Topotecan and carboplatin in patients with platinum-sensitive recurrent ovarian cancer. Results of a multicenter NOGGO: phase I/II study
| Autor: | Thomas Steck, Alexandra Coumbos, Guelten Oskay-Oezcelik, Harald Sommer, Alexander Mustea, Dominique Koensgen, Oumar Camara, Jalid Sehouli, Thomas Bogenrieder, Peter Klare, Werner Lichtenegger, Dirk Stengel, Antje Belau |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Oncology Cancer Research medicine.medical_specialty endocrine system diseases medicine.medical_treatment Toxicology Disease-Free Survival Carboplatin chemistry.chemical_compound Therapeutic index Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Pharmacology (medical) Prospective Studies Prospective cohort study Aged Ovarian Neoplasms Pharmacology Chemotherapy business.industry Cancer Middle Aged medicine.disease female genital diseases and pregnancy complications Surgery Clinical trial chemistry Paclitaxel Drug Resistance Neoplasm Female Topotecan Neoplasm Recurrence Local business medicine.drug |
| Zdroj: | Cancer Chemotherapy and Pharmacology. 62:393-400 |
| ISSN: | 1432-0843 0344-5704 |
| Popis: | 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.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/m(2)/d1-3/q21d plus carboplatin AUC5/d3/q21d. DLT was defined as gradeor =3 neutropenia or thrombocytopenia or gradeor =3 non-hematological toxicity excluding alopecia, nausea and vomiting, accompanied by a treatment delay1 week.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/m(2) 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.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/m(2)/d1-3 and carboplatin AUC 5/d3. |
| Databáze: | OpenAIRE |
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