To mark its 50th anniversary, the American Society of Clinical Oncology (ASCO) invited physicians, patients, and the public to name the most important advances in clinical cancer research in the past half century. From more than 2,000 responses, the top choice was a cure for advanced Hodgkin lymphoma developed by scientists at the National Cancer Institute in the mid-1960s. The treatment used a combination of chemotherapy agents known by the acronym MOPP and represented the first time that combination chemotherapy had cured a non-leukemic solid tumor in adults. Its success led to the development of other combinations of chemotherapy drugs that revolutionized the treatment of malignancies ranging from testicular cancer to breast cancer.
One of the five members of the NCI team that worked on the MOPP program was George Canellos, MD, a young scientist and clinician who went on to become the Chief of Medical Oncology at Dana-Farber. Now a senior physician at Dana-Farber, he is also the William Rosenberg Professor of Medicine at Harvard Medical School.
We recently sat down with Canellos to discuss the origin of MOPP and its impact on cancer treatment.
What was the standard treatment for advanced Hodgkin lymphoma prior to MOPP?
Radiation therapy was used if the disease was localized to one area. There were also several chemotherapy drugs that produced brief remissions. Patients would be treated with one drug, and, when it stopped working, would receive another. With both radiation therapy and chemotherapy, relapses were inevitable. The cure rate for advanced disease was essentially zero.
What was the inspiration for MOPP?
Studies were beginning to show that childhood leukemia could be cured by combination chemotherapy. Some drugs were known to be active against Hodgkin lymphoma, if only temporarily, so it was decided to test a combination of them in patients with advanced disease. The initial drugs in this group were mustragen (also known as nitrogen mustard), oncovin (also known as Vincristine), methotrexate, and prednisone (a steroid that reduces inflammation). This treatment was known by the acronym MOMP. Later, Procarbazine was substituted for Methotrexate – hence the designation MOPP.
Many of the patients who participated in the initial trials of MOPP were from rural West Virginia, and didn’t have access to urban treatment centers. The trials were conducted on the NCI campus in Maryland, with the government paying for participants’ transportation and lodging.
Who was on the NCI team doing the research?
The group was led by Vincent DeVita Jr., MD, who was the inspiration for MOPP and went on to become director of the NCI and, subsequently, the Yale Cancer Center. In addition to me, the team included Bruce Chabner, MD, now of Massachusetts General Hospital; Robert Young, MD, who became president of Fox Chase Cancer Center; and Philip Schein, MD, who later served as president of ASCO.
What were the results of the MOPP trial?
In many patients, the disease went away and stayed away, although the side effects were often harsh. Follow-up studies showed that more than 10 years after treatment, 70 to 80 percent of patients were still alive and free of disease. In 1970, we published a paper showing, for the first time, that it was possible to cure patients with advanced disease who had relapsed after radiation therapy.
How did the findings affect the direction of cancer research?
We extended our findings by substituting the drug cyclophasphamide for nitrogen mustard for the treatment of large-cell lymphoma. A significant fraction of patients were cured with this regimen. It was revolutionary at the time. We also developed the first successful drug combination for the treatment of advanced breast cancer.
The work was the impetus for the development of chemotherapy combinations for a wide range of cancers. It’s arguable that our work led to the official acceptance of medical oncology [the field of cancer treatment with medications] by the American Board of Internal Medicine as a distinct subspecialty.