R
Roger
Guest
J Clin Oncol. 2002 Mar 1;20(5):1182-91.
Irinotecan plus gemcitabine induces both radiographic and CA 19-9 tumor marker responses in patients
with previously untreated advanced pancreatic cancer.
H. Lee Moffitt Cancer Center, University of South Florida, Gastrointestinal Program Office, Tampa,
FL 33612, USA.
PURPOSE: This phase II, multicenter, open-label, single-arm study evaluated the efficacy and safety
of irinotecan and gemcitabine as combination chemotherapy for previously untreated patients with
unresectable or metastatic pancreatic cancer.
PATIENTS AND METHODS: Patients received repeated 21-day cycles at starting doses of gemcitabine
1,000 mg/m(2) over 30 minutes followed immediately by irinotecan 100 mg/m(2) over 90 minutes, both
given intravenously on days 1 and 8. Patients were evaluated for objective tumor response, changes
in the serum tumor marker CA 19-9, time to tumor progression (TTP), survival, and safety.
RESULTS: Forty-five patients were treated. Eleven patients (24%) had 50% or greater reductions in
tumor area. These were confirmed one cycle later in nine patients (response rate, 20%; 95%
confidence interval, 8% to 32%). Among 44 patients with baseline CA 19-9 determinations, CA 19-9
decreased during therapy in 22 patients (50%) and was reduced by 50% or more in 13 patients (30%).
Median TTP [time to progression] was 2.8 months (range, 0.3 to 10.8 months). There were significant
(P <.001) correlations between proportional changes in CA 19-9 and radiographic changes in tumor
area with regard to extent of change (r =.67), timing of minimum on-study values (r
=.85), and tumor progression (r =.89). Median survival was 5.7 months
(range, 0.4 to 19.4+ months), and the 1-year survival rate was 27%. Severe toxicities were uncommon
and primarily limited to grade 4 neutropenia (2%), grade 4 vomiting (2%), and grade 3 diarrhea (7%).
CONCLUSION: Irinotecan/gemcitabine is a new combination that offers encouraging activity in terms of
radiographic and CA 19-9 response and notable 1-year survival in pancreatic cancer. The regimen was
well tolerated, with minimal grade 3 and 4 toxicities and excellent maintenance of planned dose-
intensity.
Irinotecan plus gemcitabine induces both radiographic and CA 19-9 tumor marker responses in patients
with previously untreated advanced pancreatic cancer.
H. Lee Moffitt Cancer Center, University of South Florida, Gastrointestinal Program Office, Tampa,
FL 33612, USA.
PURPOSE: This phase II, multicenter, open-label, single-arm study evaluated the efficacy and safety
of irinotecan and gemcitabine as combination chemotherapy for previously untreated patients with
unresectable or metastatic pancreatic cancer.
PATIENTS AND METHODS: Patients received repeated 21-day cycles at starting doses of gemcitabine
1,000 mg/m(2) over 30 minutes followed immediately by irinotecan 100 mg/m(2) over 90 minutes, both
given intravenously on days 1 and 8. Patients were evaluated for objective tumor response, changes
in the serum tumor marker CA 19-9, time to tumor progression (TTP), survival, and safety.
RESULTS: Forty-five patients were treated. Eleven patients (24%) had 50% or greater reductions in
tumor area. These were confirmed one cycle later in nine patients (response rate, 20%; 95%
confidence interval, 8% to 32%). Among 44 patients with baseline CA 19-9 determinations, CA 19-9
decreased during therapy in 22 patients (50%) and was reduced by 50% or more in 13 patients (30%).
Median TTP [time to progression] was 2.8 months (range, 0.3 to 10.8 months). There were significant
(P <.001) correlations between proportional changes in CA 19-9 and radiographic changes in tumor
area with regard to extent of change (r =.67), timing of minimum on-study values (r
=.85), and tumor progression (r =.89). Median survival was 5.7 months
(range, 0.4 to 19.4+ months), and the 1-year survival rate was 27%. Severe toxicities were uncommon
and primarily limited to grade 4 neutropenia (2%), grade 4 vomiting (2%), and grade 3 diarrhea (7%).
CONCLUSION: Irinotecan/gemcitabine is a new combination that offers encouraging activity in terms of
radiographic and CA 19-9 response and notable 1-year survival in pancreatic cancer. The regimen was
well tolerated, with minimal grade 3 and 4 toxicities and excellent maintenance of planned dose-
intensity.