Related Experiment Video
Updated: Jul 1, 2025
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
A phase 1 study of regorafenib and sildenafil in adults with advanced solid tumors
Andrew S Poklepovic1,2, Sarah W Gordon1,2, Sejal Kothadia1,2
1Massey Cancer Center.
Abstract:
The purpose of this study is to establish the recommended phase 2 dose for regorafenib in combination with sildenafil for patients with advanced solid tumors. Secondary outcomes included identification of antitumor effects of regorafenib and sildenafil, toxicity of the combination, determination of PDE5 expression in tumor samples, and the impact of sildenafil on the pharmacokinetics of regorafenib. This study was a phase 1, open-label single-arm dose-escalation trial using a 3 + 3 design. Additional patients were enrolled at the maximum tolerated dose (MTD) until a total of 12 patients were treated at the MTD. A total of 29 patients were treated in this study. The median duration of treatment was 8 weeks. The recommended phase 2 doses determined in this study are regorafenib 160 mg daily with sildenafil 100 mg daily. The most common toxicities included palmar-plantar erythrodysesthesia syndrome (20 patients, 69%) and hypophosphatemia (18 patients, 62%). Two patients (7%) experienced grade 4 lipase increase. Objective responses were not observed; however, 14 patients (48%) had a period of stable disease during the study. Stable disease for up to 12 months was observed in patients with ovarian cancer as well as up to 20 months for a patient with cervical cancer. The combination of regorafenib and sildenafil at the recommended phase 2 dose is safe and generally well tolerated. Disease control in patients with gynecologic malignancies was especially encouraging. Further evaluation of the combination of regorafenib and sildenafil in gynecologic malignancies is warranted. Clinical Trial Registration Number: NCT02466802.
Insights
This study determined the recommended phase 2 dose for regorafenib and sildenafil in advanced solid tumors. The combination demonstrated safety and tolerability, with encouraging disease control in gynecologic malignancies.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Advanced solid tumors present significant treatment challenges.
- Regorafenib and sildenafil are agents with potential antitumor activity.
- Combination therapies are being explored to improve patient outcomes.
Purpose of the Study:
- To establish the recommended phase 2 dose (RP2D) of regorafenib in combination with sildenafil.
- To evaluate the safety and tolerability of this combination therapy.
- To explore potential antitumor effects and pharmacokinetic interactions.
Main Methods:
- Phase 1, open-label, single-arm, dose-escalation trial.
- Utilized a 3+3 design with dose escalation and expansion cohorts.
- Enrolled 29 patients with advanced solid tumors.
Main Results:
- Recommended Phase 2 Dose (RP2D): Regorafenib 160 mg daily and Sildenafil 100 mg daily.
- Most common toxicities: Palmar-plantar erythrodysesthesia syndrome (69%) and hypophosphatemia (62%).
- No objective responses observed; 48% achieved stable disease, notably in gynecologic malignancies.
Conclusions:
- The combination of regorafenib and sildenafil at the RP2D is safe and well-tolerated.
- Disease control in gynecologic malignancies warrants further investigation.
- This combination shows promise for specific patient populations.
More Related Videos
10:28Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
08:12Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
