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

o A Prospective, Randomized, Open-Label, Phase II Study Evaluating the Efficacy of Tadalafil for the Prevention of Docetaxel-Induced Peripheral Neuropathy in Patients With Metastatic Prostate Cancer

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 Overview

• Status: Completed
• Conditions: Neurotoxicity; Prostate Cancer Metastatic Disease; Chemotherapy Induced Peripheral Neuropathy (CIPN)
• Intervention / Treatment: Drug: Tadalafil 5 mg

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Neihu
    • Taipei, Neihu, Taiwan, 114
      • Tri-Service General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tadalafil Group (Experimental); Patients receive Docetaxel chemotherapy plus Tadalafil.	Drug: Tadalafil 5 mg; 5 mg administered orally on alternate days (every 48 hours), starting from the first day of chemotherapy cycle 1 until the completion of chemotherapy.
No Intervention: Control Group (No Intervention); Patients receive Docetaxel chemotherapy with standard supportive care alone.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Peripheral Neuropathy	Defined as the proportion of patients developing sensory neuropathy Grade > 1 according to NCI-CTCAE version 5.0 criteria.	From baseline up to the completion of 6 cycles of chemotherapy (approximately 12 weeks).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Moderate to Severe Neuropathy	Proportion of patients developing CTCAE Grade > 2 sensory neuropathy (limiting instrumental activities of daily living).	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.	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.	Up to 12 weeks.

Collaborators and Investigators

• Sponsor: Tri-Service General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2020
• Primary Completion (Actual): December 22, 2023
• Study Completion (Actual): August 13, 2024

Study Registration Dates

• First Submitted: December 31, 2025
• First Submitted That Met QC Criteria: December 31, 2025
• First Posted (Estimated): January 12, 2026

Study Record Updates

• Last Update Posted (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: December 31, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Prevention; Supportive Care; docetaxel; Peripheral Neuropathy; tadalafil
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Chemically-Induced Disorders; Poisoning; Peripheral Nervous System Diseases; Neurotoxicity Syndromes; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indoles; Indole Alkaloids; Heterocyclic Compounds, 3-Ring; Carbolines; Tadalafil
• Other Study ID Numbers: 2-107-05-167DIPN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No