title: Phase I study of high-dose topotecan with haematopoietic stem cell support in the treatment of ovarian carcinomas: the ITOV 01 protocol.
abstract: 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 (MTD<12 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 toxicity >6 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.
authors.affiliation: Department of Medical Oncology, Hôpital Tenon, Assistance Publique - Hôpitaux de Paris, Université Pierre et Marie Curie, Paris, France. jean.pierre.lotz@tnn.ap-hop-paris.fr
authors.forename: J-P
authors.initials: JP
authors.lastname: Lotz
authors.forename: P
authors.initials: P
authors.lastname: Pautier
authors.forename: F
authors.initials: F
authors.lastname: Selle
authors.forename: P
authors.initials: P
authors.lastname: Viens
authors.forename: M
authors.initials: M
authors.lastname: Fabbro
authors.forename: F
authors.initials: F
authors.lastname: Lokiec
authors.forename: F
authors.initials: F
authors.lastname: Viret
authors.forename: J
authors.initials: J
authors.lastname: Gligorov
authors.forename: B
authors.initials: B
authors.lastname: Gosse
authors.forename: S
authors.initials: S
authors.lastname: Provent
authors.forename: V
authors.initials: V
authors.lastname: Ribrag
authors.forename: J-M
authors.initials: JM
authors.lastname: Micléa
authors.forename: C
authors.initials: C
authors.lastname: Dosquet
authors.forename: A
authors.initials: A
authors.lastname: Goetschel
authors.forename: C
authors.initials: C
authors.lastname: Cailliot
authors.forename: G
authors.initials: G
authors.lastname: Lefèvre
authors.forename: J
authors.initials: J
authors.lastname: Genève
authors.forename: C
authors.initials: C
authors.lastname: Lhommé
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D002277:Carcinoma / Q000188:drug therapy*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization / Q000009:adverse effects; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D015996:Survival Rate; D019772:Topotecan / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D019772:Topotecan