BACKGROUND: In the late Nineties the use of high-dose chemotherapy (HDCT) and stem cell rescue held promise for patients with advanced and poor prognosis germ cell tumors (GCT).
We started a randomized phase 2 trial to assess the efficacy of sequential HDCT compared to cisplatin, etoposide, and bleomycin (PEB).
PATIENTS AND METHODS: Patients were randomly assigned to receive 4 cycles of PEB every 3 weeks or 2 cycles of PEB followed by a high-dose sequence (HDS) comprising HD-cyclophosphamide (7.0 g/m2), 2 courses of cisplatin and HD-etoposide (2.4 g/m2) with stem cell support, and a single course of HD-carboplatin (AUC 27 mg/ml x min) with autologous stem cell transplant. Postchemotherapy surgery was planned on responding residual disease in both arms. The primary endpoint was progression-free survival (PFS). The study was designed to detect a 30% improvement of 5-year PFS (from 40 to 70%), with 80% power and two-sided α at 5%.
RESULTS: From 12/1996 to 03/2007, 85 patients were randomized: 43 in PEB and 42 in HDS arm. Median follow up was 114.2 months (IQR: 87.7-165.8). Complete (CR) or partial response with normal markers (PRm-) were obtained in 28 (65.1%) and 29 (69.1%) patients, respectively. Five-year PFS was 55.8% (95%CI, 42.8-72.8) and 54.8% (95%CI, 41.6-72.1%) in PEB and HDS arm, respectively (logrank test p=0.726). Five-year overall survival (OS) was 62.8% (95%CI, 49.9-79.0) and 59.3% (95%CI, 46.1-76.3). One toxic death (PEB arm) was recorded.
CONCLUSIONS: The study failed to meet the primary endpoint. Furthermore, survival estimates of conventional dose chemotherapy higher than expected should be accounted for and will likely limit further improvements in the first-line setting.
Written by:
Necchi A, Mariani L, Di Nicola M, Lo Vullo S, Nicolai N, Giannatempo P, Raggi D, Farè E, Magni M, Piva L, Matteucci P, Catanzaro M, Biasoni D, Torelli T, Stagni S, Bengala C, Barone C, Schiavetto I, Siena S, Carlo-Stella C, Pizzocaro G, Salvioni R, Gianni AM. Are you the author?
Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy; Clinical Epidemiology and Trials Organization Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy; Department of Surgery, Urology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy; Ospedale Misericordia, Grosseto, Italy; Oncologia Medica ASL TO5 Ospedale di Carmagnola, Torino, Italy; Niguarda Cancer Center, Ospedale Niguarda Ca' Granda, Milano, Italy; Department of Oncology and Hematology, Humanitas Cancer Center, Humanitas Clinical and Reseach Center, Rozzano, Italy; Department of Medical Biotechnology and Translational Medicine, University of Milano, Milano, Italy; Department of Pathophysiology and Transplantation, University of Milano, Milano, Italy.
Reference: Ann Oncol. 2014 Oct 24. pii: mdu485.
doi: 10.1093/annonc/mdu485
PubMed Abstract
PMID: 25344361