Gemcitabine (Gemzar) and irinotecan (CPT-II, Camptosar) are active cytotoxi
c drugs against pancreatic cancer: Preclinical data evaluating the combinat
ion of gemcitabine and irinotecan suggest dose-dependent synergistic intera
ctions in SCOG small-cell lung cancer and MCF-7 breast cancer cell lines. T
wo phase I trials of this combination have been reported to date: the day 1
and 8 every-3-week schedule (IrinoGem trial), and the day 1, 8, and 15 eve
ry-4-week schedule (MSKCC trial). Both trials aimed to determine the maximu
m tolerated dose of irinotecan when administered as a 90-minute IV infusion
either immediately after (IrinoGem) or before or immediately after (MSKCC)
gemcitabine at 1,000 mg/m(2) by 30-minute IV infusion lit patients with so
lid tumors. The achieved maximum tolerated dose of IrinoGem has a higher do
se intensity of irinotecan (100 mg/m(2) on days 1 and 8, every-3-week cycle
) compared with the MSKCC schedule (60 mg/m2 on days 1, 8, and 15, every-4-
week trial). In IrinoGem, two of three previously untreated metastatic meta
static cancer patients had durable radiologic partial responses. The third
had stable disease with clinical benefit for eight cycles. In addition, a p
atient with metastatic adenocarcinoma of unknown primary - potentially panc
reatic - has had a durable response and is alive more than 30 months after
the diagnosis. Preliminary results of a 45-patient multicenter phase II tri
al with IrinoGem ill advanced and metastatic pancreas cancer were recently
reported. Toxicity was modest with no toxic deaths or neutropenic fever, Ra
diologic response rate was 20% of patients (9 out of 45) and a CA 19-9 decr
ease of more than 50% from baseline values occurred in 32.5% of patients (1
3 out of 40). Median survival was 6 months (range: 0.9 to 12.2+ months) and
median time to treatment failure was 2.9 months (range: 0.1 to 11.3+ month
s). A pivotal international multicenter phase III trial comparing IrinoGem
to single-agent gemcitabine in advanced and metastatic pancreas cancer is o
ngoing.