PFS and OS were analyzed by the Kaplan Meier method. Those patients who did not receive at least one dose of study medication or for whom no follow up safety information was available were excluded. Statistical Analysis The Simon optimal two stage design was chosen for sample size calculation. Drug screening libraries the expected number of patients for accrual in this study was calculated to reject a 10% response rate in favor of a target response rate of 30%. This condition allows a significance level of 0.05 with a statistical power of 90%. The preliminary activity of this new combination will be assessed enrolling 9 patients. If there was ! 1 response, accrual needed to be terminated. Otherwise, 21 additional patients need to be entered in the second chemical catalogs stage to achieve a target sample size of 30 evaluable patients for tumor response. If more than 4 responses were observed in these 30 patients, further assessment could be suggested.
RECIST criteria were considered for the evaluation of response. Kaplan Meier survival curves were generated based on the PFS and OS data and analyzed by the log rank statistic. Results Patient Characteristics Thirty patients were enrolled between May 2005 and February 2009. The median age was 67.0 years, there were 17 females and 14 males. All patients completed the first two cycles of therapy and were, therefore, assessable for toxicity and for efficacy. ECOG performance status was 0 in 24 of patients and 1 in the other 7. Peptide synthesis seven patients needed biliary drainage. The distribution of primary cancer was: gallbladder in 13 patients, ampulla of Vater in 2 patients, intrahepatic cholangiocarcinoma in 9 patients and extrahepatic bile duct in 7 patients. A total of 221 cycles were administered, the median number of cycles for a patient was 7.0. The median follow up was 22.3 months. As shown in table 1, the majority of patients had stage IV disease and the most commonly affected metastatic sites were liver and abdominal lymph nodes.At the moment, there is no standard chemotherapy regimen for advanced biliary cancer. Historically, chemotherapy had little impact on the natural history of this disease. There are several reasons for this: a lack of active agents Sodium Channel, the overall morbidity of treatment and conse quently reduced dose intensity, and the grouping together of different cancer types with different biologies.
Older chemotherapy combinations with 5 fluorouracil have demonstrated response rates of less than 15%. To our knowledge, only one published randomized study has shown an improvement in quality of life for biliary cancer patients treated with 5 fluorouracil based chemotherapy versus best supportive care, although no difference in OS was observed. In table 4, the principal phase II studies are summarized treatment, where regimens containing new agents such as gemcitabine, capecitabine, and oxaliplatin have demonstrated objective responses in 20 45% of patients and a median survival of 8 14 months. The recent approval of numerous targeted agents in a variety of solid tumors and hematologic malignancies has clearly demonstrated the clinical efficacy of such agents. How ever, the overall modest activity of these agents in,orphan, tumors such as BTC emphasizes the need for novel and more effective medical treatment options such as combinations.