Article thumbnail

Dose and schedule-finding study of oral topotecan and weekly cisplatin in patients with recurrent ovarian cancer

By H Gelderblom, A Sparreboom, M J A de Jonge, W J Loos, E Wilms, M A Mantel, B Hennis, I Camlett, J Verweij and M E L van der Burg


Both weekly cisplatin chemotherapy and single agent topotecan have proven to be effective in recurrent ovarian cancer. Preclinical data show synergism between cisplatin and topotecan. Side effects for this combination are drug sequence dependent and predominantly haematologic. Since preclinical data suggest that Cremophor EL (CrEL), the formulation vehicle of paclitaxel, has a protective effect on haematological toxicity of cisplatin, CrEL was added to the combination cisplatin and topotecan. In this phase I study, escalating doses of oral topotecan administered on day 1, 2, 8, 9, 15, 16, 29, 30, 36, 37, 43, 44 were combined with weekly cisplatin 70 mg m−2d−1on day 1, 8, 15, 29, 36, 43 (scheme A) or with the presumably less myelotoxic sequence weekly cisplatin day 2, 9, 16, 30, 37, 44 (scheme B). In scheme C, CrEL 12 ml was administered prior to cisplatin in the sequence of Scheme A. 18 patients have received a total of 85 courses. In scheme A 4/10 patients, all treated with topotecan 0.45 mg m−2d−1, experienced DLT: 1 patient had vomiting grade 4, 1 patient had grade 4 neutropenia >5 days, 1 patient had >2 weeks delay due to thrombocytopenia and 1 patient due to neutropenia. Both patients in scheme B (topotecan 0.45 mg m−2d−1) had DLT due to a delay > 2 weeks because of prolonged haematological toxicity. No DLT was observed in the first 3 patients in scheme C (topotecan 0.45 mg m−2d−1). However, 2 out of 3 patients treated at dose level topotecan 0.60 mg m−2d−1in scheme C experienced DLT due to >2 weeks delay because of persistent thrombocytopenia or neutropenia. We conclude that there is a modest clinical effect of CrEL on haematological toxicity for this cisplatin-based combination regimen, which seems to reduce these side effects but does not really enable an increase of the oral topotecan dose. © 2001 Cancer Research Campaign

Topics: Regular Article
Publisher: Nature Publishing Group
OAI identifier:
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles


  1. (1997). Case report of anaphylaxis from cisplatin/paclitaxel and a review of their hypersensitivity reaction profiles.
  2. (2000). Differential alteration of cisplatin cytotoxicity and myelotoxicity by the vehicle Cremophor EL. Naunyn-Schmiedeberg Arch Pharmacol 361: 339–334
  3. (1994). Phase 1 study of topotecan and cisplatin in patients with advanced solid tumours: a cancer and leukemia group B study.
  4. (1994). Phase 1 trial of low continuous topotecan infusion in patients with cancer: An active and well tolerated regimen.