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BackgroundNeratinib is an irreversible pan-HER tyrosine kinase inhibitor approved for HER2-positive early-stage and metastatic breast cancer. Diarrhea is the most frequent side effect and the most common reason for early discontinuation. The phase II CONTROL trial investigated antidiarrheal prophylaxis or neratinib dose escalation (DE) for prevention of diarrhea. We present complete study results including final data for two DE strategies.MethodsPatients who completed trastuzumab-based adjuvant therapy received neratinib 240 mg/day for 1 year. Early cohorts investigated mandatory prophylaxis with loperamide, then additional budesonide or colestipol. Final cohorts assessed neratinib DE over the first 2 (DE1) or 4 weeks (DE2). The primary endpoint was incidence of grade ≥3 diarrhea. Health-related quality of life (HRQoL) was assessed using FACT-B and EQ-5D-5L.Results563 patients were enrolled into six cohorts. All strategies reduced grade ≥3 diarrhea with the lowest incidence in DE1 (DE1 13%; colestipol + loperamide [CL] 21%, DE2 27%; budesonide + loperamide [BL] 28%; loperamide [L] 31%; colestipol + loperamide as needed [CL-PRN] 33%). Diarrhea-related discontinuations occurred early and were lowest in DE1 (DE1 3%; CL 4%; DE2 6%; CL-PRN 8%; BL 11%; L 20%). More patients stayed on neratinib for the prescribed period versus historical controls. Prior pertuzumab use did not affect rates of grade ≥3 diarrhea, diarrhea-related discontinuations, or treatment duration. Early transient reductions in HRQoL scores were observed.ConclusionsThese complete results from CONTROL show improved neratinib tolerability with proactive management at the start of therapy. Two-week neratinib DE with loperamide as needed was particularly effective.ClinicaltrialsGov registration numberNCT02400476.

Vitamin D is important to normal bone and cartilage metabolism. Insufficient concentrations of vitamin D adversely affect calcium metabolism, osteoblastic activity, matrix ossification, bone density, and articular cartilage turnover. Osteoarthritis (OA) is a degenerative joint disease involving the cartilage and many of its surrounding tissues. In addition to damage and loss of articular cartilage, there is remodelling of subarticular bone, osteophyte formation, ligamentous laxity, weakening of periarticular muscles, and, in some cases, synovial inflammation. Pain is the major clinical symptom in knee OA joint. Objective: To estimate a relation between Vit.D deficiency and the severity of knee osteoarthritis. Patients and Methods: This study was a cross sectional study conducted on ninety (90) patients diagnosed (aged 40-55 years old) with knee osteoarthritis according to according to American college of rheumatology (ARC) criteria 2016 for diagnosis of OA. Patients were recruited from the Rheumatology Outpatient Clinic and Internal Medicine and Rheumatology Department at Ain Shams University Hospitals. Results: Our studied cases show that VAS pain score ranges from 3–7 with a mean 4.70 6 0.93 and median 4. As regard pain domini of WOMAC, it had significant relation with Vit D significant (p value ¼ 0.007) while VAS Pain Score not significant related to Vit D (p value ¼ 0.121). In current study, the correlation between stiffness and Vit D is statistically significant (p value ¼0.001), the correlation between physical function and Vit D is statistically significant (p value ¼ 0.001), the correlation between WOMAC score and Vit D was statistically significant (p value ¼ 0.001) As regard relation between Vit. D and X-Ray Kellgran-Lawrence system, it was significant in grade 1and grade 3. But it was non-significant n grade 2 &4. Conclusion: This study has demonstrated a significant association between knee OA and vitamin D deficiency and corresponding with the development of knee cartilage damage. As Low levels of vitamin D may not play a critical role in OA pathogenesis and progression [ABSTRACT FROM AUTHOR]