Efficacy and Toxicity of Bicalutamide and Dutasteride vs. Standard Care for Prostate Cytoreduction for Brachytherapy

Condition(s) targeted: Prostate Cancer; Erectile Dysfunction; Lower Urinary Tract Symptoms

Intervention: administration of a LHRH agonist and Bicalutamide (Drug); administration of Bicalutamide, Dutasteride and Tamoxifen (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Centre Hospitalier Universitaire de Québec, CHU de Québec

Official(s) and/or principal investigator(s):
Andre-Guy Martin, MD, Principal Investigator, Affiliation: CHUQ-Hotel-Dieu de Québec

The purpose of this study is to determine if a combination of neoadjuvant dutasteride and bicalutamide has the same efficacy and less toxicity than standard treatment with an LHRH agonist and bicalutamide for prostate cytoreduction prior to permanent implant brachytherapy.

Official title: Phase II Study of Bicalutamide and Dutasteride for Prostate Cytoreduction Prior to Permanent Implant I-125 Prostate Brachytherapy

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment

Primary outcome: Total prostate volume

Secondary outcome:

EPIC questionnaire urinary function and bother scores

EPIC questionnaire sexual function and bother scores

EPIC questionnaire bowel function and bother scores

EPIC questionnaire hormonal function and bother scores

IPSS scores

Acute urinary retention rates

SF-12 Quality of life questionnaire results

Rate of gynecomastia and breast tenderness

Serum testosterone

Anemia

Abnormal liver function tests

Serum PSA

Adverse events recording

Detailed description: Permanent implant prostate brachytherapy is recognized as the treatment method for prostate cancer that results in the least amount of sexual side effects including erectile dysfunction (ED). However prostate brachytherapy is often limited to patients with a prostate volume less than 50cc because of dosimetric and technical considerations. To counter this fact patients with a prostate larger than 50cc are offered neoadjuvant hormonal therapy to reduce their prostate volume to a value less than 50cc. The pharmacological method most often employed involves treatment with an LHRH agonist, which also involves multiple adverse effects for patients including ED in the majority of patients. This approach may also involve other disadvantages including a possibility of increased cardiovascular mortality a possible increase in urinary toxicity and a reduction in health-related quality of life in patients treated with neoadjuvant hormonal therapy. Despite theses facts, neoadjuvant hormonal therapy remains essentially the sole method used to reduce prostate volume prior to prostate brachytherapy. One study has evaluated the efficacy of a neoadjuvant regimen without an LHRH agonist, comprised of Dutasteride and Bicalutamide to reduce prostate volume. This treatment could theoretically have fewer effects on sexual function and quality of life and could also possibly reduce urinary toxicity of brachytherapy. Nonetheless, these factors have never been evaluated. The cytoreductive efficacy of Bicalutamide and Dutasteride have never been directly compared to standard treatments. The current study is necessary to determine the effects of a neoadjuvant regimen of Bicalutamide and Dutasteride on prostate volume, sexual function, urinary toxicity and quality of life as compared to standard treatment. If it can be determined that there is an advantage with Bicalutamide and Dutasteride this regimen could become a standard of care for prostate cytoreduction prior to brachytherapy.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Male.

Criteria:

Inclusion Criteria:

- Male sex

- Diagnosis of prostate adenocarcinoma as confirmed by prostate biopsy

- Prostate cancer with stage T1a, T1b T2a or T2b Nx Mx as determined by clinical

examination

- Gleason score of 6 or less or 7 (3+4)*

* If Gleason score is 7(3+4) patient must have less than 30% of biopsied tissue positive

- Serum PSA of ≤ 15ng/ml during the month before study entry

- Prostate volume ≥ 45cc

- Normal serum testosterone during the month before study entry

- Availability for treatment and follow-up visits

- Having signed required consent form before study entry

Exclusion Criteria:

- Abnormal Liver Function tests (>2x normal AST or ALT and/or >1. 5x normal bilirubin)

- Prostate volume less than 50 cc

- History of hormonal treatment including any of the above: LHRH agonists,

antiandrogens during the year before study entry

- Use of a 5 alpha reductase inhibitor for more than one month during the year prior to

study entry

- History of pelvic irradiation

- History of past chemotherapy

- History of TURP

- History of past treatment for prostate cancer

- Known hypersensitivity to Dutasteride or Bicalutamide

- Co-morbid disease possibly compromising treatment compliance

- History of DVT or pulmonary embolism

- Anticoagulation with coumarin

- Inability to give consent

CHUQ- Hotel-Dieu de Quebec, Quebec G1R 2J6, Canada

Starting date: March 2009
Last updated: April 14, 2015