A Phase I/II Trial of Second-line Chemotherapy With Paclitaxel and Irinotecan in Fluoropyrimidine- and Platinum-Pretreated Advanced Gastric Cancer
In gastric cancer, several active chemotherapeutic agents have been introduced.
Fluoropyrimidine, platinum, taxane and topoisomerase inhibitor are the most commonly used
agents. Many available single or combination regimens are existed. But, there is no standard
palliative chemotherapy regimen as a first line treatment in unresectable advanced gastric
cancer. Thereafter there is also no standard second line regimen.
Usually the combination of fluoropyrimidine with platinum is used as a first line
chemotherapy (for example, 5-FU+cisplatin, capecitabine+cisplatin, S-1+ cisplatin,
5-FU+oxaliplatin). After failure with this combination, taxane-based regimen or
irinotecan-based regimen is usually used. But, as a second-line regimen, the combination of
topoisomerase inhibitor with taxane has not been fully evaluated until now.
In some studies using docetaxel and irinotecan combination in gastric cancer, the toxicity
is highly concerned. (Jatoi A et al. 2002, Lordick F etl al. 2003, S Enrech et al. 2003,
Chang HM et al. 2003) The combination of paclitaxel and irinotecan in gastric cancer is
evaluated in two studies until now as far as we know (K Kobayashi et al. 2006, Hecht JR et
al. 2003). These are phase I/II design and used this combination as first or second line
treatment of gastric cancer. The response rate is 29.6% and 27% respectively. In one study,
grade 3,4 hematologic toxicity is 33.3%. The dosing schedule is different between these two
In one study, paclitaxel 50mg/m2 and irinotecan 50mg/m2 is used day 1and day 8 every 3
weeks. In the other study, paclitaxel 100mg/m2 and irinotecan 225mg/m2 is used every 3
In these studies, the state of UGT1A1 polymorphism of enrolled patients has not been
reported. Recently it is well known that the UGT1A1 polymorphism influences on the toxicity
profile of irinotecan, e,g. myelosuppression and diarrhea. If a patient with UGT1A1*28 (7/7
homozygosity) is included in the low level of phase I period, the MTD of irinotecan might be
set up in low dose without showing sufficient efficacy.
We think that it may be of deserve to evaluate the efficacy of paclitaxel and irinotecan
combination regimen in gastric cancer patients and it is necessary to conduct phase I study
to find out the accurate MTD of this regimen after considering the UGT1A1 polymorphism of
So we designed this phase I/II study to evaluate the efficacy and toxicity of second-line
chemotherapy with paclitaxel and irinotecan in fluoropyrimidine and platinum-pretreated
advanced gastric cancer.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Dose-limiting toxicity (phase I part)
during first cycle (first 3 week)
Do-Youn Oh, MD, PhD
Seoul National University Hospital
Korea: Seoul National University Hospital