Docetaxel Dosing Every 2 Weeks May Be Superior to Current Standard Regimen in CRPC

Administration of docetaxel every 2 weeks in patients with castration-resistant prostate cancer (CRPC) was associated with significantly longer time to treatment failure (TTTF), improved overall survival (OS), and produced fewer adverse events compared with the standard every 3-week regimen, according to findings from a Finnish study published in the February issue of Lancet Oncology.

In this prospective, multicenter, randomized, phase III study, researchers with the Department of Oncology at Tampere University Hospital in Tampere, Finland, identified patients from 11 study centers in Finland, Ireland, and Sweden who had been treated between 2004 and 2009 for advanced metastatic prostate cancer. Patients who had undergone either surgical or chemical castration, had a PSA result >10 ng/mL, a WHO performance status score of 0-2, and had r eceived no prior chemotherapy other than estramustine were eligible for the study.

A total of 346 patients were selected for analysis and randomized to receive docetaxel every 2 weeks (50 mg/m2 on days 1 and 15 of a 4-week cycle [n = 170]) or every 3 weeks (75 mg/m2 on day 1 of a 3-week cycle [n = 176]). For each group, the median number of treatment cycles per patient was 6 (range 1—18 in the 2-weekly group and 1–29 in the 3-weekly group). Both groups also received 10 mg prednisolone.

TTTF, the study’s primary endpoint, was 5.6 months in the 2-weekly docetaxel group (95% CI, 5.0—6.2) and 4.9 months in the 3-weekly cohort (95% CI, 4.5–5.4), a statistically significant difference (hazard ratio [HR] = 1.3; 95% CI, 1.1–1.6; P = .014) (Table). Among the secondary endpoints, OS was 19.5 months in the 2-weekly group (95% CI, 15.9—23.1) versus 17 months in the 3-weekly group (95% CI, 15.0–19.1), which was also statistically significant (HR = 1.4; 95% CI, 1.1–1.8; P = .021), and time to progression was 15.8 months (95% CI, 13.6—18.1) and 14.6 months (95% CI, 13.2–16.0), respectively (HR = 1.3; 95% CI, 1.0–1.6; P = .047). The researchers reported that the OS finding was unexpected, suggesting that “more frequent docetaxel dosing might improve tolerability, efficacy, or both.”

Table. Summary of Primary and

Secondary Outcomes

2-weekly

docetaxel

(n=170)

3-weekly

docetaxel

(n=176)

P value

Median months to TTTF (95% CI)

5.6

(5.0-6.2)

4.9

(4.5-5.4)

.014

Median months to TTP or death

(95% CI)

15.8 (13.6-18.1)

14.6 (13.2-16.0)

.047

Median months to overall survival (95% CI)

19.5 (15.9-23.1)

17.0 (15.0-19.1)

.021

Medians and 95% CIs are estimated values from Kaplan-Meier analyses. PSA indicates prostate-specific antigen; TTP, time to progression; TTTF, time to treatment failure.

Treatment safety was another important consideration in the study, because most deaths from advanced prostate cancer occur in men ≥75 years of age, many of whom have comorbidities. The incidence of grade 3-4 neutropenia was 36% in the 2-weekly group (n = 61) and 53% (n = 93) in the 3-weekly group (P < .0001). Other adverse events (leucopenia and neutropenic infections) were also seen more frequently in the 3-weekly group. The number of dose reductions did not differ between the two groups. Quality of life, as gauged by functional assessment of cancer therapy—prostate (FACT-P) questionnaires administered at baseline and during and after treatment, was also similar between both cohorts.

Researchers concluded that “two-weekly docetaxel seems a feasible option for men who present with comorbidities and who are judged unlikely to tolerate large single doses of docetaxel.”

Kellokumpu-Lehtinen P-L, Harmenberg U, Joensuu T, et al. 2-weekly versus 3-weekly docetaxel to treat castration-resistant advanced prostate cancer: a randomised, phase 3 trial. Lancet Oncol. 2013;14(2):117-124.