The adverse event profile for patients receiving TAXOL in combination with cisplatin in these studies was qualitatively consistent with that seen for the pooled analysis of data from 812 patients treated with single-agent TAXOL in 10 clinical studies. These adverse events and adverse events from the Phase 3 first-line ovarian carcinoma studies are described in the ADVERSE REACTIONS section in tabular (TABLES 10 and 11) and narrative form.

Second-Line Data: Data from 5, Phase 1 and 2 clinical studies (189 patients), a multicenter randomized Phase 3 study (407 patients), as well as an interim analysis of data from more than 300 patients enrolled in a treatment referral center program were used in support of the use of TAXOL in patients who have failed initial or subsequent chemotherapy for metastatic carcinoma of the ovary. Two of the Phase 2 studies (92 patients) utilized an initial dose of 135 to 170 mg/m² in most patients ( > 90%) administered over 24 hours by continuous infusion. Response rates in these 2 studies were 22% (95% CI, 11–37%) and 30% (95% CI, 18–46%) with a total of 6 complete and 18 partial responses in 92 patients. The median duration of overall response in these 2 studies measured from the first day of treatment was 7.2 months (range, 3.5–15.8 months) and 7.5 months (range, 5.3–17.4 months), respectively. The median survival was 8.1 months (range, 0.2–36.7 months) and 15.9 months (range, 1.8–34.5+ months).

The Phase 3 study had a bifactorial design and compared the efficacy and safety of TAXOL (paclitaxel), administered at 2 different doses (135 or 175 mg/m²) and schedules (3- or 24-hour infusion). The overall response rate for the 407 patients was 16.2% (95% CI, 12.8–20.2%), with 6 complete and 60 partial responses. Duration of response, measured from the first day of treatment was 8.3 months (range, 3.2–21.6 months). Median time to progression was 3.7 months (range, 0.1+ to 25.1+ months). Median survival was 11.5 months (range, 0.2 to 26.3+ months).

Response rates, median survival, and median time to progression for the 4 arms are given in the following table.

TABLE 3: EFFICACY IN THE PHASE 3 SECOND-LINE OVARIAN CARCINOMA STUDY

Analyses were performed as planned by the bifactorial study design described in the protocol, by comparing the 2 doses (135 or 175 mg/m²) irrespective of the schedule (3 or 24 hours) and the 2 schedules irrespective of dose. Patients receiving the 175 mg/m² dose had a response rate similar to that for those receiving the 135 mg/m² dose: 18% versus 14% (p=0.28). No difference in response rate was detected when comparing the 3-hour with the 24-hour infusion: 15% versus 17% (p=0.50). Patients receiving the 175 mg/m² dose of TAXOL had a longer time to progression than those receiving the 135 mg/m² dose: median 4.2 versus 3.1 months (p=0.03). The median time to progression for patients receiving the 3-hour versus the 24-hour infusion was 4.0 months versus 3.7 months, respectively. Median survival was 11.6 months in patients receiving the 175 mg/m² dose of TAXOL and 11.0 months in patients receiving the 135 mg/m² dose (p=0.92). Median survival was 11.7 months for patients receiving the 3-hour infusion of TAXOL and 11.2 months for patients receiving the 24-hour infusion (p=0.91). These statistical analyses should be viewed with caution because of the multiple comparisons made.

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