o Tadalafil for Prevention of Docetaxel-Induced Peripheral Neuropathy in Prostate Cancer

Tri-Service General Hospital90 enrolled

Overview

Docetaxel is a standard chemotherapy for metastatic prostate cancer but is associated with dose-limiting peripheral neuropathy. Currently, no pharmacologic agents are established for prevention. Tadalafil, a PDE5 inhibitor, may improve microvascular perfusion and offer neuroprotection. This randomized phase II trial evaluates whether concurrent use of tadalafil (5 mg every 2 days) reduces the incidence and severity of docetaxel-induced peripheral neuropathy compared to standard care in patients with metastatic prostate cancer.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

SINGLE

Enrollment

Conditions

Prostate Cancer Metastatic Disease Chemotherapy Induced Peripheral Neuropathy (CIPN)Neurotoxicity

Interventions

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Histologically confirmed prostate adenocarcinoma. * Metastatic hormone-sensitive (mHSPC) or castration-resistant prostate cancer (mCRPC). * Scheduled to receive docetaxel chemotherapy (50 mg/m\^2 biweekly). * ECOG performance status 0-2. * Adequate bone marrow, hepatic, and renal function. Exclusion Criteria: * Pre-existing peripheral neuropathy (CTCAE grade \>= 1). * Prior treatment with taxane-based chemotherapy. * Concurrent use of nitrates or nitric oxide donors. * Severe cardiovascular disease (e.g., unstable angina, recent myocardial infarction within 6 months). * Known hypersensitivity to tadalafil or PDE5 inhibitors.

Outcomes

Primary Outcomes

Incidence of Peripheral Neuropathy

Defined as the proportion of patients developing sensory neuropathy Grade \> 1 according to NCI-CTCAE version 5.0 criteria.

Time frame: From baseline up to the completion of 6 cycles of chemotherapy (approximately 12 weeks).

Secondary Outcomes

Incidence of Moderate to Severe Neuropathy

Proportion of patients developing CTCAE Grade \> 2 sensory neuropathy (limiting instrumental activities of daily living).

Time frame: Up to 12 weeks.

Patient-Reported Neuropathy Symptoms (EORTC QLQ-CIPN20)

Change from baseline in sensory and motor scores assessed by the EORTC QLQ-CIPN20 questionnaire. Scores range from 0 to 100, with higher scores indicating worse symptoms.

Time frame: Assessed at baseline and before each chemotherapy cycle (every 2 weeks) up to 12 weeks.

Oncological Efficacy (PSA Response)

Percentage change in Prostate-Specific Antigen (PSA) levels from baseline to the end of treatment. This is a safety endpoint to ensure non-inferiority.