DOCETAXEL (Page 17 of 20)

Combination Therapy with docetaxel for Chemotherapy-Naive NSCLC

In a randomized controlled trial (TAX326), 1218 patients with unresectable stage IIIB or IV NSCLC and no prior chemotherapy were randomized to receive one of three treatments: docetaxel 75 mg/m 2 as a 1 hour infusion immediately followed by cisplatin 75 mg/m 2 over 30 to 60 minutes every 3 weeks; vinorelbine 25 mg/m 2 administered over 6-10 minutes on days 1, 8, 15, 22 followed by cisplatin 100 mg/m 2 administered on day 1 of cycles repeated every 4 weeks; or a combination of docetaxel and carboplatin.

The primary efficacy endpoint was overall survival. Treatment with docetaxel+cisplatin did not result in a statistically significantly superior survival compared to vinorelbine+cisplatin (see table below). The 95% confidence interval of the hazard ratio (adjusted for interim analysis and multiple comparisons) shows that the addition of docetaxel to cisplatin results in an outcome ranging from a 6% inferior to a 26% superior survival compared to the addition of vinorelbine to cisplatin. The results of a further statistical analysis showed that at least (the lower bound of the 95% confidence interval) 62% of the known survival effect of vinorelbine when added to cisplatin (about a 2-month increase in median survival; Wozniak et al. JCO, 1998) was maintained. The efficacy data for the docetaxel+cisplatin arm and the comparator arm are summarized in Table 16.

Table 16: Survival Analysis of Docetaxel in Combination Therapy for Chemotherapy-Naive NSCLC
Comparison Docetaxel + Cisplatin n=408 Vinorelbine + Cisplatin n=405
From the superiority test (stratified log rank) comparing docetaxel + cisplatin to vinorelbine+cisplatin
Hazard ratio of docetaxel + cisplatin vs. vinorelbine + cisplatin. A hazard ratio of less than 1 indicates that docetaxel + cisplatin is associated with a longer survival.
Adjusted for interim analysis and multiple comparisons.
Kaplan-Meier Estimate of Median Survival 10.9 months 10.0 months
p-value * 0.122
Estimated Hazard Ratio 0.88
Adjusted 95% CI (0.74, 1.06)

The second comparison in the same three-arm study, vinorelbine+cisplatin versus docetaxel+carboplatin, did not demonstrate superior survival associated with the docetaxel arm (Kaplan-Meier estimate of median survival was 9.1 months for docetaxel +carboplatin compared to 10.0 months on the vinorelbine+cisplatin arm) and the docetaxel+carboplatin arm did not demonstrate preservation of at least 50% of the survival effect of vinorelbine added to cisplatin. Secondary endpoints evaluated in the trial included objective response and time to progression. There was no statistically significant difference between docetaxel+cisplatin and vinorelbine+cisplatin with respect to objective response and time to progression (see Table 17).

Table 17: Response and TTP Analysis of Docetaxel in Combination Therapy for Chemotherapy-Naive NSCLC
Endpoint Docetaxel + Cisplatin Vinorelbine + Cisplatin p-value
Adjusted for multiple comparisons.
Kaplan-Meier estimates.
Objective Response Rate 31.6% 24.4% Not Significant
(95% CI) * (26.5%, 36.8%) (19.8%, 29.2%)
Median Time to Progression 21.4 weeks (19.3, 24.6) 22.1 weeks (18.1, 25.6) Not Significant
(95% CI) *

14.4 Castration-Resistant Prostate Cancer

The safety and efficacy of docetaxel in combination with prednisone in patients with metastatic castration-resistant prostate cancer were evaluated in a randomized multicenter active control trial. A total of 1006 patients with Karnofsky Performance Status (KPS) ≥60 were randomized to the following treatment groups:

  • Docetaxel 75 mg/m 2 every 3 weeks for 10 cycles.
  • Docetaxel 30 mg/m 2 administered weekly for the first 5 weeks in a 6-week cycle for 5 cycles.
  • Mitoxantrone 12 mg/m 2 every 3 weeks for 10 cycles.

All 3 regimens were administered in combination with prednisone 5 mg twice daily, continuously.

In the docetaxel every three week arm, a statistically significant overall survival advantage was demonstrated compared to mitoxantrone. In the docetaxel weekly arm, no overall survival advantage was demonstrated compared to the mitoxantrone control arm. Efficacy results for the docetaxel every 3 week arm versus the control arm are summarized in Table 18 and Figure 5.

Table 18: Efficacy of Docetaxel in the Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer (Intent-to-Treat Analysis)
Docetaxel + Prednisone every 3 weeksMitoxantrone + Prednisone every 3 weeks
Stratified log rank test. Threshold for statistical significance = 0.0175 because of 3 arms.
Number of patients335337
Median survival (months)18.916.5
95% CI(17.0-21.2)(14.4-18.6)
Hazard ratio0.761
95% CI(0.619-0.936)
p-value *0.0094

Figure 5: TAX327 Survival K-M Curves

Docetaxel Injection
(click image for full-size original)

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