Oral pilocarpine to treat vaginal xerosis associated with chemotherapy-induced amenorrhea in pre-menopausal women

Abstract

8099 Background: Chemotherapy-induced amenorrhea frequently results in side effects common to those experienced in menopause; vaginal dryness (VD) and its related symptoms are prominent examples. Although many of these side effects respond to the use of estrogen replacement therapy (ERT), many cancer survivors choose to not chance the risks linked with ERT. Previous results in a placebo-controlled Phase III study treating xeroses associated with Sjögren's syndrome with oral pilocarpine (OP){Salagen® Tablets}demonstrated impressive improvement in VD, P≤0.02 (25% vs.14%):Vivino et al; Arch Intern Med. 1999;159. Methods: A 12-week, open-label pilot study was conducted using OP (5mg./qid) in pre-menopausal women with VD caused by the effects of high cumulative dose cyclophosphamide on ovarian function. Study enrollment required a minimum 2 month history of VD and 4 months status-post chemotherapy. The primary endpoint of this study was a global assessment of VD measured on a standard visual analog scale (VAS), at 6 and 12 weeks of treatment, or at final study visit if prior to week 12. Participants were asked to characterize their VD at these visits compared to their VD before treatment with OP; each participant acted as her own control. Results: The pre-study expectation was for a 25 mm (absolute) improvement in the participants' VAS by end of study. Four of four evaluable participants treated with OP experienced a marked clinical improvement in VD.Three responders recorded ≥40mm absolute gain in VAS, the fourth gained ≥28mm. Conclusions: OP, a well-tolerated muscarinic agonist was able to stimulate remaining mucus and other moisture producing cells in the vaginal mucosa & muscularis to the extent that a marked clinical improvement in VD was experienced by each of the study participants. The only AEs experienced were mild and of the known side effects of OP and did not interfere with treatment. These results warrant further investigation as a possible treatment for symptomatic relief of this difficult problem. No significant financial relationships to disclose.