Phase 2 trial of high-dose chemotherapy in patients with disseminated germ-cell tumours
Thursday, 2 July 2009- High-dose chemotherapy (HDCT) using the etoposide-carboplatin ± ifosfamide regimen is able to circumvent resistance in germ-cell tumour (GCT) patients (pts), even when used as third-line or later therapy (Lotz, Ann Onco.l 2005 / Einhorn, N Eng J Med. 2007).
Lead author J.Lotz and his colleagues presented the phase 2 findings of HDCT in patients with disseminated germ-cell tumours during a poster session at the ASCO Annual Meeting in Florida, USA.
The researchers said patients whose relapses occur more than 4 weeks after CDDP-based CT are probably the best candidates for HDCT. Epirubicine (E) and paclitaxel (P) possess interesting activity in GCTs. Thiotepa (TTP) and P can be safely combined at high dose with good efficacy. The ICE regimen is a well-known worldwide used regimen.
Non-resistant/refractory GCTs pts failing CT and with adverse prognostic factors were planned to receive 2 cycles combining (mg/m²) E (100) and P (250), given on day 1 and 14 supported by filgrastim (F), followed by 3 consecutive HDCTs [1 course combining a 3-d combination of P (360) + TTP (720), followed by 2 ICE regimens (IFM, 12 g/m², CBDCA, AUC 20, VP16, 1,500 mg/m²), given on 5 days with HSCT and F]. Inclusion criterias were mainly: radiologically and/or biologically mesurable disease, seminomatous GCT in relapse after 2 lines of CT (BEP/VeIP), non-seminomatous GCT in relapse after 1 or 2 lines of CT or in PR after 1 line of CT, primary mediastinal GCT in first relapse. Resistant / refractory pts were excluded. PBSC were collected after the first ± the second courses of EP (aim: 9x10E6 CD34+/kg BW). We report herein on the preliminary results of this multicentric study.
From September 2004 to December 2007, 45 pre-treated (BEP ± VeIP) pts with gonadal (89%) or extra-gonadal T (11%) were treated in second-line (27%), 3rd-line (44 %) or more (29 %). Thirty-five pts received 1 HDCT, 29 two HDCTs and 21 pts could receive the whole protocol. At the time of analysis (12/08), the final overall response rate was 47%, 10 pts were in continuous CR (median time, 8 m; range, 1-18), and 37 pts (82%) were alive at a median F/U of 9 m (range, 1-26). The 1-y survival rate was 90%. The 1-y PFS rate was 62%. One pt died of multi-organ failure and 7 died of disease progression.
The researchers concluded that this HDCT program preceded by two semi-intensive cycles of E-P is highly effective in non-resistant/refractory pts with disseminated GCTS failing CT and with adverse prognostic factors.
Source: J. Lotz, F. Selle, K. Fizazi, et al., “A phase II trial of high-dose chemotherapy (HDCT) supported by haematopoietic stem cell transplantation (HSCT) in patients (pts) with disseminated germ-cell tumours (GCTs) failing chemotherapy and with adverse prognostic factors: The TAXIF II protocol,” Poster Discussion, ASCO Annual Meeting, Florida, USA; J Clin Oncol 27:15s, 2009 (suppl; abstr 5028)
