Japanese Journal of Clinical Oncology Advance Access published January 22, 2015 Japanese Journal of Clinical Oncology, 2015, 1–6 doi: 10.1093/jjco/hyu226 Original Article

Original Article

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A Phase II study of S-1 and irinotecan combination therapy in previously treated patients with advanced non-small cell lung cancer Shinnosuke Ikemura1, Katsuhiko Naoki1,2,*, Hiroyuki Yasuda1, Ichiro Kawada1, Satoshi Yoda1, Hideki Terai1, Takashi Sato1, Kota Ishioka1, Daisuke Arai1, Keiko Ohgino1, Hirofumi Kamata1, Jun Miyata1, Hiroki Kabata1, Tomoko Betsuyaku1, and Kenzo Soejima1 1

Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, and Cancer Center, Keio University School of Medicine, Tokyo, Japan

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*For reprints and all correspondence: Katsuhiko Naoki, Cancer Center, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. E-mail: [email protected]; [email protected] Received 5 August 2014; Accepted 21 December 2014

Abstract Objective: This Phase II study was conducted to evaluate the efficacy and safety of S-1 and irinotecan combination therapy as a second-line treatment in patients with advanced non-small cell lung cancer. Methods: Irinotecan was administered at 60 mg/m2 on Days 1 and 8. Oral S-1 was administered on Days 1–14 every 3 weeks at 80 mg/day for patients with a body surface area of 1.5 m2. The primary endpoint was response rate, while the secondary endpoints were progression-free survival, overall survival and safety. Results: Thirty-one patients were enrolled in this study. The response and disease control rates were 6.5 and 58.1%, respectively. Progression-free survival and median survival time were 2.8 and 12.6 months, respectively. Grade 3–4 adverse events were reported for 29.0% of the patients. Hematological toxicities of Grade 3 or 4 included leukopenia (9.7%), neutropenia (9.7%), febrile neutropenia (3.2%), thrombopenia (3.2%) and anemia (6.5%). Non-hematological toxicities of Grade 3 or 4 included pneumonitis (6.5%), diarrhea, colitis, dyspnea, rash, oral mucositis, anorexia and pulmonary thromboembolism/deep vein thrombosis (3.2% each). Conclusions: S-1 and irinotecan combination therapy at the present dose and schedule exhibited only modest efficacy with mild toxicities in previously treated patients with non-small cell lung cancer. No further clinical investigation with current dose and schedules is warranted for patients with non-small cell lung cancer who failed first-line platinum-based doublet chemotherapy. Key words: S-1, irinotecan, non-small-cell lung cancer, second line, Phase II trial

© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]

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S-1 plus irinotecan for pre-treated NSCLC

Patients and methods

Lung cancer is one of the leading causes of cancer related death worldwide. Non-small cell lung cancer (NSCLC) accounts for ∼85% of all cases of lung cancer (1). Most patients with NSCLC present with advanced, metastatic disease at diagnosis. Hence, the prognosis for patients with NSCLC is poor. Despite recent advances, the 5-year survival rate for patients with NSCLC is 3 months. The main exclusion criteria were active infection, a massive pleural or pericardial effusion or ascites requiring drainage, obvious interstitial pneumonia, diarrhea, intestinal paralysis or intestinal obstruction, clinically significant heart disease, other significant complications, pregnancy or lactation, active concomitant malignancy, symptomatic brain metastasis, the administration of flucytosine or atazanavir sulfate, a drug allergy or clinically significant mental disease. The study protocol was approved by the institutional review board at Keio University School of Medicine and at each institution that participated in this study. All patients provided written, witnessed and informed consent before inclusion in the study.

Study design and treatment The primary endpoint of this study was RR, and the secondary endpoints were PFS, OS and adverse events. The sample size was calculated with an α error of 0.1 and β error of 0.8. The threshold RR was 6% and estimated RR was 20%. The estimated minimum sample size was 25. Allowing for a patient ineligibility rate of 20%, we planned to enroll 30 patients. Based on the results of our Phase I study (12), we used the RD (60 mg/m2) of irinotecan combined with S-1. During each 21-day cycle, 60 mg/m2 of irinotecan was administered on Days 1 and 8. S-1 was administered twice daily from Days 1–14. The dose of S-1 was determined according to the patients’ body surface area (BSA) as follows: 80 mg/day for patients with a BSA 1.5 m2. Irinotecan (Days 1 and 8) and S-1 were administered only when the following criteria were satisfied: WBC count ≥ 3000/mm3, platelet count ≥ 100 000/mm3 and an absence of diarrhea and other non-hematological toxicities of Grade 3 or greater, excluding nausea and alopecia. The administration of irinotecan and S-1 was delayed until the criteria were satisfied up to maximum of 7 days. The dose of irinotecan in Cycle 2 was reduced by 20 mg/m2 if the WBC count was

A Phase II study of S-1 and irinotecan combination therapy in previously treated patients with advanced non-small cell lung cancer.

This Phase II study was conducted to evaluate the efficacy and safety of S-1 and irinotecan combination therapy as a second-line treatment in patients...
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