Cetuximab can be safely administered once every second week at doses between 400 and 700 mg/m(2), with 500 mg/m(2) being the most convenient and feasible dose for future studies.
Background Peripheral T-cell lymphoma (PTCL) is associated with poor prognosis, particularly in patients with relapsed/refractory (R/R) disease. Pralatrexate, a folate analogue inhibitor, was the first drug approved to treat R/R PTCL. Objective As the distribution of PTCL subtypes differs between populations and few patients in the pivotal trial of pralatrexate were Asian, this study investigated the safety and efficacy of pralatrexate as monotherapy in Chinese patients with R/R PTCL. Patients and Methods In this single-arm, open-label, multicenter study, 71 patients with R/R PTCL (median [range] 2 [1–14] prior systemic treatments) were recruited from 15 centers in China and received pralatrexate IV 30 mg/m 2 /week for 6 weeks in 7-week cycles (with vitamin B 12 /folate). The primary endpoint was objective response rate (ORR) per central review (null hypothesis: ORR < 15%). Results The study’s primary objective was met: ORR (95% CI) was 52% (40–64%) ( p < 0.001) and responses were observed across pre-specified patient subgroups. Median (95% CI) duration of response was 8.7 (3.3–14.1) months and first response was observed in Cycle 1 for most (84%) patients. Median (95% CI) progression-free survival and overall survival was 4.8 (3.1–8.1) months and 18.0 (10.4–NA) months, respectively. The most common treatment-emergent adverse events were stomatitis (68% [Grade 3/4: 20%]), anemia (49% [Grade 3/4: 24%]) and alanine aminotransferase increase (41% [Grade 3/4: 4%]). Conclusions These results demonstrate that pralatrexate may represent a promising treatment option for Chinese patients with R/R PTCL. The ORR of 52% compared favorably with prior studies of pralatrexate in other populations and there were no unanticipated side effects. Trial Registration ClinicalTrials.gov identifier: NCT03349333.
ObjectiveTo assess the efficacy and safety of modified-release (MR) versus immediate-release (IR) prednisone in newly diagnosed glucocorticoid (GC)-naïve patients with polymyalgia rheumatica (PMR).MethodsPatients were randomised to double-blind MR prednisone (taken at approximately 22:00) or IR prednisone (taken in the morning), 15 mg/day for 4 weeks. The primary end point was complete response rate (≥70% reduction in PMR visual analogue scale, duration of morning stiffness and C reactive protein (CRP) (or CRP <2× upper limit of normal (ULN))) at week 4. Non-inferiority was decided if the lower 95% confidence limit (MR vs IR prednisone) was above −15%. 400 patients were planned but only 62 were enrolled due to difficulties in recruiting GC-naïve patients with PMR with CRP ≥2×ULN.ResultsThe percentage of complete responders at week 4 was numerically greater for MR prednisone (53.8%) than for IR prednisone (40.9%). Non-inferiority of MR versus IR prednisone was not proven in the primary analysis on the per protocol population (N=48; treatment difference: 12.22%; 95% CI −15.82% to 40.25%). However, sensitivity analysis on the full analysis population showed an evident trend favouring MR prednisone (N=62; treatment difference: 15.56%; 95% CI −9.16% to 40.28%). Adverse events were generally mild and transient with no unexpected safety observations.ConclusionsThe study showed a clear trend for favourable short-term efficacy of MR prednisone versus IR prednisone in early treatment of PMR. Further studies are warranted.Trial registration numberEudraCT number 2011-002353-57; Results.
to investigate the clinical relevance of peripheral blood neutrophil-lymphocyte ratio (NLR) in patients with NKTCL. Methods: Retrospective review of patients with histologically-proven NKTCL and available blood counts at diagnosis from the National Cancer Centre Singapore and Samsung Medical Center, South Korea was completed. An optimal cutoff for high NLR (>3.5) in predicting overall survival (OS) was determined using receiver operating curve analysis. Survival analysis was performed using the Kaplan-Meier method and multivariate Cox proportional models. Gene expression profiling was performed for each subgroup (n ¼ 4 per group). NLR-associated signaling pathways were explored with gene set enrichment analysis (GSEA) using the MSigDB Hallmark gene set. Results: The median age at diagnosis was 54 years (range, 17-86), with a male preponderance (70.8%). Median NLR was 2.6 (range, 0.7-24.5) and 59 patients (33.1%) possessed high NLR. High NLR was associated with advanced age 60 (p ¼ 0.032), ECOG score 2 (p ¼ 0.0025), elevation of lactate dehydrogenase (p ¼ 0.02) and IPI score 3-4 (p ¼ 0.014). Estimated 5-year OS was 53% in patients with low NLR and 25% in those with high NLR. In multivariate analysis, high NLR, in addition to B-symptoms and advanced stage, were independently associated with both worse overall survival (HR 2.08; 95% CI 1.36 to 3.18; p ¼ 0.0008) and progression-free survival (HR 1.66; 95% CI 1.11 to 2.46; p ¼ 0.0128). In subgroup analysis, the prognostic ability of NLR on OS was observed in both Singapore an (p ¼ 0.0072) and Korean (p ¼ 0.031) cohorts. GSEA suggests that high NLR is associated with tumors harboring upregulated DNA repair genes including POLD3 and ERCC2 (false discovery rate, 0.137; p < 0.001). Conclusions: High NLR is correlated with distinct tumor transcriptomic profiles in NKTCL and is an independent marker of poor survival outcomes. Legal entity responsible for the study: SGH IRB.
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