Cutaneous T-cell lymphomas (CTCL) are a group of non-Hodgkin lymphomas that typically present in the skin but can progress to systemic involvement. The optimal treatment for patients who relapse from or are refractory to systemic chemotherapy remains unclear. Romidepsin is a potent, class-I selective histone deacetylase inhibitor approved for the treatment of patients with CTCL who have had ≥1 prior systemic therapy. Here, we present a subanalysis of two phase-2 trials (NCT00106431, NCT00007345) of romidepsin in patients with CTCL who had prior treatment with systemic chemotherapy. Patients with prior chemotherapy were able to achieve durable responses to romidepsin, and response rates were similar to those in patients who were chemotherapy naïve. Overall, no new safety signals emerged in patients who had received prior chemotherapy. The data presented here suggest that romidepsin is safe and effective in patients with CTCL who received prior systemic chemotherapy.

Purpose: The goal of this study was to evaluate the safety and tolerability of dalfampridine extended release (D-ER) in a pilot study of adults with cerebral palsy (CP) and limited ambulatory ability, and to explore drug effects on sensorimotor function.Methods: An initial double-blind, single-dose crossover study was performed in 11 individuals randomized 1:1 to receive D-ER (10 mg) or placebo, followed by a 2 day washout period and the opposite treatment, with evaluation for safety and tolerability. A twice daily dosing, double-blind, placebo-controlled, crossover study was then performed. Participants were randomized in a 1:1 ratio to 1 of 2 sequences: 1 week of D-ER (10 mg BID) or placebo, followed by a 1-week washout and 1 week of the opposite treatment. Key inclusion criteria were age 18 to 70 years, body mass index 18.0 to 30.0 kg/m(2), diagnosis of CP, and ability to perform all study procedures. Key exclusion criteria were severe CP, moderate or severe renal impairment, history of nonfebrile seizures, and prior dalfampridine use. Primary outcomes were safety profile and tolerability. Exploratory functional outcomes comprised changes in upper and lower extremity sensorimotor function (grip and pinch strength tests), manual dexterity (Box and Block Tests), and walking speed (Timed 25-Foot Walk). The most pronounced measured functional deficit in each individual was defined as the exploratory primary functional end point. Full crossover data were analyzed by using a mixed effects model.Findings: Among the 24 total participants who were randomized to treatment and completed the twice daily dosing phase study, their mean age was 38.6 years (range, 20-62 years), 54% were women, and 83% had spastic CP. Adverse events were consistent with previous D-ER trials, most commonly headache (13% D-ER, 4% placebo), fatigue (13% D-ER, 0% placebo), insomnia (8% D-ER, 4% placebo), diarrhea (4% D-ER, 4% placebo), and nausea (4% D-ER, 4% placebo). The mixed model analysis of full crossover data identified no significant difference between D-ER and placebo in the primary functional analysis (the most pronounced deficit; P = 0.70) or in the secondary analyses (hand strength [P = 0.48], manual dexterity [P = 0.13], or walking speed [P = 0.42]). (C) 2017 The Authors. Published by Elsevier HS Journals, Inc.

Patients with cutaneous T-cell lymphoma (CTCL) who have cutaneous tumors or folliculotropic disease involvement typically have a poor prognosis. Analysis of the pivotal phase II trial of romidepsin for relapsed or refractory CTCL showed that single-agent romidepsin induced a clinical response or stable disease in most patients with cutaneous tumors and/or folliculotropic disease involvement, supporting its use in these patient populations.Background: Tumor stage and folliculotropic mycosis fungoides are uncommon subtypes of cutaneous T-cell lymphoma (CTCL) with an aggressive disease course. Romidepsin is a histone deacetylase inhibitor approved by the US Food and Drug Administration for patients with CTCL who have received >= 1 previous systemic therapy. In the present study, we examined the efficacy and safety of romidepsin in patients from the pivotal, single-arm, open-label, phase II study of relapsed or refractory CTCL with cutaneous tumors and/or folliculotropic disease involvement. Materials and Methods: Patients with CTCL who had received >= 1 previous systemic therapy received romidepsin at 14 mg/m(2) on days 1, 8, and 15 of 28-day cycles. Responses were determined by a composite endpoint (assessments of the skin, blood, and lymph nodes). Patients with cutaneous tumors and/or folliculotropic disease involvement were identified by review of diagnosis and histology reports. Results: The objective response rate to romidepsin was 45% in patients with cutaneous tumors (n = 20) and 60% in patients with folliculotropic disease involvement (n = 10). Conclusion: Romidepsin is active in subtypes of CTCL with less favorable outcomes, such as tumor stage and folliculotropic mycosis fungoides. (C) 2016 Elsevier Inc.

