Evaluation of Miracle Mouthwash plus Hydrocortisone Versus Prednisolone Mouth Rinses as Prophylaxis for Everolimus-Associated Stomatitis: A Randomized Phase II Study.

BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitor-associated stomatitis (mIAS) is a frequent adverse event (AE) associated with mTOR inhibitor therapy and can impact treatment adherence. The objectives are to evaluate two steroid-based mouthrinses for preventing/ameliorating mIAS in patients with metastatic breast cancer (MBC) treated with everolimus. MATERIALS AND METHODS: This prospective, randomized phase II study enrolled 100 postmenopausal patients with hormone receptor-positive MBC within the US Oncology Network who were initiating therapy with an aromatase inhibitor + everolimus (AIE; 10 mg/day). Patients were randomized to prophylactic therapy with one of two oral rinses (Arm 1: Miracle Mouthwash [MMW] 480 mL recipe: 320 mL oral Benadryl [diphenhydramine; Johnson & Johnson, New Brunswick, NJ, USA], 2 g tetracycline, 80 mg hydrocortisone, 40 mL nystatin suspension, water; or Arm 2: prednisolone [P] 15 mg/5 mL oral solution, 1.8% alcohol). Patients were instructed to swish/expectorate 10 mL of the assigned rinse for 1-2 minutes four times daily starting with day 1 of AIE treatment, for the first 12 weeks. RESULTS: A total of 100 patients received treatment (49 MMW; 51 P). The incidence of stomatitis/oral AEs during the first 12 weeks was 35% (n = 17/49) and 37% (19/51) in the MMW and P arms, respectively. The incidence of grade 2 oral AEs was 14% (7/49) and 12% (6/51) with MMW or P, respectively. There were two grade 3 oral AEs (MMW arm) and no grade 4 events. There was one everolimus dose reduction (MMW) and six dose delays (four MMW, two P) and one dose reduction + delay (MMW) during the first 12 weeks of treatment. No patients stopped steroid mouthwash therapy because of rinse-related toxicity. CONCLUSION: Prophylactic use of steroid-containing oral rinses can prevent/ameliorate mIAS in patients with MBC treated with AIE. MMW + hydrocortisone is an affordable option, as is dexamethasone oral rinse. IMPLICATIONS FOR PRACTICE: This prospective phase-II study showed that two steroid-containing mouthrinses substantially reduced incidences of all-grade and grade ≥2 stomatitis and related oral adverse events (AEs), and the number of everolimus dose-delays and/or dose-reduction in metastatic breast cancer (MBC) patients receiving everolimus treatment plus an aromatase inhibitor. Both oral rinses were well tolerated and demonstrated similar efficacy. Prophylactic use of steroid mouth rinse provides a cost-effective option that substantially decreases the incidence and severity of mammalian target of rapamycin (mTOR) inhibitor-associated stomatitis and related oral AEs as well as the need for dose modification in MBC patients undergoing treatment with an mTOR inhibitor.

Ramucirumab With Eribulin Versus Eribulin in Locally Recurrent or Metastatic Breast Cancer Previously Treated With Anthracycline and Taxane Therapy: A Multicenter, Randomized, Phase II Study.

BACKGROUND: Use of antiangiogenic agents in treatment of metastatic breast cancer (MBC) remains controversial. We evaluated the efficacy and safety of ramucirumab and eribulin versus eribulin alone as third- to fifth-line therapy in women with advanced breast cancer. PATIENTS AND METHODS: In this randomized (1:1), open-label, phase II study, US women aged 18 years or older with 2 to 4 previous chemotherapy regimens for locally recurrent or MBC, previous anthracycline and taxane treatment, and Eastern Cooperative Oncology Group performance status of 0 or 1 received ramucirumab with eribulin or eribulin alone in 21-day cycles (eribulin 1.4 mg/m2 intravenously on days 1 and 8; ramucirumab 10 mg/kg intravenously on day 1). Randomization was stratified according to previous antiangiogenic therapy and triple-negative status. The primary end point was progression-free survival (PFS) in the intention to treat population. RESULTS: One hundred forty-one women were randomized to ramucirumab with eribulin (n = 71) or eribulin alone (n = 70). Median PFS for ramucirumab with eribulin was 4.4 months (95% confidence interval [CI], 3.1-6.7) compared with 4.1 months (95% CI, 3.2-5.6) for eribulin (hazard ratio [HR], 0.83; 95% CI, 0.56-1.23; P = .35). Median overall survival in patients who received ramucirumab with eribulin was 13.5 months (95% CI, 10.4-17.9) compared with 11.5 months (95% CI, 9.0-17.3) in patients who received eribulin alone (HR, 0.91; 95% CI, 0.59-1.41; P = .68); objective response rate was 21% (13 of 62 patients) for the combination and 28% (17 of 60 patients) for eribulin alone. No unexpected toxicity was identified for the combination. CONCLUSION: Ramucirumab combined with eribulin did not significantly improve PFS in advanced MBC.

A prognostic index for survival among mechanically ventilated hematopoietic cell transplant recipients.

The prognosis of recipients of allogeneic hematopoietic cell transplantation (HCT) who require mechanical ventilation (MV) has historically been poor. Of 883 adults undergoing allogeneic HCT at the University of Minnesota between 1998 and 2009, 179 (20%) required MV before day 100 posttransplantation. We evaluated the outcomes of these patients to develop a prognostic index to predict the 100-day post-MV overall survival (OS) based on factors present at the time of MV. The 179 patients were divided at random into a training set (n = 119) and a validation set (n = 60). The 100-day postventilation OS was 17% for the total population. Multivariate Cox regression on the training set identified creatinine <2 mg/dL and platelet count >20 × 10(9)/L as significant predictors of better OS. Recursive partitioning classified patients with these good prognostic criteria into class A (n = 76); all other patients were classified as class B (n = 103). Among class A patients, 100-day OS was 29% in the training set and 30% in the validation set. Corresponding OS in class B patients was 5% and 15%, respectively. This prognostic index should help guide physicians in counseling HCT patients and their families regarding the use of MV and potential outcomes.

Malignant hyperthermia associated with diabetic hyperosmolar hyperglycemic nonketotic state in a young man.

Malignant hyperthermia (MH) is a rare complication that often leads to adverse outcomes, catastrophic events, or death. Although various risk factors and underlying diseases are associated with this condition, unusual presentations may be missed. Malignant hyperthermia is an uncommon complication encountered during the treatment of patients with diabetic ketoacidosis. We present a case of an MH-like syndrome in a young Hispanic man who was diagnosed with new-onset diabetes mellitus and hyperglycemic hyperosmolar nonketotic state. The patient had no obvious risk or precipitating factors for MH.