NEPA efficacy and tolerability during (neo)adjuvant breast cancer chemotherapy with cyclophosphamide and doxorubicin.

OBJECTIVES: This is a prospective study evaluating NEPA in patients with breast cancer (the NEPA group), who received (neo)adjuvant AC chemotherapy (consisting of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2). The primary objectives were to assess the efficacy and safety of NEPA in controlling chemotherapy-induced nausea and vomiting (CINV). The secondary objectives were to compare CINV between the NEPA group and historical controls (the APR group) who received aprepitant in an earlier prospective randomised study. PATIENTS AND METHODS: 60 patients participated in the NEPA group; 62 were in the APR group. Eligibility criteria of both groups were similar, that is, Chinese patients with breast cancer who were treated with (neo)adjuvant AC. NEPA group received NEPA and dexamethasone; APR group received aprepitant, ondansetron and dexamethasone. Individuals filled in self-reported diary, visual analogue scale for nausea and Functional Living Index-Emesis questionnaire. RESULTS: Within the NEPA group, 70.0%, 85.7% and 60.0%, respectively reported complete response in the acute, delayed and overall phases in cycle 1 AC. When compared with the historical APR group during cycle 1 AC, NEPA group achieved significantly higher rates of complete response, complete protection, total control, 'no significant nausea' and 'no nausea' in the delayed phase; similar findings were noted in the overall phase with significantly better quality of life. Superior efficacy of NEPA was maintained over multiple cycles. Both antiemetic regimens were well tolerated. CONCLUSION: In this study on Chinese patients with breast cancer who were uniformly receiving AC, NEPA was effective in controlling CINV. TRIAL REGISTRATION NUMBER: NCT03386617.

A randomized study of olanzapine-containing versus standard antiemetic regimens for the prevention of chemotherapy-induced nausea and vomiting in Chinese breast cancer patients.

OBJECTIVES: Chemotherapy-induced nausea and vomiting (CINV) are distressing symptoms. This randomized study evaluated the antiemetic efficacies of standard antiemetic regimen with/without olanzapine. PATIENTS AND METHODS: Eligible patients were chemotherapy-naive Chinese breast cancer patients who were planned for (neo)adjuvant doxorubicin/cyclophosphamide. Antiemetic regimen for all studied population included aprepitant, ondansetron and dexamethasone; patients were randomized to Olanzapine (with olanzapine) or Standard arms (without olanzapine). Patients filled in self-reported diaries and completed visual analogue scales for nausea, as well as Functional Living Index-Emesis questionnaires. Blood profiles including fasting glucose and lipids were monitored. RESULTS: 120 patients were randomized. In Cycle 1 doxorubicin/cyclophosphamide, the Olanzapine arm had significantly higher rates of "Complete Response" than the Standard arm: 65.0% vs 38.3% in the overall period (p = 0.0035), 70.0% vs 51.7% in the acute period (p = 0.0397) and 92.9% vs 74.2% in the delayed period (p = 0.0254). Olanzapine arm also had significantly higher rates of "No significant nausea" and "No nausea" during all 3 time-frames and better QOL. Similar findings were also revealed throughout multiple cycles. Pre-study abnormalities in glucose and lipids occurred in 39.7% and 34.2% of the studied population respectively; there were no differences in these parameters between the two arms at end-of-study assessment. CONCLUSION: The addition of olanzapine to standard aprepitant-based antiemetic regimen provides clinically meaningful improvement in controlling CINV. This was associated with a positive impact on QOL and tolerable toxicity profiles among Chinese breast cancer patients receiving doxorubicin/cyclophosphamide chemotherapy. Further studies on metabolic profiles of breast cancer patients are warranted.

Status of inflammation in relation to health related quality of life in hepatocellular carcinoma patients.

PURPOSE: Both Inflammation and health-related quality of life (HRQoL) are independent prognosticators in HCC patients. We hypothesized that inflammation can cause impairment in HRQoL and investigated the correlation between inflammatory status and HRQoL in HCC patients. METHODS: Clinical, laboratory and HRQoL (using EORTC QLQ-C30, QLQ-HCC18, C30 and HCC18 index-scores) data were prospectively collected from HCC patients at diagnosis. Correlation analyses were performed between HRQoL and inflammation-based markers including C-reactive protein (CRP), CRP/albumin ratio (CRP/alb), Glasgow Prognostic Score (GPS), Inflammation-Based Index (IBI) and Prognostic Index (PI). RESULTS: Among 445 HCC patients, higher inflammatory states were significantly correlated with worse HRQoL. For CRP and CRP/alb ratio, the HRQoL factors with higher correlations included C30 and HCC18 index-scores, certain QLQ-C30 domains and items ('physical functioning', 'role functioning', 'fatigue', 'pain', 'appetite loss') and QLQ-HCC18 items ('fatigue', 'body image', 'nutrition' and 'abdominal swelling'), where the Pearson's correlation coefficients were up to 0.416. Multivariate analyses indicated that worse HRQoL factors were significantly correlated with worse scores in GPS, IBI and PI. CONCLUSION: In HCC patients, inflammatory status correlates with HRQoL at presentation. In particular, relatively stronger correlations with CRP-based markers have been observed in HRQoL scales that assess constitutional symptoms (QLQ-C30 'physical functioning', 'role functioning', 'fatigue', 'appetite loss' and QLQ-HCC18 'fatigue' and 'nutrition') and tumor burden (QLQ-C30 'pain' and QLQ-HCC18 'abdominal swelling' and 'body image'). Future studies are warranted to evaluate whether intervention that reduces inflammation could improve HRQoL in HCC patients.

Dopamine receptor D4 gene -521C/T polymorphism is associated with opioid dependence through cold-pain responses.

Heroin users exhibit abnormal pain sensitivity called opioid-induced hyperalgesia that may weaken their determination to abstain. The dopamine receptor D4 gene (DRD4) is associated with heroin dependence; one of its polymorphisms is a C/T variation 521 bp upstream to the gene (-521C/T). We investigated whether this polymorphism was related to opioid dependence through modulation of cold-pain responses. We recruited 84 heroin-dependent Chinese male subjects and 168 healthy male Chinese controls. Genotyping was performed by PCR-RFLP. A significantly higher T allele frequency was observed in the heroin group (P= 0.041). Of the cohort recruited, 43 current heroin users and 66 controls were further subjected to a cold-pressor test (CPT) to determine their pain threshold and tolerance. TT controls demonstrated a significantly lower pain threshold than did their CC/CT counterparts (P= 0.022) and TT opioid users (P= 0.006). Moreover, CC/CT controls had a significantly higher pain tolerance than TT controls (P= 0.042) and CC/CT opioid users (P= 0.010). The data suggest that DRD4-521C/T plays an important role in opioid dependence through modulating cold-pain responses. TT individuals might have a higher tendency to use opioids because they experience pain less strongly after chronic opioid use.