Patient eligibility Patients aged 18 years or older with histologically confirmed MDS fitting any of the World Health Organization SB 216763 classifications were eligible for this study. Patients with <5% bone marrow blasts also had to meet one of the following criteria: symptomatic anemia with a hemoglobin <10.0 g/dl or requiring red blood cell transfusions in the 3 months before study entry, thrombocytopenia with two or more platelet counts <50,000/μl or a significant hemorrhage requiring platelet transfusions, or neutropenia with two or more absolute neutrophil counts <1,000/μl. Additional inclusion criteria were: ≤2 prior therapies for MDS, ineligibility for allogeneic stem cell transplant, no prior therapy for MDS with a HDAC inhibitor, Eastern Cooperative Oncology Group performance status of 02, adequate renal and hepatic function, and life expectancy greater than 12 weeks.
Patients were excluded if they had a marked baseline prolongation of QT/QTc interval and/or significant cardiovascular disease. Cytogenetic risk was assigned based on the criteria of the International Prognostic Scoring System . Nelarabine molecular weight The study protocol was approved by the Human Research Protection Office at participating institutions. All patients provided written informed consent. Study treatment This was on open label, single arm, multicenter phase II study of belinostat administered as 1,000 mg/m2 IV over 30 min on days 15 of a 21 day cycle. Growth factors were not routinely administered. Premedication with an antiemetic was recommended. A 25% dose reduction was allowed for patients who developed treatment related toxicity, including worsening cytopenia.
Patients continued to receive belinostat for eight cycles or until one of the following events occurred: disease progression, intercurrent illness preventing further treatment, unacceptable adverse event, or patient decision to withdraw from the study. Responding patients could continue the study treatment beyond eight cycles, until one cox1 inhibitor of the above criteria applied. Gefitinib ic50 Patients were evaluated by complete blood count performed weekly during cycle 1 and then at the beginning of each cycle. Bone marrow biopsy and aspiration were performed after every two cycles. Response criteria followed the definitions of the international working group . Toxicities were graded per NCI CTC AE Version 3.0.
Statistical analysis The primary endpoint was the proportion of evaluable patients achieving a confirmed response during the first 12 weeks of treatment. Secondary endpoints included time to progression, overall survival, duration of response, time to discontinuation of treatment, and toxicity. The study had 90% power to detect an effective treatment if the true proportion carbohydrates of patients who achieve a confirmed response rate is at least 25% versus the null hypothesis that the true confirmed response rate is at most 10%, using a two stage Simon design with an α level of 0.10. Fifty patients were required, with 21 enrolled and assessed in the first stage. If two or fewer success were observed in stage I, accrual could be terminated. Results Patient characteristics and treatment Twenty one patients were accrued, and all were eligible and evaluable . Patients were median 13.4 months from diagnosis, and at the time of study entry.