Preemptive use of ibuprofen and desensitizer decreases immediate tooth sensitivity after in-office bleaching: A triple-blind, randomized, placebo-controlled clinical trial.

BACKGROUND: The authors evaluated the synergistic analgesic effect of preemptive administration of 400 mg of ibuprofen (IBU) and potassium fluoride 2% (KF2), both in isolation or combination, on the painful perception of tooth sensitivity after tooth bleaching. METHODS: Fifteen patients participated in this triple-blind, randomized, placebo-controlled clinical trial. The study used a crossover design for drug administration and a split-mouth design for desensitizer agent. Four paired groups were formed: IBU plus KF2 (IBU + KF2); IBU (IBU + placebo KF); KF2 (placebo IBU + KF2), and placebo (placebo IBU + placebo KF). The outcome measure was the perception of tooth sensitivity, assessed using a visual analog scale. Data were collected at 4 different times: immediately after tooth bleaching (baseline) and after 6, 30, and 54 hours. Statistical analysis was performed using the Friedman test and relative risk. RESULTS: IBU plus KF2 was found to be more effective in reducing tooth sensitivity immediately after bleaching (baseline) compared with the placebo group (P < .05). The risk of experiencing moderate or severe tooth sensitivity was approximately 4 times higher in the placebo group than in the IBU plus KF2 group (relative risk, 4.00; 95% CI, 1.01 to 15.81; P = .025). CONCLUSIONS: The combined use of 400 mg of IBU and KF2 appears to be beneficial in managing postbleaching tooth sensitivity. It provides a superior analgesic effect compared with placebo. PRACTICAL IMPLICATIONS: The preemptive administration of IBU plus KF2 reduces tooth sensitivity after tooth whitening when compared with placebo. This clinical trial was registered in the Brazilian Clinical Trials Registry Platform. The registration number is U1111-1249-8191.

Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study.

BACKGROUND: Treatments with survival benefit are greatly needed for women with heavily pretreated metastatic breast cancer. Eribulin mesilate is a non-taxane microtubule dynamics inhibitor with a novel mode of action. We aimed to compare overall survival of heavily pretreated patients receiving eribulin versus currently available treatments. METHODS: In this phase 3 open-label study, women with locally recurrent or metastatic breast cancer were randomly allocated (2:1) to eribulin mesilate (1·4 mg/m(2) administered intravenously during 2-5 min on days 1 and 8 of a 21-day cycle) or treatment of physician's choice (TPC). Patients had received between two and five previous chemotherapy regimens (two or more for advanced disease), including an anthracycline and a taxane, unless contraindicated. Randomisation was stratified by geographical region, previous capecitabine treatment, and human epidermal growth factor receptor 2 status. Patients and investigators were not masked to treatment allocation. The primary endpoint was overall survival in the intention-to-treat population. This study is registered at ClinicalTrials.gov, number NCT00388726. FINDINGS: 762 women were randomly allocated to treatment groups (508 eribulin, 254 TPC). Overall survival was significantly improved in women assigned to eribulin (median 13·1 months, 95% CI 11·8-14·3) compared with TPC (10·6 months, 9·3-12·5; hazard ratio 0·81, 95% CI 0·66-0·99; p=0·041). The most common adverse events in both groups were asthenia or fatigue (270 [54%] of 503 patients on eribulin and 98 [40%] of 247 patients on TPC at all grades) and neutropenia (260 [52%] patients receiving eribulin and 73 [30%] of those on TPC at all grades). Peripheral neuropathy was the most common adverse event leading to discontinuation from eribulin, occurring in 24 (5%) of 503 patients. INTERPRETATION: Eribulin showed a significant and clinically meaningful improvement in overall survival compared with TPC in women with heavily pretreated metastatic breast cancer. This finding challenges the notion that improved overall survival is an unrealistic expectation during evaluation of new anticancer therapies in the refractory setting. FUNDING: Eisai.

Phase II study of eribulin mesylate, a halichondrin B analog, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane.

PURPOSE: Eribulin mesylate (E7389), a nontaxane microtubule dynamics inhibitor, is a structurally simplified, synthetic analog of the marine natural product halichondrin B. This open-label, single-arm, phase II study evaluated efficacy and tolerability of eribulin in heavily pretreated patients with metastatic breast cancer (MBC). METHODS: MBC patients who were previously treated with an anthracycline and a taxane received eribulin mesylate (1.4 mg/m(2)) as a 2- to 5-minute intravenous (IV) infusion on days 1, 8, and 15 of a 28-day cycle. Because of neutropenia (at day 15), an alternative regimen of eribulin on days 1 and 8 of a 21-day cycle was administered. The primary end point was overall response rate. RESULTS: Of the 103 patients treated, the median number of prior chemotherapy regimens was four (range, one to 11 regimens). In the per-protocol population (n = 87), eribulin achieved an independently reviewed objective response rate (all partial responses [PRs]) of 11.5% (95% CI, 5.7 to 20.1) and a clinical benefit rate (PR plus stable disease > or = 6 months) of 17.2% (95% CI, 10.0 to 26.8). The median duration of response was 171 days (5.6 months; range, 44 to 363 days), the median progression-free survival was 79 days (2.6 months; range, 1 to 453 days), and the median overall survival was 275 days (9.0 months; range, 15 to 826 days). The most common drug-related grades 3 to 4 toxicities were as follows: neutropenia, 64%; leukopenia, 18%; fatigue, 5%; peripheral neuropathy, 5%; and febrile neutropenia, 4%. CONCLUSION: Eribulin demonstrated activity with manageable tolerability (including infrequent grade 3 and no grade 4 neuropathy) in heavily pretreated patients with MBC when dosed as a short IV infusion on days 1 and 8 of a 21-day cycle.