Effect of subcutaneous methylnaltrexone on patient-reported constipation symptoms

AbstractBackgroundMethylnaltrexone, a selective peripheral acting mu-opioid receptor antagonist, alleviates the constipating effects of opioids without affecting centrally mediated analgesia.ObjectivesTo assess the effect of subcutaneous (SC) methylnaltrexone injection on patient-reported constipation symptoms and pain scores.MethodsA total of 469 subjects on opioids for chronic non-malignant pain with opioid-induced constipation were randomized to methylnaltrexone SC with once daily (QD) or every other day (QOD) dosing or placebo for 4 weeks. Constipation symptoms and pain were assessed using the patient assessment of constipation–symptoms (PAC-SYM) questionnaire and a 11-point scale, respectively, at baseline, Day 14 and Day 28. Change from baseline in PAC-SYM and pain scores were compared between methylnaltrexone and placebo arms at Day 28 using analysis of covariance, with treatment group as factor and baseline score as covariate.ResultsA majority of patients were women (60%), average age was 49 years old, and back pain (60%) was the primary pain condition. At Day 28, the methylnaltrexone SC QD group showed a significant improvement over placebo for rectal symptoms (−0.56 vs. –0.30; P < 0.05), stool symptoms (−0.76 vs. –0.43; P < 0.001) and global scores (−0.62 vs. –0.37; P < 0.001). Improvement in stool symptoms (−0.69 vs.−0.43; P < 0.05) and the global scores (−0.52 vs. –0.37; P < 0.05) were significantly greater than placebo in the methylnaltrexone QOD group. Differences in change from baseline in abdominal symptoms and pain scores between the methylnaltrexone SC QD or QOD dosing arms and placebo were not significant.ConclusionThe results of our study indicate significant improvement in constipation symptoms with methylnaltrexone QD or QOD dosing compared to placebo without a significant effect on pain scores

Drug-Related Problems and Quality of Life in Arthritis and Low Back Pain Sufferers

AbstractObjectiveThe objective of this study was to determine the relationship between drug-related problems (DRPs) and health-related quality-of-life (HRQoL) in ambulatory, community-dwelling patients with musculoskeletal disorders.MethodsA 12-month, prospective, observational study was conducted in 12 independent community pharmacies in eastern Iowa. Ambulatory patients with self-reported diagnoses of osteoarthritis, rheumatoid arthritis, or low back pain were invited to participate. During quarterly visits to the pharmacy, patients used touch-screen computers to fill out the Short Form-36 (SF-36) general health survey. Using the results of these point-of-service health status assessments, community pharmacists interviewed patients to assess for DRPs. To examine the influences of different DRP characteristics on HRQoL and controlling for potential confounders, both univariate and multivariate analyses were performed using the change in physical component summary (PCS) score and mental component summary (MCS) score of the SF-36 from baseline to 12 months as the dependent variables. In each regression, the independent variables were those significant variables from the univariate analyses, as well as the types of DRPs and their outcomes.ResultsA total of 461 patients were enrolled in the study. Through 12 months, 926 cumulative DRPs were identified. Overall regression models were significant for the PCS and MCS scores, respectively. Two types of DRPs showed significant negative associations with change in PCS: wrong drug and needs additional drug therapy. One type of DRP showed significant negative association with change in MCS: needs additional drug therapy. Resolution or improvement in DRPs showed a significant positive correlation with change in MCS but not PCS.ConclusionsTwo DRPs, needs additional drug therapy and wrong drug, are associated with reduced self-reported physical health in arthritis and low back pain, while the DRP needs additional drug therapy is also associated with reduced self-reported mental health. Resolution of DRPs is associated with improvement in mental health in this cohort

Efficacy + safety of palbociclib (P) in patients (pts) &lt;= 50 y with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC): Subgroup analysis of 2 randomized phase 3 studies (vol 41s1, pg s11, 2018)

© 2019 Elsevier LtdTwo of the authors names appeared incorrectly in the byline. The correct names are Anil Abraham Joy and Kathy Puyana Theall.Y

Palbociclib plus endocrine therapy in older women with HR+/HER2- advanced breast cancer: A pooled analysis of randomised PALOMA clinical studies

