Number Of Docetaxel Cycles Key To Mainsail OS Outcomes

Number of docetaxel cycles linked to overall survival in the Mainsail metastatic castration-resistant prostate cancer trial

medwireNews: The overall survival (OS) of patients with metastatic, castration-resistant prostate cancer treated with docetaxel is significantly associated with the number of treatment cycles they receive, suggests post hoc analysis of the Mainsail trial.

Describing the relationship as a “robust and independent effect”, the researchers say the findings have “important implications for the optimal administration of docetaxel chemotherapy”.

They therefore recommend in JAMA Oncology: “To provide the greatest survival gain by docetaxel chemotherapy, those patients who appear to benefit by clinical or radiological evidence and who tolerate the chemotherapy well should continue beyond 6, and perhaps even beyond 10 cycles, until disease progression occurs or unacceptable adverse effects dictate otherwise.”

The phase III Mainsail trial showed that combined docetaxel, prednisone and lenalidomide (DPL) was inferior to docetaxel, prednisone and placebo (DP) for OS in 1059 patients with metastatic castration-resistant prostate cancer, write Ronald de Wit, from Erasmus MC Cancer Institute in Rotterdam, the Netherlands, and co-authors.

They explain that increased toxicity associated with the DPL combination resulted in patients receiving a median of six docetaxel cycles compared with a median of eight cycles for patients randomly assigned to receive the DP regime.

Analysis of the intention-to-treat population confirmed that OS was significantly higher for patients in both the DPL and DP groups receiving eight or more docetaxel cycles than those given fewer cycles, with a similar pattern using a cut off of six and 10 cycles.

Initial multivariate analysis taking into consideration a raft of confounding factors confirmed that OS was significantly associated with treatment, being better with DP than DPL, at a significant hazard ratio (HR) of 1.626.

But when the number of docetaxel cycles was added into the multivariate analysis, receipt of eight or more cycles was a significant and independent predictor of superior OS, with a HR of 1.909 versus fewer cycles, and type of treatment was no longer a significant factor.

OS after docetaxel was also significantly associated with baseline measures of lactose dehydrogenase, albumin and haemoglobin, and ECOG performance status.

Sensitivity analysis on a subgroup of patients who received more than four cycles of docetaxel and did not stop treatment because of disease progression confirmed that treatment arm did not significantly influence OS.

When the treatment arms were combined, patients who received at least 10 cycles of docetaxel had significantly longer OS than those given 8–10 or 5–7 cycles (median 33.0 vs 26.9 and 22.8 months, respectively). And this pattern was true when the two treatment arms were assessed separately, the researchers say.

“Enhanced toxic effects by the addition of lenalidomide to docetaxel in the experimental arm resulted in a lower cumulative dose of docetaxel, reflected by fewer docetaxel cycles administered and more frequent dose reductions”, they summarise, adding that the findings “strongly suggest that the differences in the cumulative docetaxel exposure caused the worse OS in the experimental arm.”

Ronald de Wit et al therefore conclude: “These findings imply that the total dose of docetaxel, as reflected in [the total] number of cycles achieved, contributes to the eventual survival gain by chemotherapy in the patient population with [metastatic castration-resistant prostate cancer].”


de Morrée ES, Vogelzang NJ, Petrylak DP, et al. Association of survival benefit with docetaxel in prostate cancer and total number of cycles administered. A post hoc analysis of the Mainsail Study. JAMA Oncol; Advance online publication 25 August 2016


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