Multivariate analysis showed that GOLPH3 appeared to be an independent prognos

Treatment was administered to 48 subjects; 3 subjects were enrolled but did not meet protocol eligibility プロテイン キナーゼ 阻害剤 criteria and were never treated, and one subject who was enrolled did not receive any treatment because of an AE. However, when screening data from these subjects were available for a given measurement, these subjects were included in the corresponding analysis. According to the trial design, all subjects continued treatment until disease progression or treatment discontinuation due to toxicity or at the subjects request; most trial discontinuations were due to disease progression and symp tomatic deterioration, Table 1 summarizes subject demographics and baseline disease characteristics. The majority of patients enrolled in the study were white, male, and younger than 65 years old, with a mean age of 61.<br><br> 6 years. Most subjects had colorectal cancer, followed by non Lenalidomide 溶解度 small cell lung cancer, ovarian cancer, breast cancer, and melanoma, The study population had received a median of 3 chemotherapy regimens prior to enrolling into the trial. Toxicity, safety, and tolerability of dinaciclib A total of 11 subjects were administered doses of dinaciclib ranging from 0. 33 to 2. 59 mg m2; there were 2 instances of grade 2 toxicity at 1. 32 mg m2, but no DLTs were experi enced at any of these dose levels. Therefore, subsequent doses were escalated in 40% increments from 1. 85 mg m2 up to the MAD that was reached at a dinaciclib dose of 14 mg m2.<br><br> Two subjects among the 5 treated at the MAD experienced a DLT, one with orthostatic hypotension and one with elevated uric acid, A lower dose of 12 mg m2 was tested and was determined to be the RP2D for dinaciclib administered as a 2 hour IV infusion once a week for 3 weeks followed by a 1 week recovery period. A total of 11 subjects were tested at the RP2D dose; purchase LY2603618 one subject experienced septic shock as a DLT. Additional DLTs experienced with dinaciclib included hypokalemia, hypocalcemia, and hypophosphatemia expe rienced by 1 of 8 subjects treated at the 3. 63 mg m2 dose level, and deep vein thrombosis in 1 of 7 subjects treated at the 7. 11 mg m2 dose level. A total of 47 subjects reported treatment emergent adverse events, and 35 subjects experienced AEs possibly related to study drug.<br><br> The most frequently reported treatment related AEs were nausea, anemia, neutropenia, vomiting, and fatigue, At the RP2D, the most common treatment related AEs reported by at least 3 of the 11 subjects treated at this dose level were anemia, neutropenia, fa tigue, nausea, vomiting, asthenia, hyperuricemia, and pyrexia, Sixteen subjects experienced grade 3 or 4 treatment related AEs, with neutropenia and hyperuricemia being the most common. Serious AEs were reported in 17 subjects; the most common SAEs were deep vein throm bosis, sepsis, and anemia, each occurring in 3 sub jects. Not all SAEs qualified as DLTs. No discernible trend regarding tumor type and toxicity was identified, doses of approximately 5. 08 mg m2 and greater. Seven subjects were evaluable for BrdU response rate at the RP2D, and all 7 subjects were classified as responders Eleven of the 52 subjects enrolled died during this study.