CORTICOSTEROIDS SIGNIFICANTLY DELAY THE ONSET OF DOCETAXEL-INDUCED FLUID RETENTION - FINAL RESULTS OF A RANDOMIZED STUDY OF THE -ORGANIZATION-FOR-RESEARCH-AND-TREATMENT-OF-CANCER INVESTIGATIONAL DRUG BRANCH FOR BREAST-CANCER

Purpose: To confirm the efficacy of docetaxel in patients with breast cancer previously treated with one chemotherapy regimen for advanced o r metastatic disease and to compare the incidence of fluid retention ( FR) and skin toxicity when docetaxel is administered with and without prophylactic corticosteroids. Patients and Methods: Eighty-three patie nts, pretreated with one chemotherapy regimen for metastatic breast ca ncer (MBC) with bidimensionally measurable and progressive disease, we re eligible for this randomized trial. Docetaxel with prophylactic ora l antihistamine was administered at a dose of 50 mg/m(2) as a 1-hour i nfusion on days 1 and 8 every 21 days and patients were randomized to receive methylprednisolone (40 mg days -1, 0, 1, 7, 8, and 9 of each c ycle) (arm A) or no methylprednisolone (arm B). Results: Twenty-eight patients (34%; 95% confidence interval [CI], 23% to 45%) achieved an o bjective response. The median time to disease progression and median o verall survival time were 5 and 13.5 months, respectively. In total, 4 15 cycles of docetaxel were administered (arm A: N = 219, median = six ; arm B: N = 196, median = five), The most common toxicity observed wa s grade 3 or 4 neutropenia, which occurred in 79% of patients. Clinica lly significant nonhematologic side effects included skin reactions an d asthenia. In an intent-to-treat analysis, patients who received meth ylprednisolone premedication had a delayed onset of FR (median time to onset of FR: arm A, 84 days; arm B, 62 days; P = .01) and received a higher median cumulative dose of docetaxel before the onset of FR (arm A, 333 mg/m(2); arm B, 215 mg/m(2); P = .001). There was no statistic ally significant difference in the incidence of skin toxicity between the two arms. Conclusion: Docetaxel, at this dose and schedule, has de finite antitumor activity in pretreated MBC patients. Moreover, this i s the first randomized trial to show that corticosteroids have a favor able impact on docetaxel-induced FR. (C) 1997 by American Society of C linical Oncology.