Cisplatin, paclitaxel and escalating doses of doxorubicin (TAP) in advanced ovarian cancer: a phase I trial.
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/m(2) over 24 h on day 1) and CDDP (75 mg/m(2) on day 2) and an escalating dose of DOX (20, 30, 40 or 50 mg/m(2) 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 1 and 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.


CONCLUSIONS
The combination of TAP including 50 mg/m(2) of DOX is feasible and well tolerated as first line chemotherapy in AOC, warranting further study of this regimen.
Onda
Takashi
T
Division of Gynecological Oncology, National Cancer Center Hospital, 104-0045 Tokyo, Japan. taonda@ncc.go.jp
Katsumata
Noriyuki
N
Tsunematsu
Ryuichiro
R
Yasugi
Toshiharu
T
Mushika
Masafumi
M
Yamamoto
Kaichiro
K
Fujii
Tsuneo
T
Hirakawa
Toshio
T
Kamura
Toshiharu
T
Saito
Toshiaki
T
Yoshikawa
Hiroyuki
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D014840:Vomiting, Anticipatory / Q000209:etiology
D004317:Doxorubicin; D017239:Paclitaxel; D002945:Cisplatin