Pilocarpine in Treating Vaginal Dryness in Patients With Breast Cancer

• Toxicities [ Designated as safety issue: Yes ]
• Quality of life [ Designated as safety issue: No ]

RATIONALE: Pilocarpine may decrease vaginal dryness and improve quality of life in patients with breast cancer It is not yet known whether pilocarpine is more effective than a placebo in treating vaginal dryness in patients with breast cancer.

PURPOSE: This randomized phase III trial is studying pilocarpine to see how well it works compared to a placebo in treating vaginal dryness in patients with breast cancer.

OBJECTIVES:

Primary

• Determine the effectiveness of pilocarpine hydrochloride for alleviation of vaginal dryness in patients with breast cancer.

Secondary

• Evaluate any toxicities arising from pilocarpine hydrochloride in these patients.
• Evaluate quality of life of these patients treated with pilocarpine hydrochloride.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to age (18 to 45 vs 46 to 55 vs 56 to 65 vs > 65), concurrent tamoxifen therapy (yes vs no vs unknown [e.g., on a blinded clinical study]), concurrent aromatase inhibitor therapy (yes vs no vs unknown [e.g., on a blinded clinical study]), and perception of severity of vaginal symptoms at baseline (mild vs moderate vs severe). Patients are randomized to 1 of 4 treatment arms.

• Arm I: Patients receive oral pilocarpine hydrochloride once a day for 3 days, twice a day for 3 days, three times a day for 3 days, and then 4 times a day for up to 6 weeks in the absence of unacceptable toxicity.
• Arm II: Patients receive oral pilocarpine hydrochloride once a day for 3 days and then twice a day for up to 6 weeks in the absence of unacceptable toxicity.
• Arm III: Patients receive oral placebo once a day for 3 days, twice a day for 3 days, three times a day for 3 days, and then 4 times a day for up to 6 weeks in the absence of unacceptable toxicity.
• Arm IV: Patients receive oral placebo once a day for 3 days and then twice a day for up to 6 weeks in the absence of unacceptable toxicity.

Quality of life is assessed at baseline and then weekly for 6 weeks.

PROJECTED ACCRUAL: A total of 192 patients will be accrued for this study.

• Breast Cancer
• Sexual Dysfunction
• Sexuality and Reproductive Issues

• Drug: pilocarpine hydrochloride
  Given orally
• Other: placebo
  Given orally

• Experimental: Arm I
  Patients receive oral pilocarpine hydrochloride once a day for 3 days, twice a day for 3 days, three times a day for 3 days, and then 4 times a day for up to 6 weeks in the absence of unacceptable toxicity.
  Intervention: Drug: pilocarpine hydrochloride
• Experimental: Arm II
  Patients receive oral pilocarpine hydrochloride once a day for 3 days and then twice a day for up to 6 weeks in the absence of unacceptable toxicity.
  Intervention: Drug: pilocarpine hydrochloride
• Placebo Comparator: Arm III
  Patients receive oral placebo once a day for 3 days, twice a day for 3 days, three times a day for 3 days, and then 4 times a day for up to 6 weeks in the absence of unacceptable toxicity.
  Intervention: Other: placebo
• Placebo Comparator: Arm IV
  Patients receive oral placebo once a day for 3 days and then twice a day for up to 6 weeks in the absence of unacceptable toxicity.
  Intervention: Other: placebo

• Loprinzi CL, Balcueva EP, Liu H, et al.: A phase III randomized, double-blind, placebo-controlled study of pilocarpine for vaginal dryness: NCCTG study N04CA. [Abstract] J Clin Oncol 28 (Suppl15): A-9024, 2010.
• Loprinzi CL, Balcueva EP, Liu H, Sloan JA, Kottschade LA, Stella PJ, Carlson MD, Moore DF Jr, Zon RT, Levitt R, Jaslowski AJ. A phase III randomized, double-blind, placebo-controlled study of pilocarpine for vaginal dryness: North Central Cancer Treatment group study N04CA. J Support Oncol. 2011 May-Jun;9(3):105-12.

DISEASE CHARACTERISTICS:

• Meets 1 of the following criteria:

  • History of breast cancer (currently no evidence of disease)
  • Unwilling to take vaginal estrogen due to fear of an increased risk of breast cancer

• Significant vaginal complaints, defined as persistent vaginal dryness and/or itching of sufficient severity to make a patient desire therapeutic intervention

  • Symptoms present ≥ 2 months prior to randomization
• No active vaginal infection
• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Female
• Postmenopausal or no childbearing potential
• Life expectancy > 6 months
• SGOT < 1.5 times upper limit of normal (ULN) for the past year
• Creatinine ≤ 1.5 times ULN for the past year
• Able to complete questionnaire(s) alone or with assistance

• No diagnosis of any of the following:

  • Asthma
  • Chronic obstructive pulmonary disease
  • Coronary artery disease
  • Narrow angle glaucoma
  • Known cholelithiasis
  • Vulvar and vaginal dysplasia
  • Essential vulvodynia
  • Vulvar vestibulitis
  • Vaginal prolapse
  • Bartholin cyst/abscess
  • Lichen sclerosis
  • Lichen planus of the vulvovaginal region
  • Desquamative vaginitis
• No known history of cardiac arrhythmia
• No history of Bartholin gland surgery
• No acute iritis

PRIOR CONCURRENT THERAPY:

• No initiation or discontinuation of tamoxifen or aromatase inhibitors ≤ 2 months prior to study randomization or plans to initiate or discontinue any of these medications during the 6-week study period

• More than 1 week since prior vaginal preparations*

  • If patient has used vaginal preparations during the previous week but is planning to stop, then the patient may enter the study with plans to start with pretreatment questionnaire 1 week later NOTE: *Lubricants used during sexual intercourse are allowed

• No prior radical pelvic surgery

  • Total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH/BSO) allowed
• No prior pilocarpine hydrochloride
• No prior or concurrent pelvic radiotherapy
• More than 4 weeks since prior and no concurrent estrogen products
• No concurrent vaginal preparations (including any over-the-counter or herbal preparations)
• No other concurrent anticholinergics
• No concurrent chemotherapy
• No concurrent hormonal therapy, including progestationally-coated intrauterine devices (IUDs)
• No concurrent pharmacologic soy preparations
• No concurrent surgery and/or radiotherapy for recurrent cancer
• No beta adrenergic antagonists
• No other concurrent treatment for vaginal dryness