Cancer Chemotherapy and Pharmacology

, Volume 68, Issue 2, pp 457–463

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

  • Eleni Andreopoulou
  • Thomas Chen
  • Leonard Liebes
  • John Curtin
  • Stephanie Blank
  • Robert Wallach
  • Howard Hochster
  • Franco Muggia
Original Article

DOI: 10.1007/s00280-010-1510-y

Cite this article as:
Andreopoulou, E., Chen, T., Liebes, L. et al. Cancer Chemother Pharmacol (2011) 68: 457. doi:10.1007/s00280-010-1510-y

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.

Keywords

Intraperitoneal Ovarian cancer Topotecan Cisplatin 

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Eleni Andreopoulou
    • 1
  • Thomas Chen
    • 2
  • Leonard Liebes
    • 3
  • John Curtin
    • 3
  • Stephanie Blank
    • 3
  • Robert Wallach
    • 3
  • Howard Hochster
    • 4
  • Franco Muggia
    • 3
  1. 1.Department of Medical Oncology, Breast SectionMontefiore Medical Center/Albert Einstein Cancer CenterBronxUSA
  2. 2.Banner Health, Sun City West ClinicSun City WestUSA
  3. 3.NYU Cancer InstituteNew YorkUSA
  4. 4.Yale Cancer CenterNew HavenUSA

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