Steroid Mouth Rinse Prevents Stomatitis with Everolimus

San Antonio, TX—A steroid mouthwash can reduce the incidence of stomatitis associated with the use of everoli­mus. Data from the first prospective trial of prophylactic use of a steroid mouth rinse demonstrated a 26% incidence of stomatitis among patients with metastatic breast cancer who used the mouth rinse versus 67% in historical controls, said Vicky E. Jones, MD, at the 2015 San Antonio Breast Cancer Symposium.

The ongoing phase 2 study evaluated 2 different steroid-based mouth rinses for the prevention or amelioration of oral stomatitis in postmenopausal patients within the US Oncology Network with hormone receptor (HR)-positive metastatic breast cancer treated with everolimus.

“As we are expanding the use of everolimus into [the] metastatic breast cancer arena, stomatitis became a toxicity that needed to be addressed,” said Dr Jones, US Oncology Research, Inc, The Woodlands, TX. “There were smaller studies that reported that steroid-containing mouth solutions seemed to make a difference, so the study was set up to look at 2 different mouth rinses. They were both compounded for purposes of the study so that they would be the same across all the study sites.”

Patients were randomized to 12 weeks of treatment with 1 of 2 oral rinses. In arm 1, patients were instructed to rinse with a 480-mL recipe containing 320 mL of oral Benadryl, 2 g of tetracycline, 80 mg of hydrocortisone, and 40 mL of nystatin suspension. Arm 2 was assigned to an oral solution of prednisolone 15 mg/5 mL.

Patients were instructed to swish and expectorate 10 mL of the assigned mouthwash 4 times each day. If symptoms of pharyngitis developed, they could also gargle with the assigned rinse 4 times per day.

The primary objective was to determine the incidence of grade ≥2 stomatitis during the first 12 weeks of treatment. A total of 48 patients were randomized, and 47 received the study treatment.

“Stomatitis tends to be an early phenomenon with everolimus, so the 12 weeks covered that time period pretty well,” said Dr Jones.

The incidence of all-grade stomatitis and related events was 26%. The incidence of grade ≥2 stomatitis was 9%. Of the 4 patients with grade ≥2 stomatitis, 1 developed it within the first 2 weeks and 3 within the first 30 days. No patient experienced grade 3 stomatitis.

For 3 of the 4 patients who developed grade ≥2 stomatitis, no action was taken, and an everolimus dose was delayed in the fourth patient. No patients required everolimus dose reduction.

One patient developed oral candidiasis while on the mouth rinse. No patients stopped the prophylactic rinse due to treatment-related toxicity.

By comparison, in the BOLERO-2 trial in patients with HR-positive metastatic breast cancer who were treated with exemestane plus everolimus, the incidence of all-grade stomatitis or related adverse events was 67%, with 24% developing grade 2 and 8% developing grade 3 stomatitis. In BOLERO-2, one-fourth of patients required everolimus dose reduction for stomatitis, noted Dr Jones.

“The bottom line is that the mouth rinses were well tolerated with very few side effects,” she said. “Only one patient developed thrush, and nobody stopped because of toxicity of the mouth rinse.”

The incidence of stomatitis on each study arm will be available when all patients in the trial have been accrued.

Reference

Jones VE, Jensen LL, McIntyre KJ, et al. Evaluation of miracle mouthwash (MMW) plus hydrocortisone versus prednisolone mouth rinses as prophylaxis for everoli­mus-associated stomatitis: preliminary results of a randomized phase II study. Poster presented at: 2015 San Antonio Breast Cancer Symposium; December 5-8, 2015; San Antonio, TX. Abstract P1-15-06. http://sabcs15.posterview.com/nosl/i/P1-15-06. Accessed January 4, 2016.