phase i/ii study of paclitaxel plus cpt-11 in pts. with 2nd line chemotherapy of inoperable or recurrent gc.

Conditions: Gastric Cancer

Summary: a phase i/ii study is conducted to determine the maximum-tolerated dose (mtd), dose-limiting toxicity (dlt), and efficacy of a combination chemotherapy using cpt-11 and paclitaxel in pre-treated patients with metastatic gastric cancer. the usefulness of the this regimen is evaluated by response rate, median survival time, and progression free survival.

patients with pre-treated measurable metastatic gastric cancer were included in this trial. patients received this combination chemotherapy repeated every 28 days until progression disease. starting dose (dose level 1) were cpt-11 80 mg/m2 on day 1 and 15, paclitaxel 60 mg/m2 on day 1 and 15. dlt was defined as follows (according to nci-ctc version 2.0); grade 4 neutropenia, thrombocytopenia(≥25000), grade 3 neutropenia accompanied fever (\>38℃) , and grade 3 non-hematological toxicity (except for nausea, vomit, appetite loss , general fatigue, alopecia). maximal tolerated dose (mtd) is determined when the incidence of critical toxicity exceeds 50% at a certain dose level. response rate will be calculated according to recist criteria.

Eligibility criteria:
inclusion criteria: * histologically confirmed metastatic or recurrent gastric cancer with prior treatment for advanced disease. * patients who have received 1cycle cancer therapy (radiotherapy, chemotherapy or chemoradiotherapy) given \> 4 weeks prior to the beginning of study therapy * at least one measurable lesion according to the recist criteria. minimum indicator lesion size: \> 10 mm measured by spiral ct or \>20mm measured by conventional techniques(except for phase i setting). * patients aged between 20 and 75 years, inclusive, at the time of acquisition of informed consent * patients with performance status(ecog) 0 to 2 * abnormal hematologic values (wbc ≥ 3.5 x 109/l, hemoglobin ≥ 9.0g/dl, platelet count ≥ 100 x 109/l) * serum cleatinine ≤ 1.5mg/dl * serum bilirubin ≤ 1.5mg/dl. alt, ast ≤ 2.0 x upper normal limit (or ≤ 3 x upper normal limit in the case of liver metastases) * normal ecg * life expectancy ≥ 3 months * patients who have given written informed consent to participate in this study exclusion criteria: * patients with active multiple cancers; or even if the multiple cancers are metachronous, have a disease-free period of less than 5 years (but excluding cancer in situ and skin cancer) (except for phase i setting) * serious, uncontrolled, concurrent infection(s) or illness(es) * patients with no serious concurrent complications (such as heart disease, intestinal pneumonia) * patients with liver cirrhosis * patients with fresh hemorrhage from the gastrointestinal tract * patients with poorly controlled diabetes or are treated by continuous use of insulin * patients with concurrent psychiatric disease or psychotic symptoms, and judged to have difficulties participating in the study * patients with retention of body fluid(pleural effusion, ascites, pericardial effusion) necessitating treatment * patients with diarrhea (watery stool) * patients with infection, intestinal palsy or intestinal occlusion * patients with brain metastasis * patients with gilbert syndrome * patients who have experienced serious drug allergy in the past * patients who are pregnant and lactating or hope to become pregnant during the study period * patients with prior taxan (paclitaxel, docetaxel) or cpt-11 treatment * patients with neuropathy ≥ grade 2 * others, patients judged by the investigator or subinvestigator to be inappropriate as subject