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01.04.2012 | Original Article

Phase I study of continuous afatinib (BIBW 2992) in patients with advanced non-small cell lung cancer after prior chemotherapy/erlotinib/gefitinib (LUX-Lung 4)

verfasst von: H. Murakami, T. Tamura, T. Takahashi, H. Nokihara, T. Naito, Y. Nakamura, K. Nishio, Y. Seki, A. Sarashina, M. Shahidi, N. Yamamoto

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 4/2012

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Abstract

Purpose

This Phase I study determined the maximum-tolerated dose (MTD) of afatinib (Afatinib is an investigational compound and its safety and efficacy have not yet been established) (BIBW 2992; trade name not yet approved by FDA), an irreversible inhibitor of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor (HER)1 and 2, up to a dose of 50 mg/day in advanced non-small cell lung cancer (NSCLC), to establish the recommended dose for Phase II.

Methods

Patients with advanced NSCLC who had received prior platinum-doublet chemotherapy and/or erlotinib/gefitinib therapy, or who were ineligible for, or not amenable to, treatment with established therapies, received oral afatinib once daily. The MTD was determined based on dose-limiting toxicities (DLTs); other assessments included safety, pharmacokinetic profile, antitumour activity according to response evaluation criteria in solid tumours and EGFR/HER1 mutation analysis where possible.

Results

Twelve evaluable patients were treated at doses of 20–50 mg/day. One DLT was observed at 50 mg/day in Course 1 (Grade 3 mucositis). The most frequent drug-related adverse events were diarrhoea, dry skin, stomatitis, rash, paronychia and anorexia; most were Grade 1 or 2. Six out of 12 patients had tumour size reductions; durable stable disease was achieved in three patients including one with EGFR/HER1 exon 19 and T790 M mutations. Peak plasma concentrations of afatinib were reached 3–4 h after administration and declined with a half-life of 30–40 h. Afatinib 50 mg/day was well tolerated with an acceptable safety profile during Phase I.

Conclusion

Recommended dose for Phase II was defined as 50 mg/day for Japanese patients; the same as for non-Japanese patients.

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Titel: Phase I study of continuous afatinib (BIBW 2992) in patients with advanced non-small cell lung cancer after prior chemotherapy/erlotinib/gefitinib (LUX-Lung 4)
verfasst von: H. Murakami
T. Tamura
T. Takahashi
H. Nokihara
T. Naito
Y. Nakamura
K. Nishio
Y. Seki
A. Sarashina
M. Shahidi
N. Yamamoto
Publikationsdatum: 01.04.2012
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 4/2012
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-011-1738-1

Neu im Fachgebiet Onkologie

25.04.2024 | Nierenkarzinom | Nachrichten

Springer Medizin

Phase I study of continuous afatinib (BIBW 2992) in patients with advanced non-small cell lung cancer after prior chemotherapy/erlotinib/gefitinib (LUX-Lung 4)

Abstract

Purpose

Methods

Results

Conclusion

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Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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