68.3%
Clinical benefit response
22.2%
(N†=14)
4.8%
(N=3)
p=0.004‡
Survival
p=0.0009
Median
5.7 months
4.2 months
6–month probability§
(N=30) 46%
(N=19) 29%
9–month probability§
(N=14) 24%
(N=4) 5%
1–year probability§
(N=9) 18%
(N=2) 2%
Range
0.2 to 18.6 months
0.4 to 15.1+¶ months
95% C.I. of the median
4.7 to 6.9 months
3.1 to 5.1 months
Time to Disease Progression
p=0.0013
Median
2.1 months
0.9 months
Range
0.1+¶ to 9.4 months
0.1 to 12.0+¶ months
95% C.I. of the median
1.9 to 3.4 months
0.9 to 1.1 months
Clinical benefit response was achieved by 14 patients treated with Gemzar and 3 patients treated with 5–FU. One patient on the Gemzar arm showed improvement in all 3 primary parameters (pain intensity, analgesic consumption, and performance status). Eleven patients on the Gemzar arm and 2 patients on the 5–FU arm showed improvement in analgesic consumption and/or pain intensity with stable performance status. Two patients on the Gemzar arm showed improvement in analgesic consumption or pain intensity with improvement in performance status. One patient on the 5–FU arm was stable with regard to pain intensity and analgesic consumption with improvement in performance status. No patient on either arm achieved a clinical benefit response based on weight gain.
Figure 4: Kaplan–Meier Survival Curve
The second trial was a multicenter (17 US and Canadian centers), open–label study of Gemzar in 63 patients with advanced pancreatic cancer previously treated with 5–FU or a 5–FU–containing regimen. The study showed a clinical benefit response rate of 27% and median survival of 3.9 months.
Other Clinical Studies
When Gemzar was administered more frequently than once weekly or with infusions longer than 60 minutes, increased toxicity was observed. Results of a Phase 1 study of Gemzar to assess the maximum tolerated dose (MTD) on a daily x 5 schedule showed that patients developed significant hypotension and severe flu–like symptoms that were intolerable at doses above 10 mg/m2. The incidence and severity of these events were dose–related. Other Phase 1 studies using a twice–weekly schedule reached MTDs of only 65 mg/m2 (30–minute infusion) and 150 mg/m2 (5–minute bolus). The dose–limiting toxicities were thrombocytopenia and flu–like symptoms, particularly asthenia. In a Phase 1 study to assess the maximum tolerated infusion time, clinically significant toxicity, defined as myelosuppression, was seen with weekly doses of 300 mg/m2 at or above a 270–minute infusion time. The half–life of gemcitabine is influenced by the length of the infusion (see CLINICAL PHARM |
