thrombocytopenia, or anemia grade C2 developed, the use of recombinant human granulocyte colony stimulating factor, thrombopoietin or interleukin 11, or erythropoietin was permitted. Prophylactic administrations Cyclophosphamide of G CSF were not performed. Dose modification Treatment interruption or dose adjustments were made on the basis of hematologic and nonhematologic toxicities. Treatment was interrupted in cases of grade 2 or higher toxicities and was not resumed until the adverse event was improved to grades 1 or 0. In case of grade 0 2 toxicity, chemotherapy was not adjusted for the next cycle, but in grade 3 toxicity a 25% dose reduction of both gemcitabine and vinorelbine was instituted for the next cycle.
In case of grade 4 hematologic toxicity, a 50% dose reduction of both drugs were applied, while the patient was out of study in case of any grade 4 nonhaematological toxicity. Statistical analysis PI3K AKT Signaling Pathways The primary end point of the study was to determine the response rate and toxicity. The secondary end points included PFS, OS, and prognostic factors associated with disease control, PFS, and OS. The required number of patients for this study was calculated according to Simon optimal two stage designs, with predetermined 0.05, power 1 0.80. The null hypothesis was that the response rate was 20% versus the alternative that it was at least 40%, and then 13 patients were to be enrolled during the first step and an additional 30 patients during the second step. If three or less responses occurred among the first 13 patients or 12 or less responses in the total population of 43 patients, the treatment had to be judged ineffective and the study had to be terminated.
Assuming a dropout rate of 15%, a total of 51 patients were SRC Signaling Pathway to be enrolled. PFS was measured from the date therapy was initiated to the date of documented disease progression or death. OS was measured from the date therapy was initiated to the date of death or final follow up. PFS and OS were calculated via the Kaplan Meier method. Pearson,s v2 test was used to investigate the influence of baseline characteristics on disease control, unless a group contained five individuals or less, when Fisher,s exact test was used. The baseline characteristics included into the analysis were age, ECOG performance status, estrogen receptor status, progestin receptor status, human epidermal growth factor receptor 2, associated chronic diseases, visceral metastasis, number of metastatic locations, and treatment line.
Baseline characteristics and tumor response were analyzed for PFS and OS by Log rank test. Cox proportional hazards multivariate modeling was used to identify factors that independently predicted PFS and OS. All data were analyzed by SPSS for windows version 16.0. Results Patients, characteristics Fifty one patients were enrolled between January 2005 and December 2009 in Shandong Erlotinib 183319-69-9 Tumor Hospital and Institute. The study was not suspended for interim evaluation because four responses had been documented by the end of the first stage of accrual. Table 1 provides baseline demographic data. Median institutionalized patient age was 73 years. The main metastatic locations were lymph nodes, lung, and bone. Twentyeight patients received gemcitabine plus vinorelbine in the first line setting.