N92 Sequential high-dose chemotherapy with hematopoietic stem-cell support in poor risk, relapsed or refractory germ-cell tumor patient treatment: Lithuanian experience

Poor-risk germ-cell tumors (GCT) represent significant challenges. Patients with poor-risk primary or relapsed GCT have been shown to benefit from high-dose chemotherapy (HDCT) with autologous stem cell support. In this paper we present our experience in using HDCT for poor prognosis primary, relapsed or refractory GCT at a single institution.

Primary advanced poor-risk nonseminoma, according to the International Germ Cell Cancer Collaborative Group (IGCCCG) criteria and GCT refractory to cisplatin based chemotherapy were included. Sequential etoposide (1.5 g/m²) cisplatin (100 mg/m²) and ifosfamide (10 g/m²) (VIP) regimen, followed by an infusion of autologous peripheral blood hematopoietic stem cells was used as a first line therapy. For salvage treatment paclitaxel (200 mg/m²) and ifosfamide (6 g/m²) (TICE) followed by sequential carboplatin (AUC24) and etoposide (1.2 g/m²) were used. The data were reviewed retrospectively. Decline in tumor marker levels, tumor response, treatment toxicity and survival were evaluated.

From January 2004 to May 2009, 12 GCT patients (6 primary poor-risk GCT and 4 cisplatin refractory patients) were included. For 2 patients no data were available. Median age was 25.2 (17–35) years. Five patients had testicular primaries while another five presented with primary extragonadal tumor. Four of 5 patients underwent primary orchofuniculectomy, and all were managed with retroperitoneal lymph node dissection (RPLND) of residual disease. In one patient with initially high disease burden orchofuniculectomy was performed after chemotherapy. Three of 5 patients with mediastinal primaries underwent thoracotomy. 6 patients with primary GCT received VIP treatment. 3 relapsed and 1 refractory cases were treated with TICE protocol. 2 primary patients progressed after VIP and received second line treatment with TICE. Eight patients had elevated both AFP and β-HCG. After primary treatment, 8 of 12 patients had partial responses (PR), 1 had stable disease (SD) and 1 had progressive disease (PD). Pretreatment tumor markers decreased in all 9 patients with SD or PR but remained elevated in the refractory case. Chemotherapy related toxicity was acceptable, with grades III-IV thrombocytopenia (100%) and febrile neutropenia being the most prevalent (58%). Median follow up was 26.2 months. Overall survival was 66.7% and progression free survival was 58.3%. Eight out of 12 patients are alive and 7 are disease free. Two patients died from treatment toxicity, one from progression of disease, one from secondary acute leukemia.

HDCT is feasible and effective with acceptable toxicity in patients with poor risk primary and relapsed GCTs. Surgery remains an important part of any strategy.