Dexamethasone-free antiemetic strategy for highly emetogenic chemotherapy: safety and efficacy-pilot study.

OBJECTIVES: Dexamethasone sparing strategies have shown success. The feasibility of a dexamethasone-free antiemetic strategy remains undetermined. A prospective, single-arm, pilot study was planned to determine the efficacy of an olanzapine-based, dexamethasone-free, three-drug antiemetic regimen. METHODS: Chemotherapy naïve, adult patients (≥18 years) who received ondansetron, aprepitant and olanzapine during the first cycle of highly emetogenic chemotherapy were enrolled. The primary endpoint was the rate of complete response (CR: no vomiting and no use of rescue medications) during the overall period (0-120 hours). RESULTS: Out of the total of 101 patients enrolled, most were women (82%) and received anthracycline cyclophosphamide (73%) combination therapy. The rate of CR for the overall period was 65% (95% CI 55.2% to 74.5%). The rate of CR for the acute and delayed period was 79% (95% CI 70% to 86.7%) and 76% (95% CI 66.7% to 84.1%). The rate of nausea control rates for the acute, delayed and overall periods were 34%, 29% and 24%, respectively. The grade I, II and III sedation rates over the 5 days were 8%, 5% and 1%, respectively. CONCLUSIONS: The dexamethasone-free antiemetic strategy showed modest efficacy with low incidence of clinically significant somnolence. There is a need to prospectively investigate the role of dexamethasone in the era of newer potent antiemetics in a randomised fashion. TRIAL REGISTRATION NUMBER: CTRI/2021/07/034813.

Hypo-fractionated accelerated radiotherapy with concurrent and maintenance temozolomide in newly diagnosed glioblastoma: updated results from phase II HART-GBM trial.

BACKGROUND: Glioblastoma (GBM) patients have poor survival outcomes despite treatment advances and most recurrences occur within the radiation field. Survival outcomes after dose escalation through hypofractionated accelerated RT(HART) were evaluated in this study. We previously reported the study's initial results showing similar survival outcomes with acceptable toxicities. Updated results after 5 years are being analysed to determine long-term survival trends. PATIENTS AND METHODS: 89 patients of newly diagnosed GBM after surgery were randomized to conventional radiotherapy (CRT) or HART. CRT arm received adjuvant RT 60 Gy in 30 fractions over 6 weeks and the HART arm received 60 Gy in 20 fractions over 4 weeks, both with concurrent and adjuvant temozolomide. RESULTS: 83 patients were eligible for analysis. After a median follow-up of 18.9 months, the median OS was 26.5 months and 22.4 months in the HART and CRT arms respectively. 5 year OS was 18.4% in the HART arm versus 3.8% in the CRT arm. This numerical difference in overall survival between the two arms was not statistically significant. The median PFS was not significantly different. CONCLUSION: The long-term results of the trial support HART as a promising treatment option with comparable survival outcomes to the current standard of care. Phase III trials are required for further validation of this regimen which has the potential to become the new standard of care in GBM.

Neoadjuvant chemotherapy with or without anthracyclines in combination with single HER2-targeted therapy in HER2-positive breast cancer.

BACKGROUND: Neoadjuvant chemotherapy (NACT) with human epidermal growth factor receptor 2 (HER2) blockade is the preferred approach for treating early and locally advanced HER2-positive breast cancer. There is a lack of robust data comparing pathological complete response (pCR) and survival outcomes in anthracycline-free and anthracycline-containing regimens with single HER2-targeted therapy. OBJECTIVES: The present study retrospectively evaluated pCR between two groups: Single HER2-targeted therapy with and without anthracycline. METHODS: A total of 215 HER2-positive female breast cancer patients were analyzed who received eitheranthracycline-containing EC-TH (epirubicin and cyclophosphamide, followed by docetaxel and trastuzumab)oranthracycline-free TCH [docetaxel, carboplatin and trastuzumab]. Univariate and multivariate analyses identified prognostic factors for survival and pCR.Kaplan Meier survival curvesdetermined disease-free survival(DFS) and overall survival (OS). RESULTS: Baseline characteristics were comparable in both treatment groups. The pCR rate was 30.8% in the anthracycline-containing EC-TH group and 40.9% in the anthracycline-free TCH group; p = 0.140. Disease-free survival at 3 years (65.8% vs. 58.4%) and 5 years (49.2% vs. 55.2%) was similar between EC-TH and TCH groups, respectively (log-rank p = 0.550). Three-year (95.5% vs. 92.5%) and five-year (84.4% vs. 80.8%) OSwere also comparable between both groups (log-rank p = 0.485). The anthracycline-containing EC-TH group had a higher incidence of febrile neutropenia (6.4%. vs. 3.6%) and cardiac adverse events (7.7% vs. 4.4%) than the anthracycline-free TCH group. CONCLUSION: Neoadjuvant anthracycline-free chemotherapy has similar pCR and survival outcomeswith favourable cardiac and non-cardiac adverse effect profiles compared with anthracycline-containing chemotherapy.

Dose-dense neoadjuvant chemotherapy in triple-negative breast cancer: Real-world data from a developing country.

