182 research outputs found

    Malignant Lymphoma

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    Phase 1 study of the investigational Aurora A kinase inhibitor alisertib (MLN8237) in East Asian cancer patients: pharmacokinetics and recommended phase 2 dose

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    Purpose This phase 1 study assessed the pharmacokinetics (PK), maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), safety, and preliminary efficacy of the investigational Aurora A kinase inhibitor, alisertib, in East Asian patients with advanced solid tumors or lymphomas. Patients and Methods Patients received alisertib twice-daily (BID) for 7 days in 21-day cycles. Doses were escalated (3 + 3) from 30 mg BID based on cycle 1 dose-limiting toxicities (DLTs) until the MTD, followed by expansion for PK/safety characterization. Results Thirty-six patients (61 % Chinese, 36 % Korean, 3 % Malay) received alisertib (30 mg BID, n = 30; 40 mg BID, n = 6; median, 2.5 cycles). Alisertib exposures increased approximately dose proportionally, and mean half-life was 16 h. Geometric mean apparent oral clearance (2.65 L/h) was 40 % lower than previous estimates in Western patients, resulting in approximately 70 % higher mean dose-normalized, steady-state exposures (735 nM*h/mg) in East Asian patients. Two patients experienced DLTs at 40 mg BID (grade 3 stomatitis; grade 4 neutropenia); the MTD/RP2D was 30 mg BID. Common toxicities (grade a parts per thousand yen3 at RP2D) were neutropenia (50 %), diarrhea (13 %), and stomatitis (10 %). One patient with extranodal T-/NK-cell lymphoma (nasal type) achieved a partial response and 18 (51 %) had stable disease. Conclusion The MTD/RP2D of alisertib in East Asian patients (30 mg BID) was lower than in Western patients (50 mg BID), consistent with higher systemic exposures in the East Asian population. Alisertib was generally well tolerated and showed signs of antitumor activity in East Asian cancer patients

    Pathogenesis and biomarkers of natural killer T cell lymphoma (NKTL)

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    Abstract Natural killer T cell lymphoma (NKTL) is an aggressive disease with very poor treatment outcomes in the advanced stages. With chemotherapy, initial response rates to treatment are high but responses are short lived. A better understanding of the complex molecular pathogenesis of this disease is essential in order to design and develop better therapeutics with improved efficacy. This review aims to summarise the key pathogenic mechanisms in NKTL which may have significant prognostic and therapeutic implications

    Breakthrough Febrile Neutropenia and Associated Complications in Non-Hodgkin’s Lymphoma Patients Receiving Pegfilgrastim

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    &lt;i&gt;Background:&lt;/i&gt; Febrile neutropenia (FN) is a dose-limiting complication of chemotherapy. Judicious usage of prophylactic granulocyte-colony-stimulating factors, such as pegfilgrastim, can prevent the occurrence of FN. Although studies have been conducted to evaluate the effectiveness of pegfilgrastim to prevent FN in lymphoma patients receiving myelosuppressive chemotherapy, limited data is available to identify patients who are at risk of developing FN despite primary prophylaxis with pegfilgrastim (breakthrough FN). &lt;i&gt;Objectives:&lt;/i&gt; The aim of this study is to: (1) identify clinical characteristics of patients who develop breakthrough FN, and (2) provide descriptive data on the incidence of breakthrough FN among lymphoma patients. &lt;i&gt;Methods:&lt;/i&gt; This is a single-centre, retrospective cohort study. Non-Hodgkin’s lymphoma patients who received CHOP-based chemotherapy with pegfilgrastim between January 2007 and May 2009 were identified through the Singapore Lymphoma Registry. Patient demographics, past and present medical history, cancer treatment history and laboratory parameters were collected from electronic databases and medical records. In this study, patients did not receive oral antibiotic prophylaxis along with chemotherapy. &lt;i&gt;Results:&lt;/i&gt; A total of 132 patients were included in the final analysis. Median age of patients was 55 years. The incidence of breakthrough FN among patients in cycle 1 and across all cycles was 4.5% and 13.6%, respectively (n = 132). 3.3% (n = 60) of the patients receiving dose-dense chemotherapy had breakthrough FN, and this was 22.2% (n = 72) in patients receiving standard dose chemotherapy. Administration of chemotherapy every 21 days (adjusted OR = 12.1, p = 0.009) and patients with positive blood cultures (adjusted OR = 18.1, p = 0.001) were strongly associated with the occurrence of breakthrough FN. &lt;i&gt;Conclusion:&lt;/i&gt; Despite routine administration of pegfilgrastim with CHOP chemotherapy, a high proportion of patients experienced FN after chemotherapy. Identifying patients at risk for breakthrough FN events may allow the optimization of myeloid growth factor usage among lymphoma patients receiving chemotherapy.</jats:p
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