High-dose sequential chemotherapy versus conventional-dose chemotherapy as first-line treatment for advanced poor prognosis germ-cell tumors
A multicenter phase III Italian trial did not show improvement in treatment outcomes
Upfront high-dose chemotherapy for poor prognosis germ-cell tumors (GCTs) showed promising results in preliminary studies. A group of Italian researchers led by Dr Massimo Di Nicola of the Medical Oncology Department, Istituto Nazionale Tumori, Milan, presented this week at the AIOM 11th National Congress of Medical Oncology results from 89 patients randomized between high-dose sequential chemotherapy (HDS) followed by autologous hematopoietic stem-cell transplant (ASCT), and standard chemotherapy (CT). Results were also presented during the proffered papers session at the ECCO 15 – ESMO 34 Congress in Berlin (September 2009).
Poor IGCCCG prognosis GCT patients were randomly assigned to receive 4 cycles of PEB (cisplatin, etoposide, bleomycin) (arm A) or 2 cycles of PEB followed by a sequence of high-dose (HD) cyclophosphamide, 2 courses of PEB with HD-VP16 and HD-carboplatin rescued by ASCT (arm B). In both arms, post-chemotherapy surgery was planned for residual resectable mass. Primary endpoint (EP) was 2-years overall survival. Investigators planned to accrue 50 patients/arm to detect a 20% improvement in patients receiving HDS. Owing to the prolonged accrual time and the results of interim analysis, the study was stopped early.
From December 1996 to April 2007, 89 patients were randomized: 46 in arm A and 43 in arm B. A total of 84 patients (94%) were evaluable for response and outcome (43/41), while 41 (95%) and 36 (88%) patients completed the program. Median follow-up was 50 months (range 1-129). In an intent-to-treat analysis, major responses [complete responses (CR) + partial responses with normal markers (PRm-)] were 31 (67%) after PEB ± surgery while 30 (70%) after HDS ± surgery. Overall- and progression-free survival at 2-years were not significantly different. Similar number of patients relapsed/progressed in each group, and numbers were also similar for patients who have been rescued by further conventional-dose salvages. Progressions occurred within a median time of 4 and 5.5 months, respectively. Mean administered CDDP dose-intensity was significantly different between the 2 arms (p<0.0001). There was one treatment-related death in the arm A.
The authors did not observe differences in primary study endpoints and underlined a need for novel treatment strategies in this group of patients.
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