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However, when screening data from these subjects were available for a given mea

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However, when screening data from these subjects were available for a given mea

Сообщение  wangqian в Вт Май 13, 2014 3:02 pm

Subjects con tinued on treatment until there was disease progression, unacceptable toxicity, or the subject withdrew consent. The trial employed an accelerated titration ABT-888 Veliparib design starting at a dose of 0. 33 mg m2, Routine antiemetic prophylaxis was administered to patients receiving a dose of 7. 11 mg m2 and above, due to nausea and vomiting observed at lower dose levels. Antiemetic prophylaxis consisted of a serotonin receptor antagonist, with or without dexamethasone, administered prior to treatment with dinaciclib, and modifications were permitted as clinic ally indicated. Toxicity, safety, and tolerability assessments To determine the MAD of dinaciclib administered as a 2 hour IV infusion, an accelerated titration design was used, whereby at least one subject was treated at each dose level starting with 0.<br><br> 33 mg m2, the dose was dou bled in sequential subjects until a DLT was observed or a subject experienced grade 2 toxicity, In the case of an observed grade 2 toxicity, a second subject was enrolled at the same dose level. If the second subject also experienced a grade 2 toxicity, 2 additional subjects were accrued at that dose level for a total of 4 subjects. AEB071 ic50 In the case of an observed DLT, additional subjects were added to the cohort until either a second subject experi enced a DLT or 6 subjects were treated at that dose level. If 2 or more subjects experienced a DLT at a given dose, then 3 additional subjects were treated at the previous lower dose, unless 6 subjects had already been treated at that dose. Dose escalations beyond the 1.<br><br> 32 mg m2 dose AG-1478 Tyrphostin AG-1478 level were administered in increments of 40% in cohorts of 3 subjects. Each subject was allocated to only a single dose level of drug. Dose delay or modification was permitted based on laboratory and clinical assess ment performed on the day of treatment. The RP2D was defined as the highest dose studied, without growth factor support, for which the incidence of DLT was less than 33%, determined based on myeloma and NSCLC mouse xenograft models, which showed complete tumor regres sion at a dose 33% of the MAD. Dose limiting toxicities were determined during the first cycle for each dose level. A DLT was defined as any grade 3 or 4 hematologic toxicity lasting for at least 1 week, or as any grade 3 or 4 nonhematologic toxicity.<br><br> Untreated nausea and vomiting, fatigue, anorexia, anemia, alope cia, or local reactions were not included in the determin ation of DLTs and did not alter the escalation schedule, unless inclusion was deemed necessary by the investigator and sponsor. Normal alkaline phosphatase level at screening that rose to greater than or equal to grade 3, grade 1 or 2 alkaline phosphatase level at screening that rose to grade 4, grade 1 or 2 aspartate aminotransferase and or alanine aminotransferase levels at screening that doubled from baseline to become greater than or equal to grade 3, and any other abnormal nonhematology laboratory value greater than or equal to grade 3 that required medical intervention to treat, led to hospitalization, or persisted for at least 1 week were also considered DLTs.


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