Cancer Chemotherapy and Pharmacology

, Volume 70, Issue 5, pp 691–697 | Cite as

Phase I/II study of S-1 combined with biweekly irinotecan chemotherapy in previously treated advanced non-small cell lung cancer

  • Hiroki Goya
  • Hiroshi Kuraishi
  • Shigeru Koyama
  • Takashi Ichiyama
  • Fumiaki Yoshiike
  • Kazuya Hirai
  • Toshihiko Agatsuma
  • Kazunari Tateishi
  • Shintaro Kanda
  • Hiroshi Yamamoto
  • Keishi Kubo
  • Tomonobu Koizumi
Original Article
First Online:
Received:
Accepted:

Abstract

Purpose

This phase I/II study was designed to evaluate a combination of irinotecan and S-1 a new regimen for salvage chemotherapy in patients with advanced or metastatic non-small cell lung cancer (NSCLC).

Methods

The study group comprised patients with advanced or metastatic NSCLC who had previously received at least one platinum-containing chemotherapy. Patients received irinotecan on days 1, 15 and oral S-1 (40 mg/m2 twice daily as a fixed dose) on day 1 to 14 of a 28-day cycle.

Results

In the phase I part, irinotecan was given in escalating doses of 70 (Level 1), 80 (Level 2), and 90 mg/m2 (Level 3). Three of the 5 patients given Level 3 had dose-limiting toxicity, and Level 2 (80 mg/m2 of irinotecan) was designated as the recommended dose. In phase II, 38 patients received a median of 7.4 cycles of irinotecan at the recommended dose. The overall response rate was 15.8 % (90 % confidence interval (CI): 6.1–25.5 %), and the median progression-free and overall survival times were 4.5 months (95 % CI: 3.5–5.0) and 15.0 months (95 % CI: 9.5–20.6) months, respectively. Toxicity was generally mild. Grade 3 or higher toxicity included neutropenia in 17.9 % of the patients, thrombocytopenia in 5.1 % and nausea in 7.7 %.

Conclusion

Combination chemotherapy with S-1 and irinotecan was considered an effective salvage regimen in patients with advanced or metastatic NSCLC.

Keywords

Chemo-refractory Salvage chemotherapy Second line CTP-11 
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Notes

Acknowledgments

We thank the patients and their families for their support and participation in this study.

Conflict of interest

We declare that we have no conflict of interest in relation to this study.