Cutaneous T-cell lymphoma (CTCL) is a rare heterogeneous group of non-Hodgkin lymphomas that arises in the skin but can progress to systemic disease (lymph nodes, blood, viscera). Historically, in clinical trials of CTCL there has been little consistency in how responses were defined in each disease “compartment”; some studies only assessed responses in the skin. The histone deacetylase inhibitor romidepsin is approved by the US Food and Drug Administration for the treatment of CTCL in patients who have received at least one prior systemic therapy. Phase II studies that led to approval used rigorous composite end points that incorporated disease assessments in all compartments. The objective of this analysis was to thoroughly examine the activity of romidepsin within each disease compartment in patients with CTCL. Romidepsin was shown to have clinical activity across disease compartments and is suitable for use in patients with CTCL having skin involvement only, erythroderma, lymphadenopathy and/or blood involvement.

A previous interim report of MM-011, the first study that combined lenalidomide with anthracycline-based chemotherapy followed by lenalidomide maintenance for relapsed and/or refractory multiple myeloma (RRMM), showed promising safety and activity. We report the long-term outcomes of all 76 treated patients with follow-up ≥ 5 years. This single-center phase I/II study administered lenalidomide (10 mg on days 1-21 of every 28-day cycle), intravenous liposomal doxorubicin (40 mg/m(2) on day 1), dexamethasone (40 mg on days 1-4), and intravenous vincristine (2 mg on day 1). After 4-6 planned induction cycles, lenalidomide maintenance therapy was given at the last tolerated dose until progression, with or without 50 mg prednisone every other day. The median number of previous therapies was 3 (range, 1-7); 49 (64.5%) patients had refractory disease. Forty-three (56.6%) patients received maintenance therapy. Grade 3/4 adverse events occurred during induction and maintenance therapy in 48.7% and 25.6% of patients, respectively. Four (5.3%) treatment-related deaths occurred during induction. Responses were seen in 53.0% (at least partial response) and 71.2% (at least minor response) of patients. Overall, median progression-free survival and overall survival were 10.5 and 19.0 months, respectively; in patients with refractory disease these values were 7.5 and 11.3 months, respectively. Lenalidomide with anthracycline-based chemotherapy followed by maintenance lenalidomide provided durable control in patients with RRMM (ClinicalTrials.gov number, NCT00091624).

Background: CTCL is a primarily indolent, heterogeneous group of non-Hodgkin lymphomas that arise in the skin but can progress to systemic disease (blood, lymph nodes, viscera). For patients who require systemic treatment, nonchemotherapeutic agents are currently preferred, and multiagent chemotherapies are typically reserved for patients with disease that is particularly aggressive or relapsed/refractory to multiple prior systemic therapies. Durable clinical responses are difficult to achieve, and selection of the best treatment following chemotherapy is unclear. Romidepsin is a potent, bicyclic class 1 selective HDAC inhibitor approved by the US Food Drug Administration for treatment of patients with CTCL who had received ≥ 1 prior systemic therapy as well as patients with peripheral T-cell lymphoma who have received ≥ 1 prior therapy. In the pivotal phase 2 study for the treatment of relapsed/refractory CTCL (GPI-04-0001), romidepsin resulted in rapid and durable responses, with an objective response rate (ORR) of 34% (33/96), including 6% (6/96) with complete response (CR), and median duration of response (DOR) of 15 months. Reduction in pruritus (a common and often debilitating symptom of CTCL) with romidepsin treatment was seen in both clinical responders and nonresponders. Here, we present data for patients with prior systemic chemotherapy from GPI-04-0001.

Patients with cutaneous T-cell lymphoma (CTCL) frequently experience severe pruritus that can significantly impact their quality of life. Romidepsin is approved by the US Food and Drug Administration (FDA) for the treatment of patients with CTCL who have received at least one prior systemic therapy, with a reported objective response rate of 34%. In a phase 2 study of romidepsin in patients with CTCL (GPI-04-0001), clinically meaningful reduction in pruritus (CMRP) was evaluated as an indicator of clinical benefit by using a patient-assessed visual analog scale. To determine the effect of romidepsin alone, confounding pruritus treatments including steroids and antihistamines were prohibited. At baseline, 76% of patients reported moderate-to-severe pruritus; 43% of these patients experienced CMRP, including 11 who did not achieve an objective response. Median time to CMRP was 1.8 months, and median duration of CMRP was 5.6 months. Study results suggest that the clinical benefit of romidepsin may extend beyond objective responses.

