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Though eighty percent of advanced germ cell tumors (GCTs) could be cured to date, only 20–30% of patients with chemotherapy refractory or resistant GCTs, so called ‘difficult-to-treat’ GCTs would remain continuously disease-free with salvage chemotherapy or surgery. International classification gave us to the information about induction and second-line chemotherapy, however, the optimal salvage chemotherapy remains unclear. In this session, we will review literatures and present our sequential chemotherapy strategy for advanced GCTs.

Patients and methods

Two hundred sixteen patients with advanced GCTs treated at Kyoto Prefectural University of Medicine from June 1998 to December 2011 were retrospectively assessed.


Median age was 32 years (range: 17–68 years). Non-seminoma was in 181 cases (83.8%), regarding primary histology. IGCCC showed good in 94 cases (45.2%), intermediate 58 (27.9%), poor 56 (26.9%). As the induction therapy, BEP therapy was carried out in 190 cases (88.0%). Salvage chemotherapy was done for 121 cases. As the second-line therapy, VIP/VeIP and TIP/N therapy were done in 42 (34.7%) and 41 cases (33.8%), respectively. Regarding the patients requiring third line or more chemotherapy, 90, 61, 39, 23 cases had third, fourth, fifth and sixth line or more chemotherapy, respectively. Irinotecan-containing chemotherapy was done in 22 cases and 35 cased as second- + third-line therapy and fourth line or more, respectively. Gemcitabine-containing therapy was done in 35 cases with fourth line or more chemotherapy. The overall survival rate at median follow-up period was 95.7% in induction chemotherapy group (median follow-up; 53 months) and 69.2% in salvage chemotherapy group (median follow-up; 47 months). Clinical outcomes showed no evidence of disease (NED) was obtained in 91.5% and 90.3% with induction and second-line therapy, respectively. Noteworthy mentioned, about 40% patients had NED even in the fourth line or more chemotherapy group.


Very good and relatively good prognosis were obtained in the patients with induction and salvage chemotherapy at high volume center, respectively. Sequential continuous chemotherapy would be very important to manage ‘difficult-to-treat’ advanced germ cell tumors.

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