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Topotecan and carboplatin in patients with platinum-sensitive recurrent ovarian cancer. Results of a multicenter NOGGO: phase I/II study

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Abstract

Objective

Second-line treatment with paclitaxel and carboplatin enhances survival of women with platinum-sensitive recurrent ovarian cancer (ROC). However, because of its cumulative neurotoxicity, there is a strong demand for platinum-combinations with better therapeutic index. Because of its pharmacological properties, topotecan is a good adjunct to carboplatin in this setting, but its safety and efficacy remains to be defined.

Methods

Patients with platinum-sensitive ROC were eligible in this multicenter phase I/II study, stratified according to treatment-free interval (TFI). Dose level 0 consisted of topotecan 1 mg/m2/d1–3/q21d plus carboplatin AUC5/d3/q21d. DLT was defined as grade ≥3 neutropenia or thrombocytopenia or grade ≥3 non-hematological toxicity excluding alopecia, nausea and vomiting, accompanied by a treatment delay >1 week.

Results

From June 2004 to August 2005, 26 patients were enrolled, receiving a total of 145 cycles of chemotherapy. MTD was reached at topotecan 0.75 mg/m2 and carboplatin AUC5. We observed a single grade 4 leucopenia. There were 3 (12%), 15 (58%) and 8 (31%) events of grade 3/4 hematological anaemia, leucopenia, and thrombocytopenia. Response rate was 67% (95% CI 43–85), median progression-free survival 9.5 months (95% CI 7.3–12.0), median overall survival 19.4 months (95% CI 12.3–26.9). None of the toxicity or efficacy endpoints were associated with TFI.

Conclusion

Topotecan and carboplatin is a well tolerated novel doublet option for women with platinum sensitive ROC. We encourage further studies on this approach, but to limit the doses of topotecan to 0.75 mg/m2/d1–3 and carboplatin AUC 5/d3.

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Notes

  1. HECTOR; Hycamtin et carboplatin versus established regimens in the treatment of replapsed ovarian cancer.

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Acknowledgments

We would like to thank the nurses, study-coordinators and patients who participated in this trial.

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Authors and Affiliations

  1. Department of Obstetrics and Genecology, Charité University Hospital, Campus Virchow-Clinic, Berlin, Germany

    Dominique Koensgen, Peter Klare, Guelten Oskay-Oezcelik, Alexander Mustea, Alexandra Coumbos, Werner Lichtenegger & Jalid Sehouli

  2. Department of Trauma Surgery and Orthopaedics, Center for Clinical Research, Unfallkrankenhaus Berlin, Berlin, Germany

    Dirk Stengel

  3. Department of Gynaecology and Obstetrics, University Hospital of Greifswald, Greifswald, Germany

    Antje Belau

  4. Department of Gynaecology and Obstetrics, Klinikum Chemnitz, Chemnitz, Germany

    Thomas Steck

  5. Department of Gynaecology and Obstetrics, University Hospital of Jena, Jena, Germany

    Oumar Camara

  6. Department of Gynaecology and Obstetrics, Technical University of Munich, Munich, Germany

    Harald Sommer

  7. Department of Medical Affairs, GlaxoSmithkline Wellcome, Munich, Germany

    Thomas Bogenrieder

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  1. Dominique Koensgen
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on behalf of the NOGGO (North-Eastern German Society of Gynecological Oncology) Study Group Ovarian Cancer

Corresponding author

Correspondence to Jalid Sehouli.

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Koensgen, D., Stengel, D., Belau, A. et al. Topotecan and carboplatin in patients with platinum-sensitive recurrent ovarian cancer. Results of a multicenter NOGGO: phase I/II study. Cancer Chemother Pharmacol 62, 393–400 (2008). https://doi.org/10.1007/s00280-007-0617-2

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  • DOI: https://doi.org/10.1007/s00280-007-0617-2

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