Perioperative chemotherapy for urothelial carcinoma of the upper urinary tract: A systematic review and meta-analysis.

INTRODUCTION: Upper tract urothelial carcinomas are rare malignancies with differences in anatomy and biology requiring therapeutic strategies that differ from bladder cancer. The role of perioperative systemic therapy in this disease remains uncertain with limited data to support its use. A systematic review of the literature and meta-analysis was therefore undertaken to provide more information and guide clinical practice. METHODS: A literature search was performed using Embase and Medline databases with additional searches performed manually using terms associated with upper tract urothelial malignancies. Data was extracted from studies of patients that underwent nephrouretectomy for the management of upper tract urothelial carcinoma and received either neoadjuvant or adjuvant systemic therapy. Overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS) were summated and analyzed using Cochrane Revman software Version 5.3. RESULTS: There were 13 comparative studies and no randomized studies identified for data extraction; 11 adjuvant and 2 neoadjuvant with 1170 patients receiving perioperative systemic therapy and 3472 controls that did not. Perioperative chemotherapy was associated with improved OS (HR 0.75, 95%CI 0.57-0.99), DFS (HR 0.54, 95%CI 0.32-0.92), and CSS (HR 0.69, 95%CI 0.42-1.15). CONCLUSIONS: The available data suggests that perioperative systemic therapy is associated with improved survival in patients with upper tract urothelial cancer.

Canadian Cancer Trials Group (CCTG) IND211: A randomized trial of pelareorep (Reolysin) in patients with previously treated advanced or metastatic non-small cell lung cancer receiving standard salvage therapy.

OBJECTIVES: Pelareorep (reolysin), a Dearing strain of reovirus serotype 3, has demonstrated oncolytic activity as single agent and synergy with chemotherapy. We evaluated pelareorep, combined with standard second-line chemotherapy in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: This randomized phase II trial enrolled patients with advanced or metastatic NSCLC after first line chemotherapy. After a safety run-in, patients were randomized 1:1 to chemotherapy (pemetrexed [500 mg/m2, non-squamous], or docetaxel [75 mg/m2], day 1 every 21 days]) +/- pelareorep (4.5 × 1010 TCID50, days 1-3 every 21 days), stratified by EGFR mutation status. The primary outcome was progression free survival (PFS) of patients randomized to chemotherapy + pelareorep vs. chemotherapy alone. Secondary outcomes included overall survival, objective response rate and exploratory translational analyses. RESULTS: Between October 2012 and August 2015, 166 patients were enrolled (14 to the safety run in). Pelareorep did not improve the PFS vs. single agent chemotherapy (median PFS 3.0 months, 95% confidence interval [CI] 2.6-4.1) vs. 2.8 months (95% CI 2.5-4.0), hazard ratio (HR) 0.90 (95% CI 0.65-1.25), P = 0.53). Neither KRAS or EGFR mutation was associated with improved PFS, but STK11 mutations did appear to have an association with improved PFS (HR 0.29 [0.12-0.67); as did PIK3CA mutation (HR 0.45 [0.22-0.93]). The combination was tolerable, although associated with increased rates of neutropenic fever. CONCLUSION: The addition of pelareorep to second-line chemotherapy did not improve the PFS of patients with NSCLC. The three-day pelareorep schedule was tolerable. Further research is needed to evaluate the potential benefit in molecular subtypes of NSCLC.

Randomized trial of oral versus intravenous acetaminophen for postoperative pain control.

PURPOSE: Results of a study comparing pain control outcomes with preoperative oral versus intraoperative i.v. acetaminophen use in adults undergoing total hip or knee arthroplasty are reported. METHODS: A single-center, randomized, placebo-controlled, equivalence trial was conducted. Patients were assigned (1:1) to receive 2 500-mg capsules of acetaminophen before surgery, with an i.v. placebo infusion during surgery (the oral group), or 2 oral placebo capsules followed by an i.v. infusion of acetaminophen 1,000 mg/100 mL (the i.v. group). Patients were followed after postanesthesia care unit (PACU) admission up to 24 hours postoperatively. RESULTS: Among 486 patients included in a modified intention-to-treat analysis (mean ± S.D. age, 66.3 ± 9.4 years), there were no significant differences in preoperative and intraoperative use of pain medication between the oral and i.v. groups. Postoperative opioid use in morphine milligram equivalents (MMEs) was equivalent in the oral and i.v. groups (i.e., the mean difference in median MME values was within the prespecified equivalence margin), with no significant between-group differences in mean pain scores over 24 hours. CONCLUSION: In patients undergoing hip or knee arthroplasty, oral acetaminophen given preoperatively was equivalent to i.v. acetaminophen administered in the operating suite in controlling pain in the immediate postoperative period. I.V. acetaminophen was not superior to oral acetaminophen in reducing postoperative nausea and vomiting, time to ambulation, time to first dose of as-needed pain medication, length of PACU stay, or total length of hospital stay.