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Dose intense triplet chemotherapy with gemcitabine, carboplatin, paclitaxel with peripheral blood progenitor cell support for six cycles in advanced epithelial ovarian cancer

Authors
Journal
British Journal of Cancer
0007-0920
Publisher
Nature Publishing Group
Publication Date
Identifiers
DOI: 10.1038/sj.bjc.6601697
Keywords
  • Clinical
Disciplines
  • Medicine

Abstract

Dose intense triplet chemotherapy with gemcitabine, carboplatin, paclitaxel with peripheral blood progenitor cell support for six cycles in advanced epithelial ovarian cancer C Barlow1, M Nystrom1, C Oesterling1, D Fennell1, J Ismay1 and C Gallagher*,1 1Department of Medical Oncology, St Bartholomew’s Hospital, West Smithf ield, London EC1A 7BE, UK The interval required for haematological reconstitution following myelosuppressive chemotherapy can be reduced by the infusion of autologous peripheral blood progenitor cells (PBPCs). When carboplatin (C) and paclitaxel (P) are followed by granulocyte colony- stimulating factor (GCSF), multiple courses can be given at 10-day intervals with the autologous PBPCs from a unit of whole blood with each cycle. We extended this approach and defined the dose-limiting toxicity and maximum-tolerated dose for the addition of gemcitabine (G) to CP for patients (pts) with EOC in a phase I– II study of increasing doses of G (0, 800, 1000 and 1250 mg m�2) over four cohorts with C at area under curve (AUC) 6, plus P at 175 mg m�2 3 h�1 every 10 days for six cycles. Granulocyte colony- stimulating factor 5mg kg�1 day�1 was given s.c. days 1–10 and 450 ml whole blood was venesected before each treatment, stored untreated at 41C and reinfused 24 h later. In all, 17 patients with EOC either bulky stage IV or recurrent after treatment-free interval 412 months were treated over 30 months. Of the 17 patients, 13 completed six cycles (one patient stopped early with PD, three with toxicity), interdose interval 9–28 (median 10) days. Delays occurred in four patients due to infection or malaise, and there were no dose reductions. Haematological toxicity was not considered to be dose limiting. Febrile neutropenia was uncommon (2 patients), but grade III/IV thrombocytopenia was seen across all cohorts. Treatment was not delayed for thrombocytopenia and no bleeding complications occurred. Grade III transaminitis was seen in all patients in cohort 4 and grade IV toxicity, con

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