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Phase 1/pharmacology study of intraperitoneal topotecan alone and with cisplatin: potential for consolidation in ovarian cancer

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Abstract

Purpose

Most ovarian cancers recur after first-line treatment. We studied the pharmacology, tolerability, and therapeutic potential of intraperitoneal (IP) topotecan, alone and with IP cisplatin.

Methods

Patients received IP topotecan 1.5 mg (flat dose) daily on days 1–5 (level 0) via IP catheter. Subsequent cohorts received IP cisplatin 50 mg/m2 on day 1 added to topotecan 1.5 mg on days 1–3 (level I), topotecan 1.25 mg on days 1–3 (level II), or topotecan 1.25 mg on days 1–5 (level III). Plasma and IP concentrations of total and lactone (E-ring closed) topotecan were measured on days 1 and 2 in cycles 1 and 2.

Results

Sixteen patients (15 tubo-ovarian, 1 gastric cancers) were entered at levels 0 (3), I (4), II (4), or III (5). Dose-limiting neutropenias occurred in seven patients at dose levels I and III; grade 3 thrombocytopenia occurred in two at level III. Other toxicities included grade 1 hives in two, serum creatinine elevations in two, and Staphylococcus epidermidis and chemical peritonitis (one each). A median progression-free survival of 13 months was recorded among ovarian cancer patients who had minimal (6) or no residuum (3) after platinum-based induction; 5 are alive at 4 years. Topotecan’s AUC IP/AUC plasma ratios ranged from 13 to 119.

Conclusion

Topotecan IP for 3–5 days is tolerable; occasionally, myelosuppression is dose-limiting. Topotecan 1.25 mg (days 1–3) with IP cisplatin 50 mg/m2 (day 1) is a regimen suitable for consolidation in phase 3 trials.

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Acknowledgments

Supported in part by grants from Glaxo Smith-Kline, The Chemotherapy Foundation, and the GCRC M01 RR00096.

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Authors and Affiliations

  1. Department of Medical Oncology, Breast Section, Montefiore Medical Center/Albert Einstein Cancer Center, 1825 Eastchester Road, Rm. 2555, Bronx, NY, 10461, USA

    Eleni Andreopoulou

  2. Banner Health, Sun City West Clinic, 14416 West Meeker Boulevard, Sun City West, AZ, 85375, USA

    Thomas Chen

  3. NYU Cancer Institute, 550 First Avenue, BCD556, New York, NY, 10016, USA

    Leonard Liebes, John Curtin, Stephanie Blank, Robert Wallach & Franco Muggia

  4. Yale Cancer Center, PO Box 208028, New Haven, CT, 06520-8028, USA

    Howard Hochster

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  1. Eleni Andreopoulou
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  2. Thomas Chen
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  3. Leonard Liebes
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  8. Franco Muggia
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Correspondence to Franco Muggia.

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Andreopoulou, E., Chen, T., Liebes, L. et al. Phase 1/pharmacology study of intraperitoneal topotecan alone and with cisplatin: potential for consolidation in ovarian cancer. Cancer Chemother Pharmacol 68, 457–463 (2011). https://doi.org/10.1007/s00280-010-1510-y

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  • DOI: https://doi.org/10.1007/s00280-010-1510-y

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