Intermittent tri-weekly docetaxel plus bicalutamide in patients with castration-resistant prostate cancer: a single-arm prospective study using a historical control for comparison

Abstract

Whether continuous docetaxel (DTX) chemotherapy offers an advantage over intermittent therapy for castration-resistant prostate cancer (CRPC) is unknown. In this study, we evaluated the efficacy, toxicity and quality of life (QoL) of intermittent tri-weekly DTX with bicalutamide in CRPC. Forty-two patients (group A) with CRPC were enrolled. The patients received intravenous DTX (75 mg m 22 ) once tri-weekly with oral bicalutamide (50 mg) once daily. Patients had a DTX holiday when the prostate-specific antigen (PSA) level declined o50%. DTX was restarted in patients with a PSA increase o25%. Sixty patients (group B) who had matching characteristics and had continuously received DTX without bicalutamide for 10-12 cycles were also enrolled. There were no statistically significant differences in progression-free survival (8 months vs. 9 months, P50.866) or overall survival (19 months vs. 21 months, P50.753) between groups A and B; however, the proportions of patients in group A with all grades of neutropenia (33% vs. 58%, P50.013) and nausea/vomiting (11% vs. 29%, P50.024) were significantly less compared to group B. A significant improvement in the global health and fatigue scores was recorded for group A post-chemotherapy compared to pre-chemotherapy (P,0.05). The fatigue, nausea/ vomiting and appetite loss scores in group B were increased post-chemotherapy compared to pre-chemotherapy (P,0.05). In conclusion, intermittent tri-weekly DTX plus bicalutamide is well tolerated and has the potential to achieve comparable disease control with an improvement in QoL for patients with CRPC.

Intermittent vs continuous docetaxel therapy in patients with metastatic castration‐resistant prostate cancer – a phase III study (PRINCE)

“…This is comparable to the median duration of the first treatment holidays found in other studies: 18 weeks (range 4–70) for patients in the Androgen‐independent prostate cancer Study of Calcitriol ENhancing Taxotere (ASCENT) trial who received intermittent docetaxel plus either calcitriol or placebo (45/250 patients) and 5.3 months (range 2–20) reported by Li et al. , which dropped to 2.8 months (range 1–7) in the second holiday; 67% of patients (28/42) with intermittent treatment reached the first docetaxel holiday and the therapy was well tolerated.…”

“…Data on intermittent vs continuous docetaxel treatment is limited. The efficacy of an intermittent docetaxel therapy or docetaxel rechallenge has been tested in a few retrospective studies and in one prospective one-armed study with a historical control group [25][26][27][28]. These studies observed median OS of 15.8-19 months for intermittent docetaxel, corresponding well to the OS seen in the present study, with one exception where a median OS of 13 months was stated [25], probably due to higher age of enrolled patients [26][27][28].…”

“…QoL was not assessed in the present study, but based on the results reported by Li et al. it can be hypothesised that intermittent docetaxel therapy improves QoL at least for some parameters. Patients receiving intermittent docetaxel had a median (range) treatment holiday of 110 (13–486) days, comprising 38% of the overall treatment duration.…”

“…In a prospective study by Li et al. there was no significant difference in PFS (8 vs 9 months) and OS (19 vs 21 months) between the group treated with intermittent 3‐weekly docetaxel plus bicalutamide and a historical continuous docetaxel plus bicalutamide control group.…”

Targeting MRP4 expression by anti-androgen treatment reverses MRP4-mediated docetaxel resistance in castration-resistant prostate cancer

“…In addition, it was reported that MRP4 expression levels increased with androgen treatment, but decreased with anti-androgen treatment, in LNCaP cells (25). Furthermore, our previous study demonstrated that DTX-resistance time in patients with low testosterone levels was significantly delayed compared with that in patients with high testosterone levels (26). These data indicated that androgen levels may be associated with DTX resistance.…”