A phase I dose-escalation study of pulsatile afatinib in patients with recurrent or progressive brain cancer.
Publication Title
Neurooncol Adv
Document Type
Article
Publication Date
1-1-2024
Keywords
california; santa monica; sjci; pacific neurosciences
Abstract
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.
Clinical Institute
Neurosciences (Brain & Spine)
Clinical Institute
Cancer
Specialty
Oncology
Specialty
Neurosciences
Specialty
Pharmacy
Recommended Citation
Juarez, Tiffany; Mini Gill, Jaya; Heng, Annie; Carrillo, Jose; Wagle, Naveed; Nomura, Natsuko; Nguyen, Minhdan; Truong, Judy D; Dobrawa, Lucia; Sivakumar, Walavan; Barkhoudarian, Garni; Kelly, Daniel F; and Kesari, Santosh, "A phase I dose-escalation study of pulsatile afatinib in patients with recurrent or progressive brain cancer." (2024). Articles, Abstracts, and Reports. 8877.
https://digitalcommons.providence.org/publications/8877