Cisplatin and escalating doses of paclitaxel and epirubicin in advanced ovarian cancer. A phase I study.
OBJECTIVE
The combination of paclitaxel and cisplatin is considered the standard regimen for advanced ovarian cancer (AOC). A meta-analysis has shown that the incorporation of anthracyclines into first-line chemotherapy might improve long-term survival by 7-10%. We designed a phase I-II study in patients with AOC using a combination of a fixed dose of cisplatin with paclitaxel and epirubicin both given at escalating doses every 3 weeks. The objectives of this study were to determine both the maximum tolerated dose (MTD) and the antitumor activity of this combination.


METHODS
Six different dose levels were planned. The starting doses were cisplatin 75 mg/m2, paclitaxel 140 mg/m2, and epirubicin 50 mg/m2. The doses of paclitaxel were escalated in 20-mg/m2 increments, alternating with 20-mg/m2 increments of epirubicin. Ten patients with AOC entered the phase I study. Three patients each were enrolled at level I and level II and four patients at level III, and at each level, 15 courses were administered. Patients received a median of five courses.


RESULTS
Nonhematological toxicity was generally mild, except for grade 3 mucositis in one course at levels II and III, and grade 3 vomiting in one course at levels I and III. Hematological toxicities were grade 3-4 neutropenia in 60%, 47% and 60% of courses at levels I, II and III, respectively, and grade 3 anemia in one course at level III. At level III two of four patients developed a dose-limiting toxicity which was grade 4 neutropenia lasting more than 1 week.


CONCLUSIONS
The MTD was reached at level II with cisplatin 75 mg/m2, paclitaxel 160 mg/m2, and epirubicin 50 mg/m2. The phase II part of the study is currently ongoing.
Nardi
M
M
Department of Medical Oncology, Regina Elena National Cancer Institute, Rome, Italy. sdemarco@medscape.com
De Marco
S
S
Fabi
A
A
Aloe
A
A
Magnani
E
E
Pacetti
U
U
Carlini
P
P
Ruggeri
E M
EM
Cognetti
F
F
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
D015251:Epirubicin; D017239:Paclitaxel; D002945:Cisplatin