A phase II study using a topoisomerase I-based approach in patients with multiply relapsed germ-cell tumours

• Published in: Annals of oncology Vol. 18; no. 5; pp. 925 - 930
• Main Authors: Shamash, J, Powles, T, Mutsvangwa, K, Wilson, P, Ansell, W, Walsh, E, Berney, D, Stebbing, J, Oliver, T
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.05.2007; Oxford Publishing Limited (England)
• Subjects: Adolescent; Adult; Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Camptothecin - administration & dosage; Camptothecin - adverse effects; Camptothecin - analogs & derivatives; Follow-Up Studies; germ-cell tumour; Humans; Irinotecan; Male; mediastinal; Mediastinal Neoplasms - drug therapy; Mediastinal Neoplasms - pathology; Medical sciences; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - pathology; Neoplasms, Germ Cell and Embryonal - drug therapy; Neoplasms, Germ Cell and Embryonal - pathology; Organoplatinum Compounds - administration & dosage; Organoplatinum Compounds - adverse effects; Oxaliplatin; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; Pharmacology. Drug treatments; phase 2; relapsed; Survival Analysis; Testicular Neoplasms - drug therapy; Testicular Neoplasms - pathology; Time Factors; Topoisomerase I Inhibitors; Treatment Outcome; relapsed; phase 2; mediastinal; germ-cell tumour; Human; Relapse; Enzyme; Mediastinum; DNA topoisomerase; Germ cell tumor; Isomerases; Treatment; Phase II trial
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdm002

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.