Paclitaxel and Irinotecan in Advanced Gastric Cancer
Condition: Advanced Gastric Cancer
MeSH terms: Stomach Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      -  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) in advanced gastric cancer.

        -  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.

        -  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.
    

Detailed description: 
      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 studies.

      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 weeks.

      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
      patients.

      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.
    

Intervention name(s): Paclitaxel and irinotecan
Intervention type(s): Drug
Intervention description(s): In phase I part, Level Paclitaxel (mg/m²) Irinotecan (mg/m²)
100 100
100 120
135 120
135 160
every 3 week
Intervention MeSH terms: Paclitaxel; Irinotecan
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: advanced gastric cancer; 1st-line failure