BACKGROUND: Dose-dense adjuvant chemotherapy has been shown to be associated with improved long-term survival outcomes in triple-negative breast cancer (TNBC). However, there is a lacuna of data on the benefits of dose-dense neoadjuvant chemotherapy (NACT) in TNBC. METHODS: This retrospective study included 217 newly diagnosed cases of TNBC treated with a sequential anthracycline and taxane-based NACT, followed by definitive surgery. Study groups consisted of 137 patients who received 3-weekly conventional chemotherapy (cNACT group) and 80 patients with 2-weekly dose-dense NACT (ddNACT group). Pathological complete response (pCR) rates, relapse-free survival (RFS), overall survival (OS), and grade-3/4 chemotoxicities were compared across the groups. RESULTS: No significant difference in the pCR rate (32.8% versus 31.3%; P = 0.808) was observed across the study groups. Relapse rate was lower in the ddNACT group compared to the cNACT group (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27-0.95). However, ddNACT had no RFS advantage over conventional chemotherapy (median RFS: not reached versus 56.1 months in cNACT; hazard ratio: 0.90, 95% CI: 0.52-1.53). OS was also comparable in both the groups with a 3-year survival rate of 78.8% (95% CI: 60.9-89.2) in the ddNACT group versus 84.3% (95% CI: 74.8-90.4) in the cNACT group. Younger age, menopause, the Eastern Cooperative Oncology Group ECOG status, and pCR were significantly associated with OS in our cohort. Grade-3 toxicities were comparable in both groups. CONCLUSIONS: This observational study focusing on ddNACT among TNBC patients demonstrated significant differences in the relapse rate with no survival benefits. Differential effects of ddNACT by tumor presentation (early vs. late), tumor size, tumor biology, and cost-benefits of granulocyte colony-stimulating factor support with such regimens need further exploration.

Effectiveness of Morphine in Managing Refractory Dyspnoea in Patients with Coronavirus Disease (COVID-19).

Opiates are generally used to relieve dyspnoea in advanced diseases such as cancer and lung diseases. However, little is known regarding the safety and efficacy of morphine for refractory dyspnoea in coronavirus disease 2019 (COVID-19) patients. We retrospectively reviewed records of 18 COVID-19-positive patients who were administered morphine for refractory dyspnoea during hospitalisation between May 2021 and June 2021. Details of morphine usage, vital signs, an 11-point dyspnoea numeric rating scale (DNRS) and adverse events at baseline, 24 h and 72 h after the start of treatment were abstracted from records. The final clinical outcome in terms of death or discharge was noted. All patients had severe refractory dyspnoea (DNRS score ≥7) at the time of administration of morphine and had not been relieved from standard care for the past 3 days. In the results, the mean (standard deviation [SD]) age was 47.1 (12) years, male was 13 (72.20%) patients and modified Medical Research Council Grade 4 was present in all 18 patients. The mean (SD) 1st day dose of morphine was 7.03 (1.53) mg and the mean (SD) duration of morphine use was 5.22 (3.00) days. Significant decreases in DNRS, respiratory rate and oxygen saturation were observed 24 h and 72 h after the start of morphine administration. Meanwhile, blood pressure and heart rate were not significantly altered after treatment. The finding of this single-centre retrospective study indicates that morphine may be considered for use in the management of refractory dyspnoea among COVID-19 patients.

Dexmedetomidine Versus Midazolam for Sedation During Medical Thoracoscopy: A Pilot Randomized-Controlled Trial (RCT).

BACKGROUND: Studies comparing the utility of dexmedetomidine with other drugs for sedation during medical thoracoscopy are lacking. In this pilot study, we compared dexmedetomidine with midazolam for sedation in thoracoscopy. METHODS: Consecutive subjects were randomized to receive either dexmedetomidine (n=30) (group D) or midazolam (n=30) (group M). All received fentanyl for procedural analgesia. The primary endpoint was pulmonologist-rated overall procedure satisfaction on the visual analog scale (satisfaction VAS). Key secondary outcomes were pulmonologist-rated cough on VAS (cough VAS), patient-rated faces pain scale scores, change in hemodynamic variables, total additional fentanyl dose, and adverse events during procedure. RESULTS: The satisfaction VAS score (mean±SD) was significantly greater in group D versus group M (7.5±1.4 and 6.5±1.1, respectively) ( P =0.003). The cough VAS scores (mean±SD) were 2.1±1.5 (group D) and 3.1±1.3 (group M) ( P =0.014). The scores (mean±SD) for patient-rated faces pain scale were 2.9±1.8 and 4.2±2.3 ( P =0.019) in group D and group M, respectively. The additional dose of fentanyl administered in group M was significantly greater than in group D ( P =0.001). The responses at the local anesthesia infiltration, skin incision, thoracoscope insertion, and biopsy between both groups were similar. The hemodynamic parameters were comparable in both groups. Also, more patients were willing for repeat thoracoscopy if needed; in the dexmedetomidine group. CONCLUSION: The findings of this pilot RCT indicate that dexmedetomidine may be more efficacious than midazolam for sedation in patients undergoing medical thoracoscopy. These observations need to be confirmed in an adequately powered RCT.