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.

A protocol for the use of enoxaparin during pregnancy: results from 85 pregnancies including 13 multiple gestation pregnancies.

Many practitioners consider low-molecular-weight heparin (LMWH) an alternative to unfractionated heparin, although there are limited safety data regarding maternal and fetal outcomes in patients using an LMWH during pregnancy. A retrospective chart review was performed on 72 patients with thrombophilia exposed to the LMWH, enoxaparin, during pregnancy. Eighty-five pregnancies resulted in 93 of 99 potential live births. Eleven of 12 twin pregnancies and one triplet pregnancy were successful. One preterm live birth infant of 33 weeks' gestation did not survive. Three patients with thrombophilia spontaneously aborted. A patient receiving injectable fertility treatment had spontaneously aborted one twin at 5 weeks' gestation. One patient terminated the pregnancy after discovering the presence of Down's syndrome. The mean maximum dose required to achieve a therapeutic anti-Xa level of 0.2-0.4 IU/mL at 5 to 6 hours following administration, was 38.1 mg every 12 hours (median 35 mg, range 30-75 mg every 12 hours). The mean anti-Xa level was 0.28 IU/mL (median 0.3, range 0.05-0.8 IU/mL). A total of nine patients experienced bleeding events, two requiring discontinuation of enoxaparin for the remainder of the pregnancy. Two patients experienced injection site reactions requiring discontinuation of enoxaparin. Three patients developed preeclampsia, two placenta abruptio, and one placenta previa. No thromboembolic complications or osteoporotic fractures had occurred. Enoxaparin was safe and effective for preventing thromboembolism and adverse obstetrical complications in our patients, including 12 of 13 multiple gestation pregnancies.