Aim: Because incidence of breast cancer and comorbidities increase with age, it is important to determine treatment benefit in elderly patients. We evaluated outcomes with palbociclib plus endocrine therapy in patients aged >= 65 years. Methods: Data were pooled from three randomised studies (NCT00721409, NCT01740427 and NCT01942135) of women with HR+/HER2- advanced breast cancer (ABC). In PALOMA-1 (open-label) and PALOMA-2 (double-blind, placebo-controlled), treatment-naive patients received palbociclib plus letrozole or letrozole alone. In PALOMA-3 (double-blind, placebo-controlled), patients with endocrine-resistant disease received palbociclib plus fulvestrant or fulvestrant alone. Results: Among 528 patients treated with palbociclib plus letrozole and 347 treated with palbociclib plus fulvestrant, 218 (41.3%) and 86 (24.8%), respectively, were aged >= 65 years. Versus endocrine therapy alone, median progression-free survival was significantly improved in patients aged 65-74 years (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.45-0.97; P = 0.016) and >= 75 years (HR, 0.31; 95% CI, 0.16-0.61; P= 75 years received palbociclib plus fulvestrant (HR, 0.59; 95% CI, 0.19-1.8; P = 0.18). Patient-reported functioning and quality of life was maintained. No clinically relevant differences in palbociclib exposure were observed between age groups. Although myelosuppression was more common among patients aged >= 75 years, incidence of grade >= III myelosuppression was similar across age groups, and febrile neutropenia was uncommon (<= 2.4%); no new safety concerns were identified in older patients. Conclusions: Palbociclib plus endocrine therapy is an effective, well-tolerated treatment for older patients with ABC. (C) 2018 Published by Elsevier Ltd

Palbociclib plus letrozole as first-line therapy in postmenopausal Asian women with metastatic breast cancer: Results from the phase III, randomized PALOMA-2 study

PURPOSE In PALOMA-2, palbociclib plus letrozole significantly improved progression-free survival (PFS) as initial treatment of estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer. We assessed the benefit of palbociclib plus letrozole in Asians. PATIENTS AND METHODS Of 666 enrolled postmenopausal women with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer (no prior treatment of advanced disease), 95 were Asian. Patients were randomly assigned 2:1 to receive palbociclib plus letrozole or placebo plus letrozole. The primary end point was investigator-assessed PFS. Secondary end points were overall survival, objective response, patient-reported outcomes, pharmacokinetics, and safety. RESULTS Median PFS was significantly longer in Asian patients who received palbociclib plus letrozole versus placebo plus letrozole (25.7 months [95% CI, 19.2 months to not estimable] v 13.9 months [95% CI, 7.4 to 22.0 months]; hazard ratio, 0.49; 95% CI, 0.27 to 0.87; P= .007). The most common toxicities with palbociclib were hematologic and more frequent among Asians versus non-Asians: neutropenia (any grade, 95.4% v 76.8%; grade 3/4, 89.2% v 62.5%), leukopenia (43.1% v 38.3%; 32.3% v 23.5%), and thrombocytopenia (27.7% v13.5%; 4.6% v 1.1%). No Asians had febrile neutropenia. Discontinuation rates as a result of adverse events were similar among Asian and non-Asian patients who received palbociclib plus letrozole (10.8% and 9.5%). In Asians, quality of life (QOL) was maintained with no significant differences observed between treatments from baseline in breast cancer-specific QOL and general health status scores. Change from baseline in EuroQol five dimensions index scores was significantly higher with palbociclib plus letrozole (0.013 v-0.069; P= .0132). Geometric mean palbociclib trough concentration values were higher in Asians versus non-Asians (93.8 v 61.7 ng/mL). CONCLUSION Consistent with the overall study population, the addition of palbociclib to letrozole significantly improved PFS in Asians. Hematologic toxicities were more frequent in Asians versus non-Asians but manageable with early dose modifications while maintaining QOL. (C) 2019 by American Society of Clinical Oncolog

First-line crizotinib versus chemotherapy in ALK-positive lung cancer.

The efficacy of the ALK inhibitor crizotinib as compared with standard chemotherapy as first-line treatment for advanced ALK-positive non-small-cell lung cancer (NSCLC) is unknown