Salvage Chemotherapy for Poor Prognosis Germ Cell Tumors
Status:
Unknown status
Trial end date:
2020-09-01
Target enrollment:
Participant gender:
Summary
High-dose chemotherapy with autologous hematopoietic stem-cell transplantation is a standard
salvage treatment used in adults with germ cell tumors (Einhorn et al, J Clin Oncol 2007).
Disease prognosis following 1 to 2 intensified combinations of etoposide - carboplatin +/-
ifosfamide depends on the patient's performance status (PS) at inclusion and the prior
sensitivity of the disease to cisplatin. A poor PS and/or being refractory to cisplatin
suggest a higher toxicity and a bad prognosis.
However, predictive factors of response to high-dose chemotherapy do not include a
chemo-sensitivity phase with a semi-intensive chemotherapy excluding a platinum compound
(epirubicin - paclitaxel), which still allows stem-cell harvest. The use of this chemotherapy
combination induced a response in more than one third of the patients treated during disease
progression in the TAXIF I study. The same strategy was tested in the TAXIF II study, which
completed the inclusion of 45 patients and was closed in May 2008. Results of the TAXIF II
study, are currently being analyzed; they support the hypothesis to prioritarily treat
patients with a sensitive relapsed disease at the time of the high-dose administration.
A combination of a semi-intensive sequential ICE type chemotherapy plus bevacizumab was used
on a highly refractory patient. A 5 months nearly complete response was achieved. Indeed, the
overexpression of VEGF (Vascular Endothelial Growth Factor) has been identified as an
independent risk factor in patients with germ cell tumor. Therefore, a treatment strategy
using an inductive chemotherapy followed, in case of response, by a double intensification
therapy in combination with a VEGF treatment, could be an interesting approach in patients
with poor prognosis germ cell tumors.
The aim of this phase I/II trial is to assess the feasibility of a Bevacizumab - ICE
(Ifosfamide-Carboplatin-Etoposide) high dose combination with the support of autologous
hematopoietic stem cell for two intensive consecutive cycles ("tandem" intensification) in
patients with a poor prognosis germ cell tumor non refractory to a front-line mobilization
chemotherapy using two half intensified consecutive combinations of Epirubicin-Paclitaxel.