Survival was monitored every three months after the patient completed treatment. Safety was monitored throughout the study and for 28 days after the last study treatment. Adverse events were graded www.selleckchem.com/products/CHIR-258.html according to the National Cancer Institute-Common Toxicity Criteria (NCI-CTC). Hand-foot syndrome was graded as in previous capecitabine studies.19 TTP and survival were analyzed by the Kaplan-Meier product limit method. Those who did not receive at least one dose of study medication or for whom no follow-up safety information was available were excluded from the safety analysis. RESULTS Patient characteristics Twenty-four patients (18 women and 6 men) were enrolled between June 2001 and December 2004. Patients who received at least one dose of CapGem were considered evaluable for efficacy and safety.

As shown in Table 1, the majority of patients (75%) had Stage IV disease and the most commonly affected metastatic sites were the liver (67%) and the lymph nodes (54%). Fourteen patients had undergone one or more type of surgery. Table 1 Patient Characteristics Treatment administration A median of four courses of treatment (range, 1-16 courses) were given. Reasons for discontinuing study treatment included disease progression (79%), toxicity (10%), or other reasons (11%). During Cycle 1, 96.7% (range, 86-100%) and 98.7% (range, 87-100%) of the planned dose of capecitabine and gemcitabine, respectively, were given. During Cycle 2, 95.1% (range, 83-100%) and 96.3% (range, 85-100%) of the planned doses of capecitabine and gemcitabine, respectively, were given.

Despite the need for dose modifications, 90% of patients received all three weeks of treatment with both drugs during the first two cycles of therapy. Efficacy Eight of the 24 patients (33%, 95% CI, 19-48%) had a partial response (PR) and ten patients (42%) had stable disease (SD) (investigator-determined responses, Table 2). The median TTP was 6.0 months (95% CI, 3.0-8.1 months), and the median overall survival was 16 months (95% CI, 13.8-18.3 months). The 1-year actuarial survival rate was 58% (Fig. 1). Efficacy data are shown in Table 2. Fig. I The median TTP was 6.0 months (95% CI, 3.0-8.1 months), and the median overall survival was 16 months (95% CI, 13.8-18.3 months). The 1-year actuarial survival rate was 58%. Table 2 Efficacy Data Safety Table 3 summarizes the toxicity observations.

Non-hematological adverse events (Grade 2 percentage/Grade 3 percentage) were: nausea Drug_discovery (25%/8%), hand-foot syndrome (17%/8%), general weakness (17%/8%), anorexia (17%/4%), stomatitis (13%/4%), vomiting (13%/4%), constipation (4%/4%), and diarrhea (4%/4%). Grade 3 neutropenia, anemia, and thrombocytopenia occurred in 13%, 8% and 8% of patients, respectively. Two patients developed febrile episodes. Grade 2 and Grade 3 hepatotoxicity developed in 8% and 8% of patients, respectively. No Grade 4 toxicity was seen.