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A phase I dose-escalation study of pulsatile afatinib in patients with recurrent or progressive brain cancer.
Juarez, Tiffany M; Gill, Jaya M; Heng, Annie; Carrillo, Jose A; Wagle, Naveed; Nomura, Natsuko; Nguyen, Minhdan; Truong, Judy; Dobrawa, Lucia; Sivakumar, Walavan; Barkhoudarian, Garni; Kelly, Daniel F; Kesari, Santosh.
Afiliação
  • Juarez TM; Pacific Neuroscience Institute and Saint John's Cancer Institute at Providence Saint John's Health Center, Neuro-Oncology, Santa Monica, California, USA.
  • Gill JM; Pacific Neuroscience Institute and Saint John's Cancer Institute at Providence Saint John's Health Center, Neuro-Oncology, Santa Monica, California, USA.
  • Heng A; Pacific Neuroscience Institute and Saint John's Cancer Institute at Providence Saint John's Health Center, Neuro-Oncology, Santa Monica, California, USA.
  • Carrillo JA; Pacific Neuroscience Institute and Saint John's Cancer Institute at Providence Saint John's Health Center, Neuro-Oncology, Santa Monica, California, USA.
  • Wagle N; Pacific Neuroscience Institute and Saint John's Cancer Institute at Providence Saint John's Health Center, Neuro-Oncology, Santa Monica, California, USA.
  • Nomura N; Pacific Neuroscience Institute and Saint John's Cancer Institute at Providence Saint John's Health Center, Neuro-Oncology, Santa Monica, California, USA.
  • Nguyen M; Pacific Neuroscience Institute and Saint John's Cancer Institute at Providence Saint John's Health Center, Neuro-Oncology, Santa Monica, California, USA.
  • Truong J; Pacific Neuroscience Institute and Saint John's Cancer Institute at Providence Saint John's Health Center, Neuro-Oncology, Santa Monica, California, USA.
  • Dobrawa L; Pacific Neuroscience Institute and Saint John's Cancer Institute at Providence Saint John's Health Center, Neuro-Oncology, Santa Monica, California, USA.
  • Sivakumar W; Pacific Neuroscience Institute and Saint John's Cancer Institute at Providence Saint John's Health Center, Neurosurgery, Santa Monica, California, USA.
  • Barkhoudarian G; Pacific Neuroscience Institute and Saint John's Cancer Institute at Providence Saint John's Health Center, Neurosurgery, Santa Monica, California, USA.
  • Kelly DF; Pacific Neuroscience Institute and Saint John's Cancer Institute at Providence Saint John's Health Center, Neurosurgery, Santa Monica, California, USA.
  • Kesari S; Pacific Neuroscience Institute and Saint John's Cancer Institute at Providence Saint John's Health Center, Neuro-Oncology, Santa Monica, California, USA.
Neurooncol Adv ; 6(1): vdae049, 2024.
Article em En | MEDLINE | ID: mdl-38680990
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Neurooncol Adv Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Neurooncol Adv Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido