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Solid Tumours

Phase II study of a multi-course high-dose chemotherapy regimen incorporating cyclophosphamide, thiotepa, and carboplatin in stage IV breast cancer

Bone Marrow Transplantation volume 28, pages 173–180 (2001)Cite this article

Abstract

The purpose of this study was to determine the feasibility and efficacy of multiple courses of high-dose cyclophosphamide, carboplatin and thiotepa with peripheral blood progenitor cell (PBPC) transplantation in women with advanced breast cancer. Forty-one patients with advanced hormone-refractory breast cancer were enrolled in the study. The treatment started with two courses of 5-fluorouracil 500 mg/m2, epirubicin 120 mg/m2 and cyclophosphamide 500 mg/m2 (FE120C) followed by PBPC harvesting. The high-dose regimen consisted of three subsequent courses of ‘tiny’ CTC, cyclophosphamide 4000 mg/m2, thiotepa 320 mg/m2 and carboplatin 1060 mg/m2 (target AUC 13.3 mg/ml/min) (tCTC) divided over 4 consecutive days. The second and third courses were scheduled to begin on day 28 after the previous transplantation. A total of 86 tCTC courses was given to 33 of the 41 enrolled patients. Major toxicities consisted of hemorrhagic cystitis (six patients), prolonged gastro-intestinal toxicity (three patients) and veno-occlusive disease (two patients). There was one therapy-related death (unknown cause). Twenty patients (49%) achieved a complete response, nine (22%) a partial response and three patients stable disease after treatment. The median follow-up of the surviving patients was 43 months (range 25–61). Six patients remain in complete remission beyond 3 years. At 4 years, the progression-free survival (PFS) and overall survival (OS) for the whole patient group were 23 and 30% with a median duration of 12 and 27 months, respectively and for FE120C-responsive patients 32 and 36%, respectively with a median duration of 15 and 33 months. In the patient group with a PFS ⩾ 18 months all patients had limited disease (metastatic disease in only one or two sites) and fewer patients had bone or liver metastases compared to the overall patient group (33% vs 51%). This report shows that three closely spaced courses of tCTC are feasible, with acceptable toxicity. Triple tCTC can achieve complete or partial remission in most patients and long-term PFS in a selected subgroup of patients who have limited metastatic disease and are responsive to conventional-dose chemotherapy. Bone Marrow Transplantation (2001) 28, 173–180.

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Acknowledgements

This study was supported in part by a grant from the Schumacher-Kramer Foundation and by NKI 97–1439 of the Dutch Cancer Society.

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Authors and Affiliations

  1. Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    JG Schrama, JW Baars, MJ Holtkamp, JH Schornagel & S Rodenhuis

  2. Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute and Slotervaart Hospital, Amsterdam, The Netherlands

    JH Beijnen

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Schrama, J., Baars, J., Holtkamp, M. et al. Phase II study of a multi-course high-dose chemotherapy regimen incorporating cyclophosphamide, thiotepa, and carboplatin in stage IV breast cancer. Bone Marrow Transplant 28, 173–180 (2001). https://doi.org/10.1038/sj.bmt.1703105

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