Poor-Prognosis Germ Cell Tumors: We Have Not Yet Crossed The Finish Line

Main Category: Urology / Nephrology
Also Included In: Cancer / Oncology
Article Date: 19 Feb 2007 - 10:00 PDT

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UroToday.com- Despite the dramatic impact of cisplatin-based chemotherapy on the treatment of testicular cancer as a whole, a small percentage of patients with high-risk tumors will fail first-line chemotherapy and carry a measurable cancer-specific mortality. Despite the use of salvage high dose chemotherapy with stem cell rescue, the 5-year survival of intermediate and high-risk tumors continues to be approximately 80% and 50%, respectively. Should these high-risk patients with receive more aggressive treatment as first-line therapy?

In the January 20th issue of the JCO, Motzer et al report results from a Phase III multi-institutional study designed to determine whether high dose chemotherapy with stem cell rescue results in a survival advantage as first-line therapy for men with high risk testicular cancer. The objective of the study was to bring the current standard of care for "last-line" therapy for refractory tumors to the forefront in patients with high risk tumors.

The study was designed as a prospective, randomized trial where previously untreated men with intermediate or high-risk metastatic testis cancer received either standard chemotherapy (4 cycles of BEP) or 2 cycles of BEP followed by 2 cycles of high dose chemotherapy with carboplatin, etoposide, and cyclophosphamide and autologous stem cell rescue on day 5. Testicular cancer risk was based on the International Germ Cell Cancer Collaborative Group criteria.

Two hundred and nineteen patients were randomized into 2 groups. After 1 year, patients in the BEPx4 group exhibited a complete response rate of 48% compared with 52% in patients who received BEPx2 plus high dose chemotherapy. This difference was not statistically significant. As previously reported in other studies, a faster rate of AFP and beta-hcg marker decline in the first months of chemotherapy correlated with improved disease-specific survival 1 and 2 years after therapy. The 1-year durable complete response for those patients with a slow marker decline was 61% for patients in the high dose chemotherapy group versus 34% in the BEPx4 arm.

This well conducted study suggests that high dose chemotherapy does not offer a survival advantage over standard chemotherapy in the treatment of patients with high risk tumors. Most importantly, these data validate the role of early serum tumor marker decline in predicting patient response to chemotherapy. Patients with a sluggish pattern of marker decline during their early phase of treatment may be selected for novel investigational protocols.

David J. Vaughn and Edward A. Stadtmauer
J Clin Oncol. 2007 Jan 20; 25(3):239-40.

Reviewed by UroToday.com Contributing Editor Ricardo F. Sánchez-Ortiz, MD

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