Holland, MD, and others began testing combinations of two or more agents to attack multiple aspects of leukemia cells' growth. The research was driven by Dr. Frei's ability to see promise where others saw discouragement.

When Dr. Frei and his colleagues began these combinations in patients, only a few were cured. Undeterred, he found lessons in these survivors that could improve therapies in the next round of trials. He demanded the same single-mindedness in those he worked with.

The Frei-Freireich team also tackled the problem of chemotherapy-induced bleeding and showed that infusions of blood platelets allowed chemotherapy to be given safely in larger, more effective doses.

Today, combination chemotherapy and platelet transfusions result in complete and permanent cures for three of every four children with ALL. The method is credited as a very significant advance in saving the lives of patients with cancer.

Dr. Frei moved to M.D. Anderson Cancer Center in Houston in 1965, where he served as Associate Scientific Director of Clinical Research and chaired the Division of Experimental Therapeutics. In 1972, he joined Dana-Farber as Physician-in-Chief. After the Institute's founder, Sidney Farber, MD, passed away early the next year, Dr. Frei became Director of Dana-Farber and Professor of Medicine at Harvard Medical School.

With Dana-Farber colleagues Arthur Skarin, MD, and George Canellos, MD, he 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 initiating 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.

Under Dr. Frei's stewardship, Dana-Farber became one of the world's premier centers for cancer care and research in children and adults. The Institute's staff increased from 150 at his arrival to 900 by the end of the decade.

For a generation of workers in the Longwood Medical Area, Tom Frei was a familiar sight, pedaling his bike to and from Dana-Farber. His sense of humor is legendary at Dana-Farber.

"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, MD, president of Dana-Farber from 1995 to 2000. "His was a massive contribution to medicine. Patients and trainees will remember him with deep respect."

Emil "Tom" Frei was born in St. Louis in 1924 and grew up surrounded by artists and musicians. His grandfather had started the Emil Frei Art Glass Company in St. Louis, specializing in the design and manufacture of stained-glass windows. This same 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.

Dr. Frei's interests took a turn for the scientific 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, Dr. Frei served under the V-12 Program until 1945. The U.S. Navy sent him to Colgate University for pre-medical 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, Dr. 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.

Dr. 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.

Dr. 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.


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