Related Experiment Video
Updated: May 7, 2026
A Simple Guide Screw Method for Intracranial Xenograft Studies in Mice
Published on: September 26, 2011
A phase I dose-escalation study of pulsatile afatinib in patients with recurrent or progressive brain cancer
Tiffany M Juarez1, Jaya M Gill1, Annie Heng1
1Pacific Neuroscience Institute and Saint John's Cancer Institute at Providence Saint John's Health Center, Neuro-Oncology, Santa Monica, California, USA.
Background:
Afatinib (BIBW2992; Gilotrif®) is a selective and irreversible inhibitor of the epidermal growth factor receptor (ErbB; EGFR) family. It inhibits EGFR, HER2, and HER4 phosphorylation, resulting in tumor growth inhibition and regression. This phase I dose-escalation trial of pulsatile afatinib examined the safety, drug penetration into the central nervous system, preliminary antitumor activity, and recommended phase II dose in patients with progressive or recurrent brain cancers.
Methods:
Afatinib was taken orally once every 4 days or once every 7 days depending on dose cohort, until disease progression or unacceptable toxicity.
Results:
A total of 24 patients received the investigational agent and were evaluable for safety analyses, and 21 patients were evaluable for efficacy. Dosing was administered at 80 mg every 4 days, 120 mg every 4 days, 180 mg every 4 days, or 280 mg every 7 days. A recommended phase II dose of pulsatile afatinib was established at 280 mg every 7 days as there were no dose-limiting toxicities in any of the dosing cohorts and all toxicities were deemed manageable. The most common drug-related toxicities were diarrhea, rash, nausea, vomiting, fatigue, stomatitis, pruritus, and limb edema. Out of the 21 patients evaluable for efficacy, 2 patients (9.5%) exhibited partial response based on Response Assessment in Neuro-Oncology criteria and disease stabilization was seen in 3 patients (14.3%).
Conclusions:
Afatinib taken orally was safe and well-tolerated up to 280 mg every 7 days in brain cancer patients.
Insights
Pulsatile afatinib is safe and well-tolerated for brain cancer patients at a dose of 280 mg every 7 days. This regimen showed manageable toxicities and preliminary antitumor activity in a phase I trial.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Afatinib is a selective, irreversible inhibitor of the epidermal growth factor receptor (EGFR) family, targeting EGFR, HER2, and HER4.
- It demonstrates tumor growth inhibition and regression by blocking phosphorylation of key signaling proteins.
- This study focused on brain cancers, a challenging area for targeted therapies due to the blood-brain barrier.
Purpose of the Study:
- To evaluate the safety and tolerability of pulsatile afatinib in patients with progressive or recurrent brain cancers.
- To assess central nervous system (CNS) drug penetration of afatinib.
- To determine the recommended phase II dose (RP2D) and preliminary antitumor activity.
Main Methods:
- A phase I, dose-escalation trial involving oral administration of pulsatile afatinib.
- Dosing cohorts included 80 mg every 4 days, 120 mg every 4 days, 180 mg every 4 days, and 280 mg every 7 days.
- Patients were evaluated for safety, CNS penetration, and efficacy until disease progression or unacceptable toxicity.
Main Results:
- Twenty-four patients were evaluable for safety, and 21 for efficacy.
- The recommended phase II dose was established at 280 mg every 7 days, with no dose-limiting toxicities observed.
- Common toxicities included diarrhea, rash, and nausea; 9.5% of patients achieved partial response and 14.3% had disease stabilization.
Conclusions:
- Pulsatile afatinib administered orally is safe and well-tolerated in brain cancer patients at doses up to 280 mg every 7 days.
- The established RP2D of 280 mg every 7 days supports further investigation in phase II trials.
- Afatinib demonstrates potential for managing progressive or recurrent brain cancers.
More Related Videos
06:15Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
09:38Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
