The evidence for the 2 weekly docetaxel for castrate-resistant advanced prostate cancer comes from a small Phase 3 prospective, multicentre, randomised trial by Kellokumpi-Lehtinen et al.r This trial examined the efficacy and safety of 2-weekly docetaxel compared to 3-weekly docetaxel. There had been no previous comparison of this regimen in a randomised trial as first line chemotherapy for advanced prostate cancer.
The trial randomly assigned 176 patients to receive 75 mg/m2 docetaxel on day 1 of a 3-week cycle and 170 patients to receive 50 mg/m2 docetaxel on days 1 and 15 of a 4-week cycle. Both cohorts received 10 mg oral prednisolone daily.
The primary endpoint was time to treatment failure (TTTF). It was powered to determine a significant advantage in TTTF of 2 months (from 5 to 7 months). The secondary endpoints were tumour response, PSA response, overall survival (OS), and time to disease progression.
This regimen offers an option for patients who are unlikely to tolerate large single doses of docetaxel in the standard 3 weekly protocol.
The median TTTF was 5.6 months and 4.9 months in the 2-weekly and 3-weekly arms respectively (HR 1.3, 95% CI, 1.1-1.6, p=0.014). Thus primary endpoint was actually not met.
The subgroup analysis showed the TTTF was longer if the patients were younger (<65 years) with a WHO performance status of 0 and PSA less than median 114 ng/mL.
The TTP and OS were longer in the 2-weekly group compared to the 3-weekly group. There were no differences between the two arms for tumour and PSA response.
The quality of life features at the end of treatment in both treatment arms were similar.
A: Time to treatment failure. B: Time to progression. C: Overall survival
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There was a lower incidence of Grade 3-4 neutropenia in the 2-weekly group, 36%, versus 53% in the 3-weekly group. Similarly there was a higher incidence of myelosuppression, and neutropenic infection, and nausea in the 3-weekly cohort compared to the 2-weekly treatment.r
© Lancet Oncol 2013