INDIANAPOLIS—High-dose combination chemotherapy followed by autologous peripheral-blood stem cell transplant produced durable remissions in metastatic testicular cancer patients who relapsed or failed to respond to traditional therapy, according to a retrospective study from Indiana University School of Medicine (N Engl J Med 357:340-348, 2007).
Standard cisplatin-containing combination chemotherapy cures about 70% of patients with newly diagnosed metastatic germ-cell tumors. Researchers at Indiana—where the standard therapy was pioneered by Laurence H. Einhorn, MD—conducted a retrospective review of their high-dose treatment in 184 consecutive patients with metastatic testicular cancer treated from 1996 to 2004.
Study protocol
The team, led by Dr. Einhorn, professor of medicine at Indiana University's Melvin and Bren Simon Cancer Center, gave 173 patients two consecutive courses of high-dose chemotherapy consisting of carboplatin 700 mg/m2 plus etoposide 750 mg/m2 intravenously for 3 consecutive days. The chemotherapy was followed 3 days later by an infusion of peripheral-blood stem cells. The waiting period between the two courses was 3 to 4 weeks. The other 11 patients received a single course of the high-dose treatment. Most responding patients received a maintenance dose of oral etoposide 50 mg/m2 daily for 21 days every 4 weeks for three cycles.
Prior to receiving the high-dose therapy, 110 patients had cytoreduction with one or two courses of vinblastine plus ifosfamide plus cisplatin.
Disease-free outcomes
During a median follow-up of 48 months (range, 14 to 118 months), 116 patients (63%) were continuously disease free. Of these patients, 104 (90%) were disease free for more than 2 years. Six additional patients had complete remission of disease with further therapy, four after receiving paclitaxel plus gemcitabine (Gemzar) and two after undergoing subsequent resection of a germ-cell tumor.
Patient outcomes differed according to a number of prognostic factors that were significantly associated with progression-free survival.
Among the 135 patients who received the treatment as second-line therapy, 94 (70%) remained disease-free, compared with 22 (45%) of 49 patients who received the therapy as a third-line or later treatment. Of the 144 platinum-sensitive patients, 98 (68%) were disease free vs 18 (45%) of 40 patients with progressive metastatic disease who were refractory to the standard platinum-based treatment.
