How Einhorn Helped Turn a Deadly Cancer Into a Curable Disease
The “Giants of Cancer Care” awards program, which the Intellisphere® Oncology Specialty Group launched last year, honors oncology specialists whose work has made a significant impact on the lives of patients with cancer. Lawrence H. Einhorn, MD, was recognized for developing an innovative treatment for testicular cancer that has dramatically improved outcomes for men diagnosed with the disease.
By adding a single agent to a fledgling treatment regimen, Lawrence H. Einhorn, MD, transformed testicular cancer from a methodical killer of young men into a highly curable condition for many patients, including famed cyclist Lance Armstrong, whom Einhorn treated.
The medical oncologist had been on the faculty at Indiana University (IU) for only a year when he read about a promising early trial of cisplatin for the treatment of testicular cancer. He thought it would make sense to add the metal to a regimen that had also demonstrated some success in treating the disease: bleomycin and vinblastine.
“We did a phase II study in 1974, when the cure rate for metastatic testicular cancer in patients in their 20s and 30s was 5% to 10%,” recalled Einhorn, now 71. “In my youthful exuberance, I was hoping the cure rate would go to 15% or 20%, but over 70% of study participants achieved complete remissions, all but 10% of them lasting.
It’s not often that the FDA will approve a drug based on a nonrandomized, single-institution study. In this case, the results were so profound that it was hard not to be solidly convinced.”
In the 40 years since, Einhorn, now a distinguished professor and Livestrong Foundation Professor of Oncology at the IU School of Medicine, has driven other major advances in the treatment of testicular cancer, coming up with a more effective and less toxic standard regimen and revealing important principles that are being applied to the treatment of other cancer types. At the same time, he has helped develop new treatment strategies for small cell lung cancer.
A Life-Changing DiscoveryEinhorn’s goal upon arriving at IU was to study cancers that were already somewhat responsive to chemotherapy, so that small changes in treatment might lead to big improvements in outcome.
In addition to small cell lung cancer, he focused on testicular cancer, initially using the regimen of doxorubicin, bleomycin, and vinblastine that had been developed for other applications at The University of Texas MD Anderson Cancer Center in Houston, where he had recently completed a fellowship.
Although the combination was useful, Einhorn was looking for something still more effective when, in 1974, he learned of a phase I trial of single-agent cisplatin that had sparked brief remissions in patients with testicular cancer who had previously been treated with chemotherapy. He thought the drug would work well with bleomycin and vinblastine, a pairing that was also developed at MD Anderson, in this case specifically for patients with testicular cancer.
“In 1974 or 2013, the principles of putting drugs together are the same,” Einhorn said. “The drugs in the recipe all should have single-agent activity against cancer, different mechanisms, and different types of side effects. You need evidence of a synergistic effect that can be demonstrated in the lab, as was the case with vinblastine and bleomycin, and later with platinum and other drugs.”
At the time, cisplatin was being used in cancers with no standard therapies, after patients had failed other regimens; however, it caused nausea, vomiting, numbness and tingling in the legs, kidney problems, and ringing in the ears before it could do much to fight disease.
Einhorn “figured out how to get around that” by hydrating patients with IV fluids before and during treatment, preventing accumulation of platinum in the kidneys. He also collaborated with pharmaceutical companies to study drugs that could work as antiemetics, including the first-in-class 5HT3 receptor antagonist ondansetron.
Those work-arounds, and cisplatin’s success in treating testicular cancer, saved the heavy metal from extinction as a medical treatment, Einhorn said. “Here we are 40 years later, and platinum is used in first-line chemotherapy for 10 different diseases,” he said. “It’s used more widely in more diseases than any single cancer drug, yet it almost never made it out of the gate.” Einhorn’s trifecta with the regimen is a reminder, he said, that other landmark treatments may be waiting in the wings as investigators research new drugs, such as molecularly targeted agents, to treat cancer.