Docetaxel rechallenge after an initial good response in patients with metastatic castration‐resistant prostate cancer

Abstract

ObjectiveTo evaluate the benefit of docetaxel rechallenge in patients with metastatic castration-resistant prostate cancer (mCRPC) relapsing after an initial good response to first-line docetaxel. Patients and MethodsWe retrospectively reviewed the records of consecutive patients with mCRPC with a good response to first-line docetaxel [serum prostate specific antigen (PSA) decrease ≥50%; no clinical/radiological progression]. We analysed the impact of management at relapse (docetaxel rechallenge or non-taxane-based therapy) on PSA response, symptomatic response (performance status/pain/analgesic consumption), and overall survival (OS). We used multivariate stepwise logistic regression to analyse potential predictors of a favourable outcome. ResultsWe identified 270 good responders to first-line docetaxel. The median progression-free interval (PFI) was 6 months from the last docetaxel dose. At relapse, 223 patients were rechallenged with docetaxel (82.5%) and 47 received non-taxane-based therapy. There was no significant difference in median OS {18.2 [95% confidence interval (CI) 16.1-22.00] and 16.8 [95%CI 13.4-21.5] months, respectively, P = 0.35}. However, good PSA response and symptom relief/stable disease were more frequent on docetaxel rechallenge (40.4% vs 10.6%, P < 0.001 for PSA). A PFI of >6 months and added estramustine predicted a good PSA response and symptomatic response on docetaxel rechallenge but only a PFI of >6 months predicted longer OS. Haemoglobin (<13 g/dL) and pain were associated with reduced OS. Docetaxel rechallenge increased the incidence of grade ≥3 sensory neuropathy, nail disorders and asthenia/fatigue. ConclusionsDocetaxel rechallenge is a management option for responders to docetaxel with a PFI of >6 months, but did not prolong survival. Potential benefits should be weighed against the risk of cumulative toxicity.

Systemic Medical Treatment in Men with Metastatic Castration-Resistant Prostate Cancer: Recommendations for Daily Routine

“…Similar data have been described by Oudard et al [47] in a retrospective study analyzing 223 and 47 mCRPC patients with good response to first-line docetaxel who were exposed to a docetaxel rechallenge or who received non-taxane-based chemotherapy. Although there was a statistically significant difference in terms of PSA response and symptom relief (40.4 vs. 10.6%; p = 0.001) for the docetaxel arm, OS was not prolonged (18.2 vs. 16.8 months; p = 0.35) between the 2 groups.…”

“…This approach has never been tested in prospective randomized clinical trials, but there is level II-III evidence from retrospective series to identify patients who might be good candidates for re-exposure to docetaxel [46,47,48,49,50,51] (table 3). Patients who respond with a PSA decrease ≥ 30% maintained for at least 8 weeks after the end of docetaxel treatment demonstrate a positive PSA response in about 55-60% during re-exposure without increasing treatment-related toxicity.…”

“…It has to be mentioned that even in the presence of these risk factors, prophylactic application of G-CSF significantly reduced the risk of neutropenic complications by 30% (odds ratio (OR) 0.70, 95% CI 0.50-0.99, p = 0.04). In another study by the French group, Oudard et al [47] demonstrated that CBZ/P is equally effective in poorly differentiated prostate cancer with a Gleason score of 8-10 resulting in a survival benefit of 2.5 months over mitoxantrone/prednisone (15.2 vs. 12.7 months; p < 0.001). …”

Treatment sequence in castration-resistant prostate cancer: A retrospective study in the new anti-androgen era

“…However, it must be considered that the reintroduction of DOC may reduce the possibility that one of the novel treatment options available could then be administered. Furthermore, the situation is complicated by recent clinical trials that may lead to the early administration of DOC in combination with androgen-deprivation therapy, or to novel indications of AA and EZL in pre-DOC patients (13,14). In this setting, certain prior reports have indicated the possibility of the occurrence of cross-resistance when first-line chemotherapy with DOC was administered after the novel hormonal agent AA; by contrast, there have been few instances of DOC rechallenge following failure to respond to AA or other agents (15,16).…”

Comparison of Abiraterone Acetate and Docetaxel with Androgen Deprivation Therapy in High-risk and Metastatic Hormone-naïve Prostate Cancer: A Systematic Review and Network Meta-analysis

“…Oudard и соавт. по результатам ретроспективного анализа лечения 223 пациентов с прогрессированием при терапии доцетакселом сделали вывод о возможной эффективности его повторного назначения при про-должительном первичном ответе (более 18 мес) [58].…”