A phase I/II study of dose-intense paclitaxel with cisplatin and cyclophosphamide as initial therapy of poor-prognosis advanced-stage epithelial ovarian cancer.
Epithelial ovarian cancer patients with bulky residual tumor have a poor response to therapy and limited survival. We investigated the addition of dose-intense paclitaxel to cisplatin and cyclophosphamide for patients with FIGO III/IV epithelial ovarian cancer. Paclitaxel dose was intensified from 135 to 250 mg/m2 and administered in combination with cisplatin at > or = 75 mg/m2 and cyclophosphamide at 750 mg/m2. Thirty-one of 36 patients (86%) and 25 (70%) had > or = 2 and > or = 3 cm residual disease after surgery, respectively. One-third had stage IV disease, and 80% had grade 3 tumors. The maximally tolerated doses (MTD) were paclitaxel at 250 mg/m2, cisplatin at 75 mg/m2, and cyclophosphamide at 750 mg/m2 on a 21-day cycle with G-CSF, 10 micrograms/kg/day. Administered dose intensity at the MTD was > or = 86%. Reversible grade 3 peripheral neuropathy occurred in 28% of patients and fever during neutropenia in 2/352 cycles (0.5%). The pathologic response rate is 36% with an additional 25% having minimal microscopic disease. Median progression-free and overall survivals for patients receiving paclitaxel at 250 mg/m2 at a median potential follow-up of 22 months have not been reached for the cohort nor for the > or = 3-cm subgroup. This regimen should be evaluated in a prospective, randomized clinical trial.
Kohn
E C
EC
Medical Ovarian Cancer Section, Clinical Pharmacology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA.
Sarosy
G A
GA
Davis
P
P
Christian
M
M
Link
C E
CE
Ognibene
F P
FP
Sindelar
W F
WF
Jacob
J
J
Steinberg
S M
SM
Premkumar
A
A
Reed
E
E
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D003520:Cyclophosphamide; D017239:Paclitaxel; D002945:Cisplatin