Phase I/II Study of Paclitaxel Plus CPT-11 in Pts. With 2nd Line Chemotherapy of Inoperable or Recurrent GC.

Phase I/II Study of Biweekly Administration Regimen of Paclitaxel Combined With CPT-11 in Patients With Second Line Chemotherapy of Inoperable or Recurrent Gastric Cancer(GC).

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.

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