Testicular Cancer: Changing Tides

Prior to 1974, localized testicular cancer was easily cured with orchiectomy, while metastatic disease was effectively a death warrant – cure rates were as low as 5% with a variety of chemotherapeutic agents. This trial, conducted by an up-and-coming researcher using an experimental drug called cis-diamminedichloroplatinum (or as we know it, cisplatin), provided a much-needed win in the battle against solid cancers. From 1974-1976, Lawrence Einhorn used a combination of cisplatin, vinblastine and bleomycin to treat patients with mild to severe metastatic disease. Some patients received adjunct surgery to remove residual tumors. Overall, at the time of publication, 38 of 47 patients were disease free. Moreover, at 13-year follow-up (which is remarkable in and of itself), over 50% of patients were disease free, an achievement stated as a “one-log increase in the cure rate.”

In addition to improved cure rates, cisplatin did not cause a pronounced myelosuppression like other chemotherapeutic drugs. It was not without its vices though. As Einhorn described, platinum had toxic effects on the kidney, manifested as a 25-50% reduction in baseline creatinine clearance. This was likely exacerbated by the dehydration caused by the intractable nausea and vomiting, which is eloquently described in Mukherjee’s Emperor of All Maladies. From a critical perspective, the study was well conducted in the context of a limited number of patients. Criteria for partial versus complete remission were well-defined, and follow-up was more than sufficient. Additional trials in the following years would cement the new findings.

Although partial results had been published in reports in Journal of Urology and American Family Physician, the complete results of the trial were ultimately published in Annals of Internal Medicine in 1977.  Given the overwhelmingly positive response to the therapy and the aggressive nature of non-seminomatous testicular cancer, it was quickly approved by the FDA in 1978 and became the standard of care. The combination chemotherapy was modified in the 80s to use etoposide instead of vinblastine, leading to additional improvements in cure rates. That same combination is in use today, and cure rates exceed 95%. Moments like this, when one can claim a logarithmic increase in cure rates, are few and far between in medicine.

Einhorn LH, Donohue J. Cis-diamminedichloroplatinum, vinblastine, and bleomycin combination chemotherapy in disseminated testicular cancer. Ann Intern Med. 1977. Sep;87(3):293-8.

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