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Autografting

Phase I study of high-dose topotecan with haematopoietic stem cell support in the treatment of ovarian carcinomas: the ITOV 01 protocol

Bone Marrow Transplantation volume 37, pages 669–675 (2006)Cite this article

Abstract

Topotecan has demonstrated activity in ovarian carcinomas. In order to increase the tumour response rate and to define the maximum tolerated dose (MTD) of topotecan, we decided to develop a high-dose phase I regimen supported by stem cell support. High-doses schedules using a 1-day single administration have MTDs of 10.5 (24 h continuous infusion (CI)) or 22.5 mg/m2 (30 min infusion). Five-day CI induces grade IV mucositis at high doses (MTD<12 mg/m2). We chose to administer topotecan in a 5-day schedule with a 30 min daily infusion. Patients were scheduled to receive one cycle of therapy. The first dose level was 4.0 mg/m2/day × 5 days. Limiting toxicities were defined as toxic death, grade IV non-haematopoietic or haematopoietic toxicity >6 weeks. From August 1998 to April 2002, 49 patients were included. Forty-three patients have completed one course and 15 have received two cycles. One patient treated at level 7 mg/m2/day died of sepsis. Median duration of grade IV neutropenia was 9 days. Two episodes of grade IV diarrhoea were observed at level 9.5 mg/m2/day. Pharmacokinetic data were linear within the dose range of 4–9.0 mg/m2/day. The MTD was reached at 9 mg/m2/day × 5 days.

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Acknowledgements

We thank all the research nurses of the Bone Marrow Transplant Units for their expert and compassionate care of our patients, the secretaries for their help in the realization of this study, Graham A Ross for his editorial assistance and GlaxoSmithKline and Amgen Laboratories.

Author information

Author notes

  1. J-P Lotz, P Pautier, F Selle, P Viens, M Fabbro, F Lokiec, F Viret, J Gligorov, B Gosse, S Provent, V Ribrag, J-M Micléa, C Dosquet, A Goetschel, C Cailliot, G Lefèvre, J Genève and C Lhommé: Fédération Nationale des Centres de Lutte Contre le Cancer, 101 rue de Tolbiac, Paris, France.

Authors and Affiliations

  1. Department of Medical Oncology, Hôpital Tenon, Assistance Publique – Hôpitaux de Paris, Université Pierre et Marie Curie, Paris, France

    J-P Lotz, F Selle, J Gligorov, S Provent & G Lefèvre

  2. Department of Medical Oncology, Institut Gustave-Roussy, Villejuif, France

    P Pautier, V Ribrag & C Lhommé

  3. Department of Medical Oncology, Institut Paoli-Calmette, Marseille, France

    P Viens & F Viret

  4. Department of Medical Oncology, Centre Val d'Aurelle, Montpellier, France

    M Fabbro

  5. Department of Pharmacology, Centre René Huguenin, St-Cloud, France

    F Lokiec

  6. Department of Pharmacology, Le Cannet, France

    B Gosse

  7. Department of Haematology and Apheresis Units, Hôpital St-Louis, Paris, France

    J-M Micléa & C Dosquet

  8. Laboratories Glaxo-SmithKline, Marly Le Roi, France

    A Goetschel

  9. Laboratoires Amgen, Neuilly sur Seine, France

    C Cailliot

  10. Fédération Nationale des Centres de Lutte Contre Le Cancer, Paris, France

    J Genève

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  1. J-P Lotz
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on behalf of the Groupe d'Intensification des traitements des Tumeurs Ovariennes (ITOV Group)

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Correspondence to J-P Lotz.

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Lotz, JP., Pautier, P., Selle, F. et al. Phase I study of high-dose topotecan with haematopoietic stem cell support in the treatment of ovarian carcinomas: the ITOV 01 protocol. Bone Marrow Transplant 37, 669–675 (2006). https://doi.org/10.1038/sj.bmt.1705310

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