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High-Dose Chemotherapy for Advanced Germ-Cell Tumors

Two cycles of high-dose chemotherapy plus stem-cell rescue lengthened disease-free survival for some patients who relapsed after standard platinum-based chemotherapy.

The introduction of cisplatin-based chemotherapy in the 1970s dramatically improved the outcomes of men with advanced germ-cell tumors. Based on outcomes with this type of therapy, the International Consensus criteria classify patients with germ-cell tumors into good-, intermediate-, and poor-risk groups (J Clin Oncol 1997; 15:594). The cure rates for good- and intermediate-risk patients (80%–90% of all patients) are about 90% and 75%, respectively. Men who relapse after receiving initial cisplatin-based chemotherapy remain potentially curable with salvage regimens that include cisplatin, ifosfamide, and vinblastine or paclitaxel. High-dose chemotherapy with stem-cell rescue as either initial salvage after induction chemotherapy or secondary salvage after initial salvage relapse also provides a subset of patients with curative options (often with additional surgical resection).

Investigators from an Indiana cancer center retrospectively analyzed data from 184 patients with advanced germ-cell tumors who received high-dose chemotherapy and peripheral stem-cell rescue from 1996 through 2004. Patients who received high-dose chemotherapy as initial salvage treatment received standard doses of vinblastine plus ifosfamide plus cisplatin to reduce tumor bulk and to prevent progression while they awaited blood count recovery and high-dose second-line therapy. Patients who already had received ifosfamide-based salvage chemotherapy were offered high-dose chemotherapy without any further treatment.

High-dose chemotherapy consisted of two cycles of carboplatin (700 mg/m² of body-surface area) plus etoposide (750 mg/m²), each given intravenously at 5, 4, and 3 days before infusion of peripheral-blood stem cells. The second cycle of high-dose chemotherapy was not given if no response to cycle 1 was noted or if substantial nonhematologic toxicity occurred. Most patients who responded after two cycles of high-dose chemotherapy received daily oral maintenance doses of etoposide (50 mg/m²) for 21 consecutive days every 4 weeks for three cycles.

After a median follow-up of 48 months, 116 of 184 patients remained in complete remission. Of 135 patients who received the treatment as second-line therapy, 94 have been disease free during follow-up. Twenty-two of 49 patients who were treated with high-dose therapy in the third-line setting are long-term survivors, and, of 40 patients with cancer that was refractory to standard platinum-based therapy, 18 remained disease free. Three patients died during the peritransplant period from therapy-related complications, and three patients developed acute leukemia (2 died).

Comment: Three relatively small randomized trials of high-dose chemotherapy versus standard chemotherapy — one in the first-line setting in poor-risk patients (Journal Watch Oncology and Hematology Feb 5 2007) and two in the salvage setting (Journal Watch Oncology and Hematology Jul 25 2007 and Ann Oncol 2005; 16:1152) — failed to demonstrate a benefit for high-dose chemotherapy over conventional chemotherapy. This relatively large, albeit retrospective, series demonstrates that a subset of heavily treated, cisplatin-refractory patients with advanced germ-cell tumors can become long-term survivors after high-dose chemotherapy and stem-cell rescue.

— Robert Dreicer, MD, MS, FACP

Published in Journal Watch Oncology and Hematology July 25, 2007

Citation(s):

Einhorn LH et al. High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors. N Engl J Med 2007 Jul 26; 357:340-8.

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