1. Samson, Kurt

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Gianni Bonadonna, MD, whose revolutionary research in combination adjuvant chemotherapy helped transform the treatment of both breast cancer and Hodgkin lymphoma, died Sept. 7, in Italy, at the age of 81.

Figure. Gianni Bonad... - Click to enlarge in new windowFigure. Gianni Bonadonna, MD (1934-2015)

His research has helped reduce morbidity and mortality for millions of patients after introducing adjuvant therapy at a time when radiotherapy and radical mastectomies were standard practice.


A widely revered, beloved, charismatic, and internationally acclaimed investigator, Bonadonna published over 550 papers and received numerous awards for his revolutionizing work. Until his death he chaired the Committee on Prospective Clinical Trials at the Istituto Nazionale dei Tumori in Milan.


Although his early findings on the potential of early adjuvant therapies were not initially embraced by the oncology community in general, in the decades since, his and others' research helped establish combination regimens that are today considered the optimal approach for treating many of these cancers.


In 1972, Dr. Bonadonna and his colleagues published preliminary findings in early trials among Hodgkin's patients at Italian institute using a new combination chemotherapy regimen called ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and dacarbazine). They determined that ABVD was more effective than the MOPP regimen (mustargen, oncovin, procarbazine, and prednisone), then the standard combination.


Developed in the 1960s at the U.S. National Cancer Institute by researchers that included Vincent T. DeVita, Jr., MD. MOPP was the first combination chemotherapy regimen to result in high success rates in Hodgkin's disease and other blood cancers.


In 1973, Bonadonna and his colleagues published a groundbreaking study in the New England Journal of Medicine that demonstrated the effectiveness of combined chemotherapy using CMF (cyclophosphamide, methotrexate, and fluorouracil) for node-positive operable breast cancer. This was then confirmed in a 30-year follow-up review of treated breast cancer cases, published in 2005. That study showed that CMF, especially with the addition of prednisone (CMFP) significantly reduced the risk of recurrence and death.


Vincent DeVita

In an interview, DeVita, Director of the National Cancer Institute from 1980 to 1988 and now the Amy and Joseph Perella Professor of Medicine and Medical Oncology at Yale Cancer Center, remembered working with Bonadonna in the early years: "I first met him when he spent a week with us at the NCI Medicine Branch in 1969 going over the CMF protocol we had developed and modifying it for use as adjuvant chemotherapy in breast cancer.


"No one in this country would touch it at the time, but Gianni adopted it and ran the trial in Italy, with the NCI providing support. That 1976 trial, published in NEJM, rocketed him to fame."


George Canellos

George P. Canellos, MD, the William Rosenberg Professor of Medicine at Harvard Medical School, who practices at Dana-Farber Cancer Institute, also recalled those days. At the time he was a clinical associate at the NCI, and from 1975 to 1995, he was Chief of Dana-Farber's Division of Medical Oncology; a former Editor-in-Chief of the Journal of Clinical Oncology and a past president of the American Society of Clinical Oncology, Canellos is currently a senior physician at Dana-Farber and Brigham and Women's Hospital, and was a major figure in the emerging field of adjuvant treatment while a visiting investigator in Milan.


"I first got to know Dr. Bonadonna when he came to the National Institutes of Health to see if the NCI was involved with adjuvant therapy for breast cancer. Indeed, we were in the process of completing a trial of combination chemotherapy for metastatic breast cancer in previously untreated women."


Bonadonna's proposed regimen of CMF and then CMFP was found to be very active in achieving remission of disease, Canellos said. "Dr. DeVita and I were in the process of compiling our data for review by the leadership and we hoped to use it to keep early breast cancer from metastasizing. At that time, however, the centers and other U.S. oncology groups were reluctant to participate."


Today, adjuvant chemotherapy is a standard practice in treating breast cancer recurrence and metastases in many women undergoing therapy.


