title: Phase II trial of carboplatin, S-1, and gefitinib as first-line triplet chemotherapy for advanced non-small cell lung cancer patients with activating epidermal growth factor receptor mutations.
abstract: Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is an effective treatment for advanced non-small cell lung cancer (NSCLC) in patients with activating EGFR mutations. However, there have been little evidence-based studies of gefitinib in combination with platinum-doublet therapy in these patients. We performed a phase II trial to determine the efficacy and safety of triplet chemotherapy with gefitinib, carboplatin, and S-1 as a first-line treatment. This was a multicentre, single-arm, phase II trial of carboplatin, S-1, and gefitinib in advanced NSCLC patients with activating EGFR mutations. Patients received four courses of these drugs in 3-4 week cycles. In each cycle, carboplatin (area under curve = 5) was administered on day 1, S-1 (80 mg/m(2)) on days 1-14, and gefitinib (250 mg) every day. Subsequently, the same regimen without carboplatin was administered until disease progression or unacceptable toxicity occurred. The 1-year progression-free survival (PFS) was the primary endpoint, while response rate (RR), PFS, overall survival (OS), and safety were secondary endpoints. Thirty-five patients were enrolled into this study. The 1-year PFS was 74.3% and the overall RR was 85.7%. The median PFS for all patients was 17.6 months (95% confidence interval 15.5-∞), but the median OS was not reached, because 28 patients were still alive after a median follow-up time of 21.4 months. Haematological adverse events (grade 3 or higher) included neutropaenia (17.1%), thrombocytopenia (14.3%), and anaemia (5.7%), while non-haematological adverse events (grade 3 or higher) included elevated aminotransferase (20.0%), diarrhoea (14.3%), and febrile neutropaenia (2.9%). No interstitial lung disease or treatment-related deaths occurred. Combination chemotherapy with carboplatin, S-1, and gefitinib is efficacious and well tolerated as a first-line treatment in advanced NSCLC patients with activating EGFR mutations.
authors.affiliation: Department of Internal Medicine, Kinki-Chuo Chest Medical Center, Osaka, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tamiya
authors.forename: Motohiro
authors.initials: M
authors.lastname: Tamiya
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shiroyama
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Saijo
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakatani
authors.forename: Shojiro
authors.initials: S
authors.lastname: Minomo
authors.forename: Taisuke
authors.initials: T
authors.lastname: Tsuji
authors.forename: Naoko
authors.initials: N
authors.lastname: Takeuchi
authors.forename: Naoki
authors.initials: N
authors.lastname: Omachi
authors.forename: Kanako
authors.initials: K
authors.lastname: Kurata
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Norio
authors.initials: N
authors.lastname: Okamoto
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Okishio
authors.forename: Tomonori
authors.initials: T
authors.lastname: Hirashima
authors.forename: Shinji
authors.initials: S
authors.lastname: Atagi
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D004338:Drug Combinations; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010094:Oxonic Acid / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D005641:Tegafur / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D011799:Quinazolines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D016190:Carboplatin; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib