Bevacizumab/High-Dose Chemotherapy with Autologous Stem-Cell Transplant for Poor-Risk Relapsed or Refractory Germ-Cell Tumors
Mené sur 43 patients atteints d'une tumeur germinale de stade avancé et réfractaire (âge moyen : 30 ans), cet essai évalue l'efficacité, du point de vue de la survie sans récidive à 2 ans, et la toxicité d'un traitement combinant bévacizumab et une chimiothérapie à haute dose
Background : High-dose chemotherapy (HDC) using sequential cycles of carboplatin/etoposide is curative for relapsed germ-cell tumors (GCT). However, outcomes of high-risk patients in advanced relapse remain poor. We previously developed a new HDC regimen combining infusional gemcitabine with docetaxel/melphalan/carboplatin (GemDMC), with preliminary high activity in refractory GCT. Given the high vascular endothelial growth factor expression in metastatic GCT and the synergy between bevacizumab and chemotherapy, we studied concurrent bevacizumab and sequential HDC using GemDMC and ifosfamide/carboplatin/etoposide (ICE) in patients with poor-risk relapsed or refractory disease. Patients and Methods : Eligibility criteria included intermediate/high-risk relapse (Beyer Model), serum creatinine ²1.8 mg/dL and adequate pulmonary/cardiac/hepatic function. Patients received sequential HDC cycles with bevacizumab preceding GemDMC (cycle 1) and ICE (cycle 2). The trial was powered to distinguish a target 50% 2-yr relapse-free survival (RFS) from an expected 25% 2-year RFS in this population. Results : We enrolled 43 male pts, median age 30 (20-49), with absolute refractory (N=20), refractory (N=17) or cisplatin-sensitive (N=6) disease, after a median 3 (1-5) prior relapses. Disease status right before HDC was unresponsive (N=24, progressive disease 22, stable disease 2), partial response with positive markers (PRm+) (N=8), PRm− (N=7) or complete response (N=4). Main toxicities were mucositis and renal. Four patients (three with baseline marginal renal function) died from HDC-related complications. Tumor markers normalized in 85% patients. Resection of residual lesions (N=12) showed necrosis (N=4), mature teratoma (N=2), necrosis/teratoma (N=2) and viable tumor (N=4). At median follow-up of 46 (9-84) months, the RFS and overall survival rates are 55.8% and 58.1%, respectively. Conclusions : Sequential bevacizumab/GemDMCÐbevacizumab/ICE shows encouraging outcomes in heavily pretreated and refractory GCT, exceeding the results expected in this difficult to treat population.This trial was registered with ClinicalTrials.gov, No. NCT00936936.