Multiple cycles of intermittent chemotherapy in metastatic androgen-independent prostate cancer

Abstract

Recently, completed phase III studies demonstrated a survival benefit for a fixed number of cycles of docetaxel-containing chemotherapy treatment of androgen-independent prostate cancer (AIPC). Management of patients who respond well to initial chemotherapy for AIPC remains ill-defined. We previously reported that in a select group of such patients, retreatment with the same regimen was feasible and was associated with quality of life gains. Here, we report that multiple cycles of such intermittent chemotherapy are feasible. We prospectively tested intermittent chemotherapy in eight AIPC patients responding to calcitriol plus docetaxel who reached a serum prostate-specific antigen (PSA) o4 ng ml À1 (22% of the 37 patients who were initially treated with this regimen). Chemotherapy was suspended until a rise in PSA X50% and 1 ng ml À1 . The median duration of the first treatment holiday was 20 weeks (13 -74 weeks) and all patients retained sensitivity to retreatment. Four patients were eligible for a second chemotherapy holiday, and the median duration was 21 weeks (17 -28 weeks). Two patients elected to take a third chemotherapy holiday, which lasted 10 and 28 weeks. The median time to treatment failure was 26.5 months (95% CI 23.6 -29.4 months), and the median survival is 41 months (95% CI 33.7 -48.3 months). Multiple cycles of intermittent chemotherapy interrupted by clinically meaningful treatment holidays are feasible in a subset of AIPC patients treated with this docetaxel-containing regimen. Intermittent chemotherapy for AIPC is feasible and deserves further study.

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

“…This finding suggests that disease control was comparable between the intermittent tri-weekly DTX with BCL schedule and the continuous regimen. However, the median OS was significantly shorter than that reported by Beer 20 (20 months vs. 41 months), who used intermittent weekly DTX plus high-dose calcitriol. This difference may have been due to different patient characteristics and different regimens; however, the median survival in our study was similar to a report by Soga,35 who used tri-weekly DTX plus estramustine (20 months vs. 21 months).…”

“…The first two trials reported median times of 4 and 4.5 months. 9,20 The third study reported a median time of 2.8 months. 21 We believe that the first DTX holiday in the three trials and the present study differed for the following reasons.…”

“…The amount of hormonal therapy is adversely related to the PSA response to DTX. 33 Only patients with prior flutamide treatment were enrolled in our study, whereas the patients in Beer's study 9,20 had received flutamide and BCL therapy. Finally, BCL might exert some activity against CRPC.…”

“…8,14,16 Patients with CRPC who previously had discontinued DTX treatment have recently been reported to be sensitive to DTX re-treatment. 17,18 Similarly, three single-arm trials have reported that the intermittent DTX approach displays comparable efficacy in patients with CRPC; [19][20][21] however, the three trials all used weekly DTX regimens rather than a tri-weekly regimen, which has a proven benefit with an OS increase of 2.5 months compared to controls. 5,6 Two important mechanisms underlying the development and progression of CRPC, which can be exploited therapeutically, are the overexpression of IL-6 and hypersensitivity or mutation of the androgen receptor, both of which contribute to CRPC.…”

Overcoming Chemotherapy Resistance in Prostate Cancer

“…Second, from a clinical perspective, breaks in therapy or "drug holidays" may improve the quality of life for patients, allowing them to recover from the cumulative toxicity of chemotherapy during these "drug holidays." Resolution of drug side effects may also allow taxane therapy to be prolonged, given evidence of clinical efficacy, which could also improve outcomes (31,32).…”