Combination chemotherapy with intermittent erlotinib and pemetrexed for pretreated patients with advanced non-small cell lung cancer: a phase I dose-finding study

BMC Cancer

Research Article

Ryo Takahashi¹  Hiroshi Kida¹  Izumi Nagatomo¹  Isao Tachibana¹  Takashi Kijima¹  Ichiro Kawase²  Takeshi Nakatani³  Seigo Minami³  Yoshiko Takeuchi³  Masanari Hamaguchi³  Suguru Yamamoto³  Kiyoshi Komuta³ 

[1] Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, 565-0871, Osaka, Japan;Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, 565-0871, Osaka, Japan;Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, 3-7-1 Habikino, Habikino, 583-8588, Osaka, Japan;Department of Respiratory Medicine, Osaka Police Hospital, 10-31 Kitayama-cho, 543-0035, Tennoji-ku, Osaka, Japan;

关键词: Combination;    Erlotinib;    Pemetrexed;    NSCLC;    Phase I;   

DOI  :  10.1186/1471-2407-12-296

 received in 2012-01-11, accepted in 2012-06-20,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundErlotinib and pemetrexed have been approved for the second-line treatment of non-small cell lung cancer (NSCLC). These two agents have different mechanisms of action. Combined treatment with erlotinib and pemetrexed could potentially augment the antitumor activity of either agent alone. In the present study, we investigated the safety profile of combined administration of the two agents in pretreated NSCLC patients.MethodsA phase I dose-finding study (Trial registration: UMIN000002900) was performed in patients with stage III/IV nonsquamous NSCLC whose disease had progressed on or after receiving first-line chemotherapy. Patients received 500 mg/m2 of pemetrexed intravenously every 21 days and erlotinib (100 mg at Level 1 and 150 mg at Level 2) orally on days 2–16.ResultsTwelve patients, nine males and three females, were recruited. Patient characteristics included a median age of 66 years (range, 48–78 years), stage IV disease (nine cases), adenocarcinoma (seven cases) and activating mutation-positives in the epidermal growth factor receptor gene (two cases). Treatment was well-tolerated, and the recommended dose of erlotinib was fixed at 150 mg. Dose-limiting toxicities were experienced in three patients and included: grade 3 elevation of serum alanine aminotransferase, repetitive grade 4 neutropenia that required reduction of the second dose of pemetrexed and grade 3 diarrhea. No patient experienced drug-induced interstitial lung disease. Three patients achieved a partial response and stable disease was maintained in five patients.ConclusionsCombination chemotherapy of intermittent erlotinib with pemetrexed was well-tolerated, with promising efficacy against pretreated advanced nonsquamous NSCLC.

【 授权许可】

Unknown   
© Minami et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.