Docetaxel (Page 10 of 12)

14.4 Hormone Refractory Prostate Cancer

The safety and efficacy of another formulation of docetaxel in combination with prednisone in patients with androgen independent (hormone refractory) metastatic 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 19 and Figure 5.

Table 19 — Efficacy of Docetaxel in the Treatment of Patients with Androgen Independent (Hormone Refractory) Metastatic Prostate Cancer (Intent-to-Treat Analysis)
Docetaxel + Prednisone every 3 weeks Mitoxantrone + Prednisone every 3 weeks
*
Stratified log rank test. Threshold for statistical significance = 0.0175 because of 3 arms.

Number of patients

335

337

Median survival (months)

18.9

16.5

95% CI

(17.0 to 21.2)

(14.4 to 18.6)

Hazard ratio

0.761

95% CI

(0.619 to 0.936)

p-value *

0.0094

Figure 5 — TAX327 Survival K-M Curves

Docetaxel Injection
(click image for full-size original)

14.5 Gastric Adenocarcinoma

A multicenter, open-label, randomized trial was conducted to evaluate the safety and efficacy of another formulation of docetaxel for the treatment of patients with advanced gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who had not received prior chemotherapy for advanced disease. A total of 445 patients with KPS >70 were treated with either docetaxel (T) (75 mg/m 2 on day 1) in combination with cisplatin (C) (75 mg/m 2 on day 1) and fluorouracil (F) (750 mg/m 2 per day for 5 days) or cisplatin (100 mg/m 2 on day 1) and fluorouracil (1000 mg/m 2 per day for 5 days). The length of a treatment cycle was 3 weeks for the TCF arm and 4 weeks for the CF arm. The demographic characteristics were balanced between the two treatment arms. The median age was 55 years, 71% were male, 71% were Caucasian, 24% were 65 years of age or older, 19% had a prior curative surgery and 12% had palliative surgery. The median number of cycles administered per patient was 6 (with a range of 1 to 16) for the TCF arm compared to 4 (with a range of 1 to 12) for the CF arm. Time to progression (TTP) was the primary endpoint and was defined as time from randomization to disease progression or death from any cause within 12 weeks of the last evaluable tumor assessment or within 12 weeks of the first infusion of study drugs for patients with no evaluable tumor assessment after randomization. The hazard ratio (HR) for TTP was 1.47 (CF/TCF, 95% CI: 1.19 to 1.83) with a significantly longer TTP (p=0.0004) in the TCF arm. Approximately 75% of patients had died at the time of this analysis. Overall survival was significantly longer (p=0.0201) in the TCF arm with a HR of 1.29 (95% CI: 1.04 to 1.61). Efficacy results are summarized in Table 20 and Figures 6 and 7.

Table 20 — Efficacy of Docetaxel in the treatment of patients with gastric adenocarcinoma
Endpoint TCF n=221 CF n=224
*
For the hazard ratio (TCF/CF), values < 1.00 favor the docetaxel arm.
Unstratified log-rank test

Median TTP (months)

5.6

3.7

(95%CI)

(4.86 to 5.91)

(3.45 to 4.47)

Hazard ratio *

0.68

(95%CI)

(0.55 to 0.84)

p-value

0.0004

Median survival (months)

9.2

8.6

(95%CI)

(8.38 to 10.58)

(7.16 to 9.46)

Hazard ratio *

0.77

(95%CI)

(0.62 to 0.96)

p-value

0.0201

Overall Response Rate (CR+PR) (%)

36.7

25.4

p-value

0.0106

Subgroup analyses were consistent with the overall results across age, gender and race.

Figure 6 — Gastric Cancer Study (TAX325) Time to Progression K-M Curve

Docetaxel
(click image for full-size original)

Figure 7 — Gastric Cancer Study (TAX325) Survival K-M Curve

Docetaxel
(click image for full-size original)

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