Comparable efficacy and good tolerability of 2-weekly vs 3- weekly docetaxel in castrate resistant metastatic prostate cancer

摘要

Background: Docetaxel administered every 3 weeks is the standard treatment protocol for patients with metastatic, castration resistant prostate cancer. In a prospective, phase 3study, we try to investigate the efficacy and tolerability of the 2-weekly administration of docetaxelas an alternative in case of intolerance to the 3-weekly regimen. Methods: Eligible patients had advanced prostate cancer (metastasis, a prostate-specific-antigen test result of more than 10.0 ng/mL, and WHO performance status score of 0–2), chemotherapy-naive, had undergone surgical or chemical castration, with adequate bone marrow, hepatic, and renal function and had been referred to a treatment center in Tanta university hospital. Enrolment and treatment were done between June 2010 and November 2012. Patients were assigned 75 mg/m2 docetaxel intravenously on day 1 of a 3-week cycle, or 45 mg/m2 docetaxel intravenously on days 1 and 15of a 4-week cycle. 10 mg oral prednisolone was administered daily to all patients. The primary endpoint was time to treatment failure (TTTF). Results: Twenty one patients were randomly assigned to the 2-weekly docetaxel group and 22 to the 3-weekly group and were included in the analysis. The 2-weekly administration was associated with non significant longer TTTF than was 3-weekly administration (5.8 months, 95% CI 3.9 –7.6 vs4.5 months, 2.6–6.3; p=0.568). In general, toxicities were similar between both arms. Thirty three percent of patients in the 2-weekly group and 45% in the 3-weekly group had grade 3–4 neutropenia (p=0.41). Patients who received 3-weekly docetaxel had more frequent neutropenic infections and nausea than did those who received 2-weekly docetaxel. Severe adverse events were seen more frequently in the 3-weekly docetaxel group than in the 2-weekly docetaxel group but without statistically significant difference (e.g. infections with neutropenia: p=0.62). There was no grade 3/4 neuropathy. Conclusion: The 2-weekly docetaxel regimen seems to be well tolerated in patients with castration resistant advanced prostate cancer and is a feasible option for men who present with comorbidities and who are judged unlikely to tolerate large single doses of docetaxel.