Tadalafil in Preventing Erectile Dysfunction in Patients With Prostate Cancer Treated With Radiation Therapy

Inclusion Criteria:

1. Clinical stage T1b-T2b (AJCC, 6th ed.) adenocarcinoma of the prostate within 6 monthsof registration

2. Clinically negative lymph nodes as established by imaging (pelvic ± abdominal CT orMR), nodal sampling, or dissection within 3 months prior to registration. Patientswith lymph nodes equivocal or questionable by imaging are eligible if the nodes are ≤ 1.5 cm. Lymph node assessment is optional, and at investigator discretion, forpatients with Gleason Score <7.

3. No evidence of bone metastases (M0) on bone scan within 3 months prior toregistration. Equivocal bone scan findings are allowed if plain films are negative formetastasis. Bone metastases assessment is optional, and at investigator discretion,for patients with Gleason Score <7.

4. Baseline serum prostatic specific antigen (PSA) value performed with an FDA-approvedassay (e.g., Abbott, Hybritech) within 3 months prior to registration.

-4.1 Any of the following combinations of factors (NOTE: tumor found in 1 or bothlobes on biopsy, but not palpable, will not alter T stage):

• T1b-T2b disease, Gleason Score <7 and serum total PSA that is <20 ng/ml or

• T1b-T2b disease, Gleason Score ≥7 and PSA that is <15 ng/ml

5. Serum total testosterone level prior to the initiation of radiation therapy (RT)within normal range according to institutional guidelines

6. Zubrod Performance Status 0 or 1 (Appendix III)

7. Age ≥ 18 years

8. Treatment that will consist of either external beam RT alone to the prostate ± seminalvesicles only at a dose between 75 Gy and 79.2 Gy or brachytherapy alone (NOTE:treatment with combined external RT and brachytherapy excludes patient participation)

9. Pretreatment (before starting prostate cancer treatment) erectile function as measuredby IIEF Question 1, "How often were you able to get an erection during sexualactivity?" - with responses of:

• "sometimes (about half the time)" [response 3] or

• "most times (much more than half the time)" [response 4] or

• "almost always/always" [response 5]

10. History of prior tadalafil use: Document usual dosage per sexual encounter, date oflast dose, and patient's response (No; Yes—Unsatisfactory Response; Yes—SatisfactoryResponse). Regardless of past experience, the patient is eligible if he agrees toadhere to protocol and take only tadalafil or placebo prescribed on study.

11. Although patients with partners are targeted for recruitment, patients withoutpartners or without partners willing to participate are eligible. Patients (andspouses/partners, if willing to participate) must be able to provide study-specificinformed consent.

Exclusion Criteria:

1. The patient's participation in another medical research study that involves thetreatment of ED

2. Previous or concomitant invasive cancer (American Joint Committee on Cancer [AJCC]Stage >0), other than localized basal cell or squamous cell skin carcinoma (AJCC Stage 0-II), or a hematological malignancy (e.g., leukemia, lymphoma, myeloma) unlesscontinually disease free for at least 5 years

3. History of myocardial infarction within the last year

4. Heart failure in the last 6 months

5. Uncontrolled arrhythmias, hypotension (<90/50mm Hg), or uncontrolled hypertension (>170/100 mm Hg)

6. Stroke within the last 6 months

7. Use of luteinizing hormone-releasing hormone (LHRH) agonist androgen suppression (e.g., Lupron, Zoladex), anti-androgen (e.g., Casodex, Eulexin, Nilandron), orestrogenic (e.g., diethylstilbestrol) agents within the last 6 months

8. Current use of any organic nitrate or as needed nitrates (e.g., use of nitroglycerin)

9. Current use of cimetidine, ketoconazole, itraconazole, erythromycin, or ritonavir

10. Known moderate to severe renal insufficiency or end-stage renal disease

11. Known severe hepatic impairment

12. Use of mechanical (vacuum) devices, intracorporeal, intraurethral, topical, or oral (sildenafil, tadalafil, vardenafil) agents as therapy for ED or supplements to enhancesexual function within 5-7 days prior to the start of RT. Patients who discontinuethese therapies remain eligible if they can meet eligibility criteria

13. Pretreatment (before starting prostate cancer treatment) ED as measured by IIEFQuestion 1, "How often were you able to get an erection during sexual activity?" -with responses of:

• "no sexual activity" [response 0] or

• "almost never/never" [response 1] or

• "a few times (much less than half the time)" [response 2]

14. Prior penile implant or history of bilateral orchiectomy

15. Prior prostatectomy, prostatic cryosurgery or high-intensity focused ultrasound (HIFU), radionuclide prostate brachytherapy, or chemotherapy for prostate cancer

16. Prior or anticipated combined external RT and brachytherapy

17. Prior or anticipated external RT to the pelvic ± para-aortic lymph nodes

18. Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for DiseaseControl and Prevention (CDC) definition; note, however, that HIV testing is notrequired for entry into this protocol. The need to exclude patients with AIDS fromthis protocol is necessary because the treatments involved in this protocol may besignificantly immunosuppressive. Protocol-specific requirements may also excludeimmunocompromised patients.

19. Anatomical genital abnormalities or concurrent conditions that in the estimation ofthe physician would prohibit sexual intercourse or prevent study completion

20. Major medical or psychiatric illness which, in the opinion of the investigator, wouldprevent completion of treatment or would interfere with follow-up