Phase 1 Study to Evaluate the Safety of Reducing the Prophylactic Dose of Dexamethasone around Docetaxel Infusion in Patients with Prostate and Breast Cancer

Abstract

Background: There is little evidence that supports the registered high dose of dexamethasone used around docetaxel. However, this high dose is associated with considerable side effects. This study evaluates the feasibility of reducing the prophylactic oral dosage of dexamethasone around docetaxel infusion. Patients and methods: Eligible patients had a histologically confirmed diagnosis of prostate or breast cancer and had received at least three cycles of docetaxel as monotherapy or combination therapy. Prophylactic dexamethasone around docetaxel infusion was administered in a de-escalating order per cohort of patients. Primary endpoint was the occurrence of grade III/IV fluid retention and hypersensitivity reactions (HSRs). Results: Of the 46 enrolled patients, 39 were evaluable (prostate cancer (n = 25), breast cancer (n = 14). In patients with prostate cancer, the dosage of dexamethasone was reduced to a single dose of 4 mg; in patients with breast cancer, the dosage was reduced to a 3-day schedule of 4 mg–8 mg–4 mg once daily, after which no further reduction has been tested. None of the 39 patients developed grade III/IV fluid retention or HSR. One patient (2.6%) had a grade 1 HSR, and there were six patients (15.4%) with grade I or II edema. There were no differences in quality of life (QoL) between cohorts. Conclusions: It seems that the prophylactic dose of dexamethasone around docetaxel infusion can be safely reduced with respect to the occurrence of grade III/IV HSRs or the fluid retention syndrome.

High dose of dexamethasone attenuates docetaxel-induced fluid retention in breast cancer treatment

“…However, docetaxel and DEX administration methods (particularly DEX initiation date and administration duration) in the present study were different from those of previous studies. Specifically, docetaxel dose for breast cancer treatment in a prospective phase I study (100 mg/m 2 ) was higher than ours although their incidence of all-grade DIFR was lower 10 . A previous study reported that Japanese patients are more susceptible to docetaxel-induced toxicities 13 .…”

“…To our knowledge, this is the first study to show that high-dose DEX prophylaxis attenuates DIFR. In contrast, previous reports suggested the possibility of reducing DEX dosage in docetaxel-containing treatment 10 – 12 . However, docetaxel and DEX administration methods (particularly DEX initiation date and administration duration) in the present study were different from those of previous studies.…”