BACKGROUND: The outcome of patients with germ-cell tumours (GCTs), who relapse more than once or relapse with a mediastinal primary is poor. We have shown that topoisomerase 1 may be an attractive target in relapsed GCT. We investigated the role of irinotecan, paclitaxel and oxaliplatin (IPO) followed by topotecan-based high-dose therapy in responding patients, in this patient population. PATIENTS AND METHODS: Twenty-eight patients with multiply relapsed gonadal and mediastinal GCT were recruited to this phase 2 study. All patients received IPO chemotherapy and 12 (43%) went on to receive high-dose therapy. The outcome of these patients was assessed using the Kaplan-Meier method with a median progression-free follow-up of 1 year. RESULTS: Twenty patients (71%) responded to the therapy including five complete remissions (18%), 13 (46%) marker-negative partial responses and two (7%) marker-positive partial responses. Nine (32%) patients continue to be progression free, and the median survival for the whole group currently measures 17 months. Out of 12 individuals who received subsequent high-dose therapy consolidation, seven (58%) remain progression free. The commonest grade III/IV toxicity was infection (68%) and there were no IPO-related toxic deaths; there was one death from high-dose therapy. CONCLUSION: Topoisomerase I-based IPO chemotherapy that lacks etoposide is very active in multiply relapsed GCT. This data merit further investigation.
BACKGROUND: The outcome of patients with germ-cell tumours (GCTs), who relapse more than once or relapse with a mediastinal primary is poor. We have shown that topoisomerase 1 may be an attractive target in relapsed GCT. We investigated the role of irinotecan, paclitaxel and oxaliplatin (IPO) followed by topotecan-based high-dose therapy in responding patients, in this patient population. PATIENTS AND METHODS: Twenty-eight patients with multiply relapsed gonadal and mediastinal GCT were recruited to this phase 2 study. All patients received IPO chemotherapy and 12 (43%) went on to receive high-dose therapy. The outcome of these patients was assessed using the Kaplan-Meier method with a median progression-free follow-up of 1 year. RESULTS: Twenty patients (71%) responded to the therapy including five complete remissions (18%), 13 (46%) marker-negative partial responses and two (7%) marker-positive partial responses. Nine (32%) patients continue to be progression free, and the median survival for the whole group currently measures 17 months. Out of 12 individuals who received subsequent high-dose therapy consolidation, seven (58%) remain progression free. The commonest grade III/IV toxicity was infection (68%) and there were no IPO-related toxic deaths; there was one death from high-dose therapy. CONCLUSION: Topoisomerase I-based IPO chemotherapy that lacks etoposide is very active in multiply relapsed GCT. This data merit further investigation.
Authors: Y Rimmer; J Chester; J Joffe; D Stark; J Shamash; T Powles; J White; J Wason; D Parashar; G Armstrong; D Mazhar; M V Williams Journal: Br J Cancer Date: 2011-08-16 Impact factor: 7.640
Authors: Damon R Reed; Leo Mascarenhas; Kathleen Manning; Gregory A Hale; John Goldberg; Jonathan Gill; Eric Sandler; Michael S Isakoff; Tiffany Smith; Jamie Caracciolo; Richard M Lush; Tzu-Hua Juan; Jae K Lee; Anthony M Neuger; Daniel M Sullivan Journal: Cancer Med Date: 2015-12-29 Impact factor: 4.452
Authors: Christopher L Cubitt; Jiliana Menth; Jana Dawson; Gary V Martinez; Parastou Foroutan; David L Morse; Marilyn M Bui; G Douglas Letson; Daniel M Sullivan; Damon R Reed Journal: Sarcoma Date: 2013-10-24