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BMC Cancer. 2012; 12: 296.
Published online Jul 18, 2012. doi:  10.1186/1471-2407-12-296
PMCID: PMC3437193
Combination chemotherapy with intermittent erlotinib and pemetrexed for pretreated patients with advanced non-small cell lung cancer: a phase I dose-finding study
Seigo Minami,1 Takashi Kijima,corresponding author2 Ryo Takahashi,2 Hiroshi Kida,2 Takeshi Nakatani,1 Masanari Hamaguchi,1 Yoshiko Takeuchi,1 Izumi Nagatomo,2 Suguru Yamamoto,1 Isao Tachibana,2 Kiyoshi Komuta,1 and Ichiro Kawase2,3
1Department of Respiratory Medicine, Osaka Police Hospital, 10-31 Kitayama-cho, Tennoji-ku, Osaka 543-0035, Japan
2Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
3Present Affiliation: Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, 3-7-1 Habikino, Habikino, Osaka 583-8588, Japan
corresponding authorCorresponding author.
Seigo Minami: seigominami/at/yahoo.co.jp; Takashi Kijima: tkijima/at/imed3.med.osaka-u.ac.jp; Ryo Takahashi: tryo/at/imed3.med.osaka-u.ac.jp; Hiroshi Kida: hiroshi.kida/at/imed3.med.osaka-u.ac.jp; Takeshi Nakatani: nakatanitakeshi64/at/yahoo.co.jp; Masanari Hamaguchi: masanari_hamaguchi/at/yahoo.co.jp; Yoshiko Takeuchi: reed_bamboo/at/hotmail.com; Izumi Nagatomo: iznagatomo/at/imed3.med.osaka-u.ac.jp; Suguru Yamamoto: sugu-run/at/oph.gr.jp; Isao Tachibana: itachi02/at/imed3.med.osaka-u.ac.jp; Kiyoshi Komuta: komuta1954/at/song.ocn.ne.jp; Ichiro Kawase: kawasei/at/opho.jp
Received January 11, 2012; Accepted June 20, 2012.
Abstract
Background
Erlotinib 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.
Methods
A 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.
Results
Twelve 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.
Conclusions
Combination chemotherapy of intermittent erlotinib with pemetrexed was well-tolerated, with promising efficacy against pretreated advanced nonsquamous NSCLC.
Keywords: Combination, Erlotinib, Pemetrexed, NSCLC, Phase I
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