Drug Interactions
When Gemzar (1250 mg/m2 on Days 1 and 8) and cisplatin (75 mg/m2 on Day 1) were administered in NSCLC patients, the clearance of gemcitabine on Day 1 was 128 L/hr/m2 and on Day 8 was 107 L/hr/m2. The clearance of cisplatin in the same study was reported to be 3.94 mL/min/m2 with a corresponding half–life of 134 hours (see Drug Interactions under PRECAUTIONS). Analysis of data from metastatic breast cancer patients shows that, on average, Gemzar has little or no effect on the pharmacokinetics (clearance and half–life) of paclitaxel and paclitaxel has little or no effect on the pharmacokinetics of Gemzar. Data from NSCLC patients demonstrate that Gemzar and carboplatin given in combination does not alter the pharmacokinetics of Gemzar or carboplatin compared to administration of either single-agent. However, due to wide confidence intervals and small sample size, interpatient variability may be observed.
CLINICAL STUDIES
Ovarian Cancer
Gemzar was studied in a randomized Phase 3 study of 356 patients with advanced ovarian cancer that had relapsed at least 6 months after first–line platinum–based therapy. Patients were randomized to receive either Gemzar 1000 mg/m2 on Days 1 and 8 of a 21–day cycle and carboplatin AUC 4 administered after Gemzar on Day 1 of each cycle or single–agent carboplatin AUC 5 administered on Day 1 of each 21–day cycle as the control arm. The primary endpoint of this study was progression free survival (PFS).
Patient characteristics are shown in Table 2. The addition of Gemzar to carboplatin resulted in statistically significant improvement in PFS and overall response rate as shown in Table 3 and Figure 1. Approximately 75% of patients in each arm received poststudy chemotherapy. Only 13 of 120 patients with documented poststudy chemotherapy regimen in the carboplatin arm received Gemzar after progression. There was not a significant difference in overall survival between arms.
Table 2: Gemzar Plus Carboplatin Versus Carboplatin in Ovarian Cancer – Baseline Demographics and Clinical Characteristics *
Nine patients (5 on the Gemzar plus carboplatin arm and 4 on the carboplatin arm) did not have baseline Eastern Cooperative Oncology Group (ECOG) performance status recorded.
Three patients (2 on the Gemzar plus carboplatin arm and 1 on the carboplatin arm) had a platinum–free interval of less than 6 months.
Gemzar/Carboplatin
Carboplatin
Number of randomized patients
178
178
Median age, years
59
58
Range
36 to 78
21 to 81
Baseline ECOG performance status 0–1*
94%
95%
Disease Status
eva luable
7.9%
2.8%
Bidimensionally measurable
91.6%
95.5%
Platinum–free interval†
6–12 months
39.9%
39.9%
>12 months
59.0%
59.6%
First–line therapy
Platinum–taxane combination
70.2%
71.3%
Platinum–non–taxane combination
28.7%
27.5%
Platinum monotherapy
1.1%
