Pentoxifylline, Atorvastatin, and Vitamin E in Treating Patients With Erectile Dysfunction After Radiation Therapy for Prostate Cancer

M.D. Anderson Cancer Center

Status and phase: Completed; Phase 2

Conditions: Impotence; Erectile Dysfunction, CTCAE; Prostate Adenocarcinoma; Male Erectile Disorder

Treatments: Drug: Atorvastatin; Drug: Pentoxifylline; Dietary Supplement: Vitamin E Compound

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03830164

NCI-2019-00235 (Registry Identifier)

2018-0785 (Other Identifier)

Details and patient eligibility

About

This phase II trial studies how well pentoxifylline, atorvastatin, and vitamin E (PAVE) work in treating patients with erectile dysfunction after radiation therapy for prostate cancer. Atorvastatin may reduce high cholesterol. Pentoxifylline and vitamin E may enhance blood flow. Giving PAVE may work better in treating prostate cancer patients with post-radiation therapy erectile dysfunction.

Full description

PRIMARY OBJECTIVE:

I. To estimate the proportion of patients who achieve a clinically significant improvement in erectile dysfunction (ED) when treated with a combination of atorvastatin or patient's currently prescribed statin, vitamin E, and pentoxifylline (PAVE).

SECONDARY OBJECTIVES:

I. To report the safety profile of PAVE. II. To report the rate of choosing other ED treatments after PAVE.

OUTLINE:

Patients receive atorvastatin orally (PO) once daily (QD) for up to 6 weeks in the absence of disease progression or unacceptable toxicity. Beginning week 7, patients receive atorvastatin PO QD, vitamin E PO QD, and pentoxifylline PO thrice daily (TID) for up to 12 months in the absence of disease progression or unacceptable toxicity.

Enrollment: 14 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate
• Previous radiation therapy (any form) with curative intent for prostate cancer
• Erectile dysfunction, as determined by an International Index of Erectile Function (IIEF)-5 score of < 22
• Normal testosterone (including men on testosterone replacement), defined as testosterone > 150 ng/dl at the time of screening
• Karnofsky Performance Status (KPS) >= 70, or Eastern Cooperative Oncology Group (ECOG) 0-2
• Patients may be taking an HMG-coA-reductase inhibitor
• Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 X upper limits of normal (ULN)
• Creatinine kinase < 5 times ULN
• Normal renal function is defined as creatinine clearance >= 30 ml/min via the Cockcroft Gault formula

Exclusion criteria

• No androgen deprivation therapy within the past 12 months
• No contraindication to an HMG-coA-reductase inhibitor, vitamin E or pentoxifylline
• Not currently taking cyclosporine, the human immunodeficiency virus (HIV) protease inhibitors, hepatitis C protease inhibitors, gemfibrozil, other fibrates, clarithromycin, itraconazole or strong inhibitors of CYP3A4
• No recent cerebral or retinal hemorrhage that in the opinion of the treating physician would make PAVE unsafe (within 6 months)
• No current chemotherapy during study participation
• No active liver or muscle disease that in the opinion of the treating physician would make PAVE unsafe
• No prior radical prostatectomy, cystoprostatectomy, abdominoperineal resection or retroperitoneal lymph node dissection
• Not currently taking a 5PDE inhibitor nor have used one within 30 days of enrolling in the study
• No recent deep venous thrombosis, myocardial infarction or pulmonary embolism (within 6 months) requiring continued anticoagulation other than aspirin (acetylsalicylic acid [ASA])
• No cardiac arrhythmias or artificial heart valves requiring anticoagulation other than ASA
• No concurrent drugs with anti-platelet therapy properties (e.g., P2Y12 inhibitors, non-steroidal anti-inflammatory agents, selective serotonin reuptake inhibitors) other than low dose ASA (81 mg/d)
• Not currently taking high dose statin therapy, defined as rosuvastatin > 10 mg/d or atorvastatin > 40 mg/d
• Not currently taking theophylline
• No history of active peptic ulcer disease in the past 6 months
• No history of intolerance to pentoxifylline or methylxanthines such as caffeine, theophylline and theobromine that in the opinion of the treating physician would make PAVE unsafe
• No concurrent use of CYP1A2 inhibitors (e.g., ciprofloxacin), ketorolac, or vitamin K antagonists (e.g. warfarin)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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14 participants in 1 patient group

Treatment (atorvastatin, vitamin E, pentoxifylline)

Experimental group

Description:

Patients receive atorvastatin PO QD for up to 6 weeks in the absence of disease progression or unacceptable toxicity. Beginning week 7, patients receive atorvastatin PO QD, vitamin E PO QD, and pentoxifylline PO TID for up to 12 months in the absence of disease progression or unacceptable toxicity.

Treatment:

Drug: Atorvastatin

Dietary Supplement: Vitamin E Compound

Drug: Pentoxifylline