The Early Years

Gianni Bonadonna was born on July 28, 1934, in Milan. After he graduated from the University of Milan in 1959 with a degree in Medicine and Surgery he studied in the U.S. between 1961 and 1964. During his postdoctoral training from 1961 to 1964 he was a research fellow at Memorial Sloan Kettering Cancer Center, in New York. After returning to Italy he joined the Istituto Nazionale dei Tumori of Milano, where he stayed for the rest of his life. In 1976 he became the Director of Medical Oncology and in 1991 became the Head of Cancer Medicine at the Milan institute.


His work in adjuvent therapy for breast cancer and Hodgkin's disease included the first trials of doxurubicin, bleomycin, and epirubicin. In subsequent years he was awarded many national and international honors.


Breast Cancer Award and Lecture

In recognition of his many contributions to cancer treatment, the American Society of Clinical Oncology in 2007 established the "Gianni Bonadonna Breast Cancer Award and Lecture."


In announcing the creation of that award, ASCO then-President Gabriel Hortobagyi, MD, Professor of Medicine, in the Department of Breast Medical Oncology, the Nellie B. Connally Chair in Breast Cancer, and Program Director of the Susan G. Komen Interdisciplinary Breast Fellowship Program at the University of Texas MD Anderson Cancer Center, praised Dr. Bonadonna's many contributions to the field of breast cancer treatment: "Without Gianni Bonadonna's initial work in demonstrating the activity of chemotherapy, we would not be where we are today in terms of the management and the cure of breast cancer," he said.


"Bonadonna's legacy is one of focus, persistence, passion, innovation, and creativity. That's a tall order for most new members of our profession but clearly is a combination of attributes that make Dr. Gianni Bonadonna a role model for oncology professionals of the future."


Hodgkin's Disease Award and Lecture

His contributions to research in the field of Hodgkin lymphomas also was acknowledged by the Committee of the International Symposium on Hodgkin's lymphoma in Cologne, Germany, where the organization created the "Gianni Bonadonna Hodgkin's Disease Award and Lecture."


Over the course of his professional career, in addition to his many research papers, he also wrote books aimed at lay readers, as well as a book on the Sepoy revolt in India, a rebellion in 1857 against the army of the East India Company, regarded as India's first war of independence.


Unorthodox and Dedicated

In the interview with OT, Canellos also talked about Bonadonna's many interests outside of his research pursuits: "Dr. Bonadonna was a very eclectic physician who enjoyed traveling to exotic places. He collected objects of art resulting in his home being almost a museum in itself."


Similarly, DeVita said that by enthusiastically collaborating with other researchers around the world, Bonadonna gave breast cancer and Hodgkin's disease what essentially amounted to a treatment makeover, and not just in terms of investigating adjuvant therapies: "He changed the practice of medical oncology in Italy by doing things they had not done before, like telling patients their diagnosis, and that CMF and CMFP were experimental treatments and asking patients for their informed consent. He also adopted rigorous precepts for clinical trials. This took a great deal of courage on his part, but paid off handsomely for Italian cancer patients."


Bonadonna suffered a serious stroke in 1995, but continued to work toward improving treatment and practice. "He showed a different kind of courage; the courage of a severely disabled patient to continue to lead a productive life as founder and president of the Fondazione Michelangelo, remarking that with his disabilities he was better able to understand the pain his patients were experiencing," DeVita said. "His approach to life in the face of adversity was an inspiration to us all.


"He was a good friend, and I always enjoyed his company. We shared a love of opera and were both always reduced to tears by Puccini's music during the last 12 minutes of the first act of La Boheme. I will miss him."


Matthew Ellis's Bonadonna Award Lecture

Matthew Ellis, MD, BChir, PhD, is this year's recipient of the Gianni Bonadonna Breast Cancer Award, an honor bestowed last month at the Breast Cancer Symposium. Read a summary of his award lecture here, online ahead of print: