Pa. Vasey et al., Docetaxel and cisplatin in combination as first-line chemotherapy for advanced epithelial ovarian cancer, J CL ONCOL, 17(7), 1999, pp. 2069-2080
Purpose: A prospective, nonrandomized, multicenter, open feasibility study
of cisplatin and docetaxel as first-line chemotherapy in International Fede
ration of Gynecology and Obstetrics (FIGO) stage IC-IV epithelial ovarian c
ancer was conducted. The primary end point was the incidence of severe flui
d retention that necessitated treatment withdrawal.
Patients and Methods: Cisplatin and docetaxel were administered every 3 wee
ks for six planned cycles, with a 5-day prophylactic dexamethasone regimen
(8 mg two times per day). One hundred patients (median age, 53 years; range
, 24 to 71 years) received a total of 512 cycles of chemotherapy in two coh
orts: cohort 1, 49 patients, 258 cycles (cisplatin 75 mg/m(2) and docetaxel
75 mg/m(2)); cohort 2, 51 patients, 254 cycles (cisplatin 75 mg/m(2) and d
ocetaxel 85 mg/m2).
Results: No patients were taken off study because of fluid retention. Sixty
-six patients completed six cycles of protocol therapy; 16 stopped early be
cause of toxicity (neurotoxicity in six patients, nephrotoxicity in three,
neutropenia in two, and hypersensitivity, diarrhea and vomiting, skin rash,
clinical deterioration, and patient's wishes in one patient each). Grade 3
/4 neutropenia was observed in more than 75% of patients and seemed to be c
umulative. Patients in cohort 2 had significantly more severe neutropenia a
nd lethargy than those in cohort 1. In addition, there were five treatment-
related deaths in cohort 2 (three neutropenia and two upper gastrointestina
l hemorrhage), Neurotoxicity (mainly sensory, > grade 1) was observed in 23
patients. The overall clinical response rate was 69% (complete response, 3
8%; partial response, 31%); CA-125 response rate was 73%. Median progressio
n-free survival for the group was 12 months.
Conclusion: Cisplatin and docetaxel can be administered at doses of 75 mg/m
(2) and 75 mg/m(2), respectively, every 3 weeks, and the utility of this re
gimen is not limited by fluid retention. However, 33 of 100 patients were u
nable to complete the planned six cycles, which may explain, in part, the p
oor overall progression-free survival. increasing the docetaxel dose to 85
mg/m2 adds unacceptable hematologic toxicity and potential risks to the pat
ient. (C) 1999 by American Society of Clinical Oncology.