Phase I study of high-dose topotecan with haematopoietic stem cell support in the treatment of ovarian carcinomas: the ITOV 01 protocol
| Autor: | J.-M. Miclea, Patrice Viens, J. Geneve, S. Provent, Catherine Lhommé, F. Viret, Joseph Gligorov, G. Lefevre, Jean-Pierre Lotz, B. Gosse, Vincent Ribrag, C. Cailliot, A. Goetschel, François Lokiec, Frédéric Selle, C. Dosquet, Michel Fabbro, Patricia Pautier |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
medicine.medical_specialty Adolescent Maximum Tolerated Dose medicine.medical_treatment Antineoplastic Agents Neutropenia Gastroenterology Drug Administration Schedule Sepsis Pharmacokinetics Internal medicine medicine Mucositis Humans Aged Ovarian Neoplasms Transplantation Chemotherapy Dose-Response Relationship Drug business.industry Carcinoma Hematopoietic Stem Cell Transplantation Hematology Middle Aged medicine.disease Combined Modality Therapy Hematopoietic Stem Cell Mobilization Surgery Granulocyte colony-stimulating factor Survival Rate Regimen Treatment Outcome Female Topotecan business medicine.drug |
| Zdroj: | Bone Marrow Transplantation. 37:669-675 |
| ISSN: | 1476-5365 0268-3369 |
| Popis: | Topotecan has demonstrated activity in ovarian carcinomas. In order to increase the tumour response rate and to define the maximum tolerated dose (MTD) of topotecan, we decided to develop a high-dose phase I regimen supported by stem cell support. High-doses schedules using a 1-day single administration have MTDs of 10.5 (24 h continuous infusion (CI)) or 22.5 mg/m2 (30 min infusion). Five-day CI induces grade IV mucositis at high doses (MTD12 mg/m2). We chose to administer topotecan in a 5-day schedule with a 30 min daily infusion. Patients were scheduled to receive one cycle of therapy. The first dose level was 4.0 mg/m2/day x 5 days. Limiting toxicities were defined as toxic death, grade IV non-haematopoietic or haematopoietic toxicity6 weeks. From August 1998 to April 2002, 49 patients were included. Forty-three patients have completed one course and 15 have received two cycles. One patient treated at level 7 mg/m2/day died of sepsis. Median duration of grade IV neutropenia was 9 days. Two episodes of grade IV diarrhoea were observed at level 9.5 mg/m2/day. Pharmacokinetic data were linear within the dose range of 4-9.0 mg/m2/day. The MTD was reached at 9 mg/m2/day x 5 days. |
| Databáze: | OpenAIRE |
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