Friday, August 1, 2014

Classic Manuscript in Urology: Einhorn and Donohue. Journal of Urology, 1977.

Lawrence Einhorn, MD
In the 1960's, metastatic testicular cancer was a death sentence - with a greater than 90% mortality within 1 year of diagnosis.  In 1965,  cisplatinum  chemotherapy was discovered by Dr. Rosenberg at Michigan State University.[47] The drug was tried in testicular cancer in 1971, with a number of complete responses to treatment but with terrible side effects including permanent renal failure.[49]  Shortly thereafter, Drs. Einhorn and Donahue added cisplatinum to the combination of vinblastine and bleomycin, a chemotherapy with some known efficacy in testicular cancer.  The results were astounding - the cure rate went from 10% to 70% and the treatment of testicular cancer was changed forever.

Einhorn LH, Donohue JP.  Improved chemotherapy in disseminated testicular cancer.  J Urol. 1977 Jan;117(1):65-9.
Journal of Urology.

In this manuscript, Drs. Einhorn and Donohue describe their initial experience with a platinum-based regimen for the treatment of metastatic testis cancer.  Twenty-seven patients received either a regimen of adriamycin, bleomycin and vincristine or platinum, vinblastine and bleomycin (PVB).  The patients receiving PVB had an outstanding response with 16 of 21 (76%) achieving a complete response (no visible cancer), 4 (20%) with a partial response and only 1 with no response.  Considering all patients treated by Dr. Einhorn during this time period, complete remission was achieved with PVB chemotherapy alone in 85% and 93% with additional surgery.

Unfortunately, the response was not durable in all patients. In the manuscript, Dr. Einhorn speculates in the discussion,
"Although we do not have long-term followup data on any of our patients treated with [PVB], it seems quite reasonable to expect at least 50 percent of our patients in complete remission will have cures..."
In fact, the durable cure rate was closer to 70% -- a logarithmic increase in the survival for men with advanced germ cell tumors!

Another important point from this paper was that the "Einhorn Regimen" involved more than just PVB.  By hydrating patients with copious fluids, Dr. Einhorn mitigated many of the toxicities, including nephrotoxicity.  Shortly after this publication, Dr. Einhorn would work to design, implement and add antiemetics to the regimen.  The results were so impressive the FDA (Food & Drug Administration) approved the "Einhorn Regimen" for advanced testicular cancer without any further studies.

Take home: Metastatic testis cancer was fatal in nearly all patients before this study.  Careful selection of chemotherapeutic agents based on mechanistic principles changed the paradigm for testis cancer (and many other malignancies).  Attention to side effect profiles and adjuvant therapies to mitigate side effects can improve outcomes in patients receiving cytotoxic chemotherapy.

Classic Manuscripts in Urology will be posted on this blog on regular basis.  These articles are meant to highlight the achievements of our predecessors, recognize the work from which we build our careers and stimulate new conversations and discussion on a variety of urological topics.  Please feel free to comment on this manuscript, help point out its strengths and weaknesses, or suggest a new manuscript and topic. 


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