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.
Pesticide exposure assessment is a key methodological issue for epidemiological studies. The history of pesticide has proven difficult to obtain from individuals' report because of the wide range of active ingredients (AIs). We developed a crop-exposure matrix, which intends to reconstitute parameters of pesticide exposure in France since 1950. PESTIMAT is composed of tables crossing crops and AIs by year and providing the following metrics: (1) probability (proportion of farmers having used the AIs); (2) frequency (number of treatment days); and (3) intensity (application rate of the AIs in kg/ha). Metrics were obtained by the combination of six sources: (i) registration information from the Agriculture Ministry; (ii) information from agricultural bodies on products marketed; (iii) agricultural recommendations by the Plant Health Protection body; (iv) treatment calendars provided by farmers; (v) data from associations of farmers; and (vi) data from the industry. To date, 529 AIs usable between 1950 and 2010 are included in PESTIMAT: 160 fungicides; 160 herbicides; and 209 insecticides. When combined with duration and determinants of intensity, the metrics in PESTIMAT will make it possible to calculate exposure scores and to search for dose-effect relationships, an important criterion for causality judgment in epidemiology.
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