Gemzar

Clinical Pharmacology

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Clinical Pharmacology

Gemzar

Pancreatic Cancer — Data from 2 clinical trials evaluated the use of Gemzar in patients with locally advanced or metastatic pancreatic cancer. The first trial compared Gemzar to 5-Fluorouracil (5-FU) in patients who had received no prior chemotherapy. A second trial studied the use of Gemzar in pancreatic cancer patients previously treated with 5-FU or a 5-FU-containing regimen. In both studies, the first cycle of Gemzar was administered intravenously at a dose of 1000 mg/m² over 30 minutes once weekly for up to 7 weeks (or until toxicity necessitated holding a dose) followed by a week of rest from treatment with Gemzar. Subsequent cycles consisted of injections once weekly for 3 consecutive weeks out of every 4 weeks.

The primary efficacy parameter in these studies was "clinical benefit response," which is a measure of clinical improvement based on analgesic consumption, pain intensity, performance status, and weight change. Definitions for improvement in these variables were formulated prospectively during the design of the 2 trials. A patient was considered a clinical benefit responder if either:

i) the patient showed a ≥ 50% reduction in pain intensity (Memorial Pain Assessment Card) or analgesic consumption, or a 20-point or greater improvement in performance status (Karnofsky Performance Status) for a period of at least 4 consecutive weeks, without showing any sustained worsening in any of the other parameters. Sustained worsening was defined as 4 consecutive weeks with either any increase in pain intensity or analgesic consumption or a 20-point decrease in performance status occurring during the first 12 weeks of therapy. OR:

ii) the patient was stable on all of the aforementioned parameters, and showed a marked, sustained weight gain (≥ 7% increase maintained for ≥ 4 weeks) not due to fluid accumulation.

The first study was a multi-center (17 sites in US and Canada), prospective, single-blinded, two-arm, randomized, comparison of Gemzar and 5-FU in patients with locally advanced or metastatic pancreatic cancer who had received no prior treatment with chemotherapy. 5-FU was administered intravenously at a weekly dose of 600 mg/m² for 30 minutes. The results from this randomized trial are shown in Table 6. Patients treated with Gemzar had statistically significant increases in clinical benefit response, survival, and time to disease progression compared to 5-FU. The Kaplan-Meier curve for survival is shown in Figure 4. No confirmed objective tumor responses were observed with either treatment.

Table 6: Gemzar Versus 5-FU in Pancreatic Cancer

	Gemzar	5-FU
Number of patients	63	63
Male	34	34
Female	29	29
Median age	62 years	61 years
Range	37 to 79	36 to 77
Stage IV disease	71.4%	76.2%
Baseline KPS^a ≥ 70	69.8%	68.3%
Clinical benefit response	22.2%	4.8%	p=0.004^e
	(N^c=14)	(N=3)
Survival			p=0.0009
Median	5.7 months	4.2 months
6-month probability^b	(N=30) 46%	(N=19) 29%
9-month probability^b	(N=14) 24%	(N=4) 5%
1-year probability^b	(N=9) 18%	(N=2) 2%
Range	0.2 to 18.6 months	0.4 to 15.1+^d 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+^d to 9.4 months	0.1 to 12.0+^d months
95% C.I. of the median	1.9 to 3.4 months	0.9 to 1.1 months
^a Karnofsky Performance Status.
^b Kaplan-Meier estimates.
^c N=number of patients.
^d No progression at last visit; remains alive.
^e The p-value for clinical benefit response was calculated using the two-sided test for difference in binomial proportions. All other p-values were calculated using the Log rank test for difference in overall time to an event.