Our results support the clinical testing of combina tions of PI3K inhibition wi

There was one reported death during the course of the trial, which was considered unrelated to treatment with MK 2206 in combination with trastuzumab. No clear patterns or apparent differences in adverse experi ences were observed between the 60 mg QOD and 135 mg QW cohorts. Clinical ARQ 197 availability response Among the evaluable patients who were treated with study medications for at least one cycle, one patient achieved complete response, one patient had partial response, and five patients had stable disease for 4 months or longer. Based on data collected by the time of discontinuation of the study, the clinical benefit response rate was determined to be 24%, and the median time to progression was 72 days. One patient, who continued treatment after database lock, received 18 cycles of ther apy before discontinuing due to skin rash.<br><br> Details of patients who responded to treat ment are presented in Table 3, all patients who achieved CR and PR had breast cancer, and a single AZD0530 ic50 male patient with gastric cancer achieved SD as a best response. The patient with gastric cancer had not received trastuzumab in the past, while all the other patients with breast can cer had progressed on trastuzumab with an interval from the last dose of trastuzumab of 0 to 68 days. The one patient with CR had metastatic breast cancer with progressive chest wall lesions while on trastuzumab, dur ing the course of our study, the metastatic skin lesions completely resolved after two cycles of treatment. Unfor tunately, this patient elected to stop receiving treatment due to a flare up of ulcerative colitis during cycle 6 of treatment.<br><br> The time to pro gression for all enrolled patients and the best target lesion response are depicted in Figure 2. AMN-107 641571-10-0 Pharmacokinetics Mean plasma concentrations of MK 2206 administered as 45 mg or 60 mg QOD doses and as 135 mg or 200 mg QW doses with a standard dose regimen of trastuzu mab are shown in Figure 3. MK 2206 was absorbed, with median time to maximum concentration ranging from 4 to 6 hours after co administration of 45 mg or 60 mg QOD doses of MK 2206 with trastuzumab, and 4 to 8 hours after 135 mg and 200 mg QW doses of MK 2206 with trastuzumab. Interindividual variability of plasma concentrations were moderate to high, a small number of patients received a 45 mg MK 2206 QOD dose, only two patients completed dosing of 200 mg MK 2206 QW and pharmacokinetic sampling in cycle 1 as scheduled.<br><br> The mean accumulation ratio of Cmax and AUC0 to 48 hours after multiple doses over 21 to 24 days, expressed as the geometric mean ratio last dose first dose, ranged from 2. 34 to 2. 76 for the 45 mg and 60 mg QOD doses. The effective half life determined from Cmax and AUC accumulations ratio ranged from 60 to 96 hours, consistent with the mean terminal half life of 63 to 89 hours for MK 2206 alone, and suggests that elimination of MK 2206 was not altered after co administration with trastuzumab. The geometric mean ratios of Cmax after multiple dosing for 21 to 22 days for patients on the 135 mg and 200 mg MK 2206 QW dosing schedule were 1. 26 and 1. 30, respectively. The effective half life based on accumula tion ratio of Cmax and AUC was 74 to 79 hours.