combination of pemetrexed (Alimta) and gemcitabine (Gemzar) is active in
pancreatic cancer with acceptable toxicity and a promising 32% 1-year survival
rate, according to an oral presentation at the 38th Annual Meeting of the
American Society of Clinical Oncology (abstract 499).
Pemetrexed is a multitargeted anti-folate shown to have
activity against pancreatic cancer in phase I and II trials. The combination of
pemetrexed with gem-citabine is synergistic in vitro and was broadly active in
a phase I study.
In this multicenter phase II trial, previously untreated
patients with histologically proven advanced pancreatic cancer received
gemcitabine, 1,250 mg/m2
over 30 minutes on days 1 and 8 of a 21-day cycle; pemetrexed, 500 mg/m2
over 10 minutes on day 8; and dexamethasone premedication to prevent rash.
Of 42 patients enrolled from September 1999 through November
2000, 41 were evaluable for response after receiving a total of 213 cycles
(range, 1 to 20 per patient; median, 4). Median age was 60 years (range, 34 to
79); 64% of patients were male; 95% had stage IV disease; 12% had received
prior fluorouracil. Most patients had a Karnofsky performance status of 80 or
90, and 67% had liver metastases.
"Beginning in December of 1999, folic acid and vitamin B12
were also given during a 2- to 7-day lead-in period, since earlier studies
showed that these supplements significantly reduce pemetrexed toxicity," said
presenter and lead author Hedy L. Kindler, MD, assistant professor of medicine,
University of Chicago.
Patients underwent a daily pain assessment and kept an
analgesic medication diary; they were seen weekly for history, physical,
weight, and performance status, and every 6 weeks they had a CT scan and a
CA19-9 test. There were six partial responses for an overall response rate of
12%, and 44% of patients had stable disease. Three additional patients had an
unconfirmed partial response. One-year survival was 32%. Median survival was
6.6 months, and median time to progression was 3.1 months.
Clinical benefit analysis was done on 30 patients, and 4
patients (13.3%) achieved a clinical benefit response (a composite of
performance status, analgesic consumption, pain intensity, and weight). "It is
noteworthy that the patients in this study were less symptomatic at baseline,
compared to those in a randomized gemcitabine study, which is why we may have
seen a lower clinical benefit response," Dr. Kindler said.