© 2004 Foundation for Promotion of Cancer Research
Cisplatin, Paclitaxel and Escalating Doses of Doxorubicin (TAP) in Advanced Ovarian Cancer: a Phase I Trial
1 Division of Gynecological Oncology and 2 Department of Medical Oncology, National Cancer Center Hospital, Tokyo, 3 Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Tokyo, 4 Department of Obstetrics and Gynecology, National Nagoya Hospital, Nagoya, 5 Department of Obstetrics and Gynecology, Sakai Hospital, Kinki University School of Medicine, Sakai, 6 Department of Obstetrics and Gynecology, National Kure Medical Center, Kure, Hiroshima, 7 Department of Obstetrics and Gynecology, Faculty of Medicine, Kyushu University, Fukuoka, 8 Department of Obstetrics and Gynecology, Kurume University School of Medicine, Kurume, Fukuoka, 9 Gynecology Service, National Kyushu Cancer Center, Fukuoka and 10 Department of Obstetrics and Gynecology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
For reprints and all correspondence: Takashi Onda, Division of Gynecological Oncology, National Cancer Center Hospital, 5–1–1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. E-mail: taonda{at}ncc.go.jp
Received April 3, 2004; accepted June 10, 2004
Background: The objectives of this phase I trial were to determine the maximum tolerated dose (MTD) and the recommended dose (RD) for phase II/III trials of doxorubicin (DOX) combined with paclitaxel (PTX) and cisplatin (CDDP) in patients with advanced ovarian cancer (AOC).
Methods: Twenty-eight patients with stage III/IV AOC received fixed doses of PTX (110 mg/m2 over 24 h on day 1) and CDDP (75 mg/m2 on day 2) and an escalating dose of DOX (20, 30, 40 or 50 mg/m2 on day 1) every 3 weeks. The patients received up to six cycles of chemotherapy. At level 1, one of the original dose-limiting toxicities (DLTs), grade (G) 4 neutropenia lasting for 4 days or longer, occurred in four of six patients. The criterion for DLT was amended to ‘G4 neutropenia lasting for 8 days or longer accompanied with G4 leukopenia’ and four additional patients were evaluated at level 1.
Results: According to the new criteria, DLT was observed only in one of nine patients except one ineligible patient at level 1and two of six patients at level 4. G4 neutropenia and G4 leukopenia occurred in 85% and 44%, respectively, in the first course of chemotherapy. Non-hematological toxicity was generally mild or moderate. MTD was not determined at the planned dose levels. A clinical response was observed in 16 of 19 (84%) evaluable patients. Further dose escalation was not performed and RD was determined as level 4 because more than 30% of cycles required some modification of chemotherapy at level 4.
Conclusion: The combination of TAP including 50 mg/m2 of DOX is feasible and well tolerated as first line chemotherapy in AOC, warranting further study of this regimen.
Key Words: ovarian cancer • chemotherapy • doxorubicin • phase I study