Statistics in MedicineVolume 28, Issue 3 p. 534-536 Letter to the Editor Comments on 'Rebuttal to Carpenter et al.' Comments on 'Fixed vs random effects meta-analysis in rare event studies: The rosiglitazone link with myocardial infarction and cardiac death' by J. J. Shuster, L. S. Jones and D. A. Salmon, Statistics in Medicine 2008; 27:3912–3914 Joel Waksman, Joel Waksman Wyeth Consumer Healthcare, Madison, NJ 07940, U.S.A.Search for more papers by this authorChristine Kollar, Christine Kollar Everest Clinical Research Services Inc., Little Falls, NJ 07424, U.S.A.Search for more papers by this author Joel Waksman, Joel Waksman Wyeth Consumer Healthcare, Madison, NJ 07940, U.S.A.Search for more papers by this authorChristine Kollar, Christine Kollar Everest Clinical Research Services Inc., Little Falls, NJ 07424, U.S.A.Search for more papers by this author First published: 05 January 2009 https://doi.org/10.1002/sim.3485Citations: 3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. REFERENCES 1 Shuster JJ, Jones LS, Salmon DA. Fixed vs random effects meta-analysis in rare event studies: the rosiglitazone link with myocardial infarction and cardiac death. Statistics in Medicine 2007; 26: 4375– 4385. 2 Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. The New England Journal of Medicine 2007; 356: 2457– 2471. 3 Carpenter J, Rucker G, Schwarzer G. Comments on 'Fixed vs random effects meta-analysis in rare event studies: the rosiglitazone link with myocardial infarction and cardiac death' by J. J. Shuster, L. S. Jones and D. A. Salmon. Statistics in Medicine 2008; 27: 3910– 3912. 4 Shuster JJ, Jones LS, Salmon DA Rebuttal to Carpenter et al. Comments on 'Fixed vs random effects meta-analysis in rare event studies: the rosiglitazone link with myocardial infarction and cardiac death'. Statistics in Medicine 2008; 27: 3912– 3914. 5 Kollar C, Schneider H, Waksman J, Krusinska E. Meta-analysis of the efficacy of a single dose of phenylephrine 10 mg compared with placebo in adults with acute nasal congestion due to the common cold. Clinical Therapeutics 2007; 29: 1057– 1070. Citing Literature Volume28, Issue310 February 2009Pages 534-536 ReferencesRelatedInformation

Background: Although nonprescription oral phenylephrine 10 mg has been judged "generally recognized as safe and effective" by the US Food and Drug Administration (FDA), its efficacy as a nasal decongestant has been questioned.Objective: This study assessed available data on the efficacy, of oral phenylephrine 10 mg as a nasal decongestant.Methods: Three sources were used to identify potentially, relevant publications-the bibliography of the phenylephrine section of the 1976 FDA monograph on over-the-counter cold, cough, allergy, bronchodilator, and antiasthmatic products; a 2004 Cochrane Review of nasal decongestants for the common cold; and a search of MEDLINE from 1966 through January 2007 using the term phenylephrine nasal. To be included in the analyses, studies had to have a single-dose, randomized, placebo-controlled design; involve an orally, administered product in which phenylephrine 10 mg was the sole active ingredient; enroll patients with acute nasal congestion due to the common cold; evaluate nasal airway resistance (NAR) as the efficacy end point; and have sufficient data in the study report to allow reanalysis and/or meta-analysis of phenylephrine 10 mg versus placebo. Reanalysis of individual studies and fixed-effects and random-effects meta-analyses were performed. Statistical significance at 30 and 60 minutes after dosing (the primary time points) and a >= 20% reduction in NAR from baseline were considered indicative of a clinically meaningful difference.Results: Fit-teen potentially relevant studies were identified, of which 8 met the inclusion criteria. Data from 7 crossover studies involving a total of 113 subjects were reanalyzed and then pooled for meta-analysis; results from the initial phase of the eighth study, a parallel-group trial involving 50 subjects, were included in the reanalysis of individual studies but not in the meta-analyses. Significant differences in favor of phenylephrine were seen in 4 of the 8 studies (P <= 0.05). Phenylephrine 10 mg was significantly more effective than placebo at the primary time points and at 90 minutes after dosing in the meta-analyses using both the fixed-effects and random-effects models (P <= 0.05). At 45, 120, and 180 minutes after dosing, phenylephrine 10 mg was also significantly more effective than placebo in the fixed-effects model (P <= 0.05). Between 30 and 90 minutes after dosing, percent reductions from baseline in NAR ranged from 6.0 percentage points higher with phenylephrine than with placebo (at 30 and 45 minutes after dosing) to 16.6 percentage points higher (at 60 minutes after dosing). From 60 to 180 minutes after dosing, the percent reductions from baseline were generally >= 20% with phenylephrine.Conclusion: These meta-analyses of 7 crossover studies and the reanalysis of a parallel-group study support the effectiveness of a single oral dose of phenylephrine 10 mg as a decongestant in adults with acute nasal congestion associated with the common cold.