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Autografting

Phase I trial of autologous hematopoietic SCT with escalating doses of topotecan combined with CY and carboplatin in patients with relapsed or persistent ovarian or primary peritoneal carcinoma

Bone Marrow Transplantation volume 45, pages 490–497 (2010)Cite this article

Abstract

We designed a phase I clinical trial of escalating doses of topotecan with CY and carboplatin in combination with autologous hematopoietic SCT (AHSCT) for the treatment of relapsed or persistent platinum sensitive ovarian or primary peritoneal carcinoma. After stem cell collection, 16 patients received topotecan at 1.5, 2.5, 3.5, 4.5 or 6.0 mg/m2/d combined with CY 1.5 g/m2/d and carboplatin 200 mg/m2/d, all by 4-day continuous infusion. Steady state pharmacokinetics of topotecan and carboplatin were examined. Pre-treatment biopsies were examined for the expression of topoisomerase (topo) I, Ki67 and Bcl-2 family members by immunohistochemistry. One of six patients at a topotecan dose of 4.5 mg/m2/d and two of three patients at 6.0 mg/m2/d had dose-limiting toxicity of grade 3 stomatitis lasting >2 weeks. There was no treatment-related mortality. As topotecan clearance was constant over the dose range examined, topotecan steady state plasma concentrations increased with dose. Median progression-free survival and overall survival were 6.5 months and 2.7 years, respectively. Shorter progression-free survival was observed in tumors with low topo expression (P=0.04). Topotecan can safely be dose escalated to 4.5 mg/m2/d in combination with CY, carboplatin and AHSCT. This trial is registered at ClinicalTrials.gov as NCT00652691.

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Acknowledgements

We thank the Mayo Clinic Tissue and Cell Molecular Analysis Shared Resources for assistance with the immunohistochemical analyses of biopsy samples and gratefully acknowledge the contributions of Margo Marzolf for data support, Kim Kalli for sample acquisition and Denise Chase for manuscript preparation. M. Litzow received research funding support from GlaxoSmithKline to conduct this research: Glaxo SmithKline, R01 CA73709, P30 CA15083.

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Authors and Affiliations

  1. Division of Hematology, Mayo Clinic Cancer Center, Mayo Clinic College of Medicine, Rochester, MN, USA

    M R Litzow, S M Ansell, A Dispenzieri, M A Elliott, D A Gastineau, M A Gertz, D J Inwards, M Q Lacy, I N M Micallef, L F Porrata & S H Kaufmann

  2. Division of Medical Oncology, Mayo Clinic Cancer Center, Mayo Clinic College of Medicine, Rochester, MN, USA

    P P Peethambaram, L C Hartmann, M H Frost, B A Barrette & H J Long

  3. Division of Oncology Research, Mayo Clinic Cancer Center, Mayo Clinic College of Medicine, Rochester, MN, USA

    S L Safgren, J M Reid, M M Ames & S H Kaufmann

  4. Department of Laboratory Medicine and Pathology, Mayo Clinic Cancer Center, Mayo Clinic College of Medicine, Rochester, MN, USA

    G L Keeney & W L Lingle

  5. Cancer Statistics, Mayo Clinic Cancer Center, Mayo Clinic College of Medicine, Rochester, MN, USA

    V J Suman

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Correspondence to M R Litzow.

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Litzow, M., Peethambaram, P., Safgren, S. et al. Phase I trial of autologous hematopoietic SCT with escalating doses of topotecan combined with CY and carboplatin in patients with relapsed or persistent ovarian or primary peritoneal carcinoma. Bone Marrow Transplant 45, 490–497 (2010). https://doi.org/10.1038/bmt.2009.181

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  • DOI: https://doi.org/10.1038/bmt.2009.181

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