Docetaxel every 2 weeks (at a lower dose) or every 3 weeks (at the standard dose)


A study by a team of Finnish investigators has suggested that treating patients with metastatic, castration-resistant prostate cancer (mCRPC) with docetaxel chemotherapy every 2 weeks may have better outcomes and fewer side effects than the use of the currently recommended regimen, in which patients are dosed once every 3 weeks.

The new paper by Kellokumpu-Lehtinen et al., just published on line in Lancet Oncology, describes a prospective, multi-center, randomized, clinical trial designed to compare the efficacy and safety of two different docetaxel regimens described below.

All eligible patients had to have mCRPC, a PSA level > 10.0 ng/ml, and a WHO performance status of 0–2; they must have had some form of androgen deprivation therapy (ADT), in the form of an orchiectomy or a pharmacotherapeutic form of ADT; and they must have received no chemotherapy (other than estramustine). Patient enrollment and treatment was carried out between March 1, 2004, and May 31, 2009.

Patients were randomized to treatment with one or other of the following regimens:

  • Regimen A: Docetaxel (75 mg/m2) administered intravenously on day 1 of a 3-week cycle + prednisolone (10 mg/day p.o.) — the standard regimen
  • Regimen B: Docetaxel (50 mg/m2) administered intravenously on days 1 and 15 of a 4-week cycle + prednisolone (10 mg/day p.o.) — the alternate regimen

The primary study endpoint was time to treatment failure (TTTF). It is not clear from the abstract of the paper or from the trial description on the ClinicalTrials.gov web site exactly how TTTF was assessed, but we would assume that it had to include PSA progression and (probably) other factors such as increasing bone pain and spread of metastases.

Here are the study’s key findings:

  • 184 patients were randomly assigned to Regimen A, and 176 of these patients were included in the analysis.
  • 177 patients were randomly assigned to Regimen B and 170 of these patients were included in the analysis.
  • For patients on Regimen A
    • Median TTTF was 4.9 months (range, 4.5 to 5.4 months).
    • Grade 3 or 4 neutropenia was observed in 93/176 patients (53 percent).
    • Grade 3 or 4 leukopenia was observed in 51/176 patients (29 percent).
    • Grade 3 or 4 febrile neutropenia was observed in 25/176 patients (14 percent).
    • Neutropenic infections of any grade were observed in 43/176 patients (24 percent).
  • For patients on Regimen B
    • Median TTTF was 5.6 months (range, 5.0 to 6.2 months).
    • Grade 3 or 4 neutropenia was observed in 61/170 patients (36 percent).
    • Grade 3 or 4 leukopenia was observed in 22/170 patients (13 percent).
    • Grade 3 or 4 febrile neutropenia was observed in 6/170 patients (4 percent).
    • Neutropenic infections of any grade were observed in 11/170 patients (6 percent).

It is not apparent from the abstract of this paper why the eight patients randomized to Regimen A or the seven patients randomized to Regimen B were excluded from the analysis. Nor is it evident whether their exclusion would have made a significant difference to the reported outcomes.

The authors conclude that, “Administration of docetaxel every 2 weeks seems to be well tolerated in patients with [mCRPC] and could be a useful option when 3-weekly single-dose administration is unlikely to be tolerated.”

The “New” Prostate Cancer InfoLink would consider that this difference in TTTF and risk for side effects is statistically and clinically significant, and suggests that the study needs to be repeated in a somewhat larger trial to see if this result can be confirmed. While it would clearly be difficult for some patients to adapt to treatment every 2 weeks as opposed to every 3 weeks, this difficulty could well be worth enduring if the TTTF were to be extended (apparently by about 10 percent) and the risk of serious side effects was to be reduced by about half. It would also be interesting to know if the 2-weekly regimen had any impact on overall survival (given the lower risk for complications like febrile neutropenia).

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