References

  1. 1.
    Matsuda T, Marugame T, Kamo KI, Katanoda K, Ajiki W, Sobue T (2011) The Japan Cancer Surveillance Research Group. Cancer Incidence and Incidence Rates in Japan in 2005: based on Data from 12 Population-based Cancer Registries in the Monitoring of Cancer Incidence in Japan (MCIJ) Project. Jpn J Clin Oncol 41:139–147PubMedCrossRefGoogle Scholar
  2. 2.
    Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62:10–29PubMedCrossRefGoogle Scholar
  3. 3.
    Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH (2002) Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 346:92–98PubMedCrossRefGoogle Scholar
  4. 4.
    Ohe Y, Ohashi Y, Kubota K, Tamura T, Nakagawa K, Negoro S, Nishiwaki Y, Saijo N, Ariyoshi Y, Fukuoka M (2007) Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: four-Arm Cooperative Study in Japan. Ann Oncol 18:317–323PubMedCrossRefGoogle Scholar
  5. 5.
    Gridelli C, Ardizzoni A, Ciardiello F, Hanna N, Heymach JV, Perrone F, Rosell R, Shepherd FA, Thatcher N, Vansteenkiste J, De Petris L, Di Maio M, De Marinis F (2008) Second-line treatment of advanced non-small cell lung cancer. J Thorac Oncol 3:430–440PubMedCrossRefGoogle Scholar
  6. 6.
    Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabárbara P, Seymour L, National Cancer Institute of Canada Clinical Trials Group (2005) Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 353:123–132PubMedCrossRefGoogle Scholar
  7. 7.
    Lee DH, Park K, Kim JH, Lee JS, Shin SW, Kang JH, Ahn MJ, Ahn JS, Suh C, Kim SW (2010) Randomized Phase III trial of gefitinib versus docetaxel in non-small cell lung cancer patients who have previously received platinum-based chemotherapy. Clin Cancer Res 16:1307–1314PubMedCrossRefGoogle Scholar
  8. 8.
    Shirasaka T, Nakano K, Takechi T, Satake H, Uchida J, Fujioka A, Saito H, Okabe H, Oyama K, Takeda S, Unemi N, Fukushima M (1996) Antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1) against human colon carcinoma orthotopically implanted into nude rats. Cancer Res 56:2602–2606PubMedGoogle Scholar
  9. 9.
    Takechi T, Nakano K, Uchida J, Mita A, Toko K, Takeda S, Unemi N, Shirasaka T (1997) Antitumor activity and low intestinal toxicity of S-1, a new formulation of oral tegafur, in experimental tumor models in rats. Cancer Chemother Pharmacol 39:205–211PubMedCrossRefGoogle Scholar
  10. 10.
    Koizumi W, Kurihara M, Nakano S, Hasegawa K (2000) Phase II study of S-1, a novel oral derivative of 5-fluorouracil, in advanced gastric cancer. For the S-1 Cooperative Gastric Cancer Study Group. Oncology 58:191–197PubMedCrossRefGoogle Scholar
  11. 11.
    Kawahara M, Furuse K, Segawa Y, Yoshimori K, Matsui K, Kudoh S, Hasegawa K, Niitani H (2001) S-1 Cooperative Study Group (Lung Cancer Working Group). Phase II study of S-1, a novel oral fluorouracil, in advanced non-small-cell lung cancer. Br J Cancer 85:939–943PubMedCrossRefGoogle Scholar
  12. 12.
    Nishiyama O, Taniguchi H, Kondoh Y, Takada K, Baba K, Saito H, Sugino Y, Yamamoto M, Ogasawara T, Kondo M, Imaizumi K, Hasegawa Y, Suzuki R, Shimokata K (2011) Central Japan Lung Study Group. Phase II study of S-1 monotherapy as a first-line treatment for elderly patients with advanced nonsmall-cell lung cancer: the Central Japan Lung Study Group trial 0404. Anticancer Drugs 22:811–816PubMedCrossRefGoogle Scholar
  13. 13.
    Ichinose Y, Yoshimori K, Sakai H, Nakai Y, Sugiura T, Kawahara M, Niitani H (2004) S-1 plus cisplatin combination chemotherapy in patients with advanced non-small cell lung cancer: a multi-institutional phase II trial. Clin Cancer Res 10:7860–7864PubMedCrossRefGoogle Scholar
  14. 14.
    Fukuoka M, Niitani H, Suzuki A et al (1992) A phase II study of CPT-11, a new derivative of camptothecin, for previously untreated non-small-cell lung cancer. J Clin Oncol 10:16–20PubMedGoogle Scholar
  15. 15.
    Nagano T, Yasunaga M, Goto K, Kenmotsu H, Koga Y, Kuroda J, Nishimura Y, Sugino T, Nishiwaki Y, Matsumura Y (2010) Synergistic antitumor activity of the SN-38-incorporating polymeric micelles NK012 with S-1 in a mouse model of non-small cell lung cancer. Int J Cancer 127:2699–2706PubMedCrossRefGoogle Scholar
  16. 16.
    Houghton JA, Cheshire PJ, Hallman JD 2nd, Lutz L, Luo X, Li Y, Houghton PJ (1996) Evaluation of irinotecan in combination with 5-fluorouracil or etoposide in xenograft models of colon adenocarcinoma and rhabdomyosarcoma. Clin Cancer Res 2:107–118PubMedGoogle Scholar
  17. 17.
    Takiuchi H, Narahara H, Tsujinaka T, Gotoh M, Kawabe S, Katsu K, Iishi H, Tatsuta M, Fujitani K, Furukawa H, Taguchi T (2005) Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG)Phase I study of S-1 combined with irinotecan (CPT-11) in patients with advanced gastric cancer (OGSG 0002). Jpn J Clin Oncol 35:520–525PubMedCrossRefGoogle Scholar
  18. 18.
    Vanhoefer U, Harstrick A, Achterrath W, Cao S, Seeber S, Rustum YM (2001) Irinotecan in the treatment of colorectal cancer: clinical overview. J Clin Oncol 19:1501–1518PubMedGoogle Scholar
  19. 19.
    Inokuchi M, Yamashita T, Yamada H, Kojima K, Ichikawa W, Nihei Z, Kawano T, Sugihara K (2006) Phase I/II study of S-1 combined with irinotecan for metastatic advanced gastric cancer. Br J Cancer 94:1130–1135PubMedCrossRefGoogle Scholar
  20. 20.
    Muro K, Boku N, Shimada Y et al (2010) Irinotecan plus S-1 (IRIS) versus fluorouracil and folinic acid plus irinotecan (FOLFIRI) as second-line chemotherapy for metastatic colorectal cancer: a randomised phase 2/3 non-inferiority study (FIRIS study). Lancet Oncol 11:853–860PubMedCrossRefGoogle Scholar
  21. 21.
    Goto A, Yamada Y, Yasui H, Kato K, Hamaguchi T, Muro K, Shimada Y, Shirao K (2006) Phase II study of combination therapy with S-1 and irinotecan in patients with advanced colorectal cancer. Ann Oncol 17:968–973PubMedCrossRefGoogle Scholar
  22. 22.
    Ishimoto O, Ishida T, Honda Y, Munakata M, Sugawara S (2009) Phase I study of daily S-1 combined with weekly irinotecan in patients with advanced non-small cell lung cancer. Int J Clin Oncol 14:43–47PubMedCrossRefGoogle Scholar
  23. 23.
    Yoda S, Soejima K, Yasuda H, Naoki K, Kawada I, Watanabe H, Nakachi I, Satomi R, Nakayama S, Ikemura S, Terai H, Sato T, Morosawa M, Asano K (2011) A phase I study of S-1 and irinotecan combination therapy in previously treated advanced non-small cell lung cancer patients. Cancer Chemother Pharmacol 67:717–722PubMedCrossRefGoogle Scholar
  24. 24.
    Okamoto I, Nishimura T, Miyazaki M, Yoshioka H, Kubo A, Takeda K, Ebi N, Sugawara S, Katakami N, Fukuoka M, Nakagawa K (2008) Phase II study of combination therapy with S-1 and irinotecan for advanced non-small cell lung cancer: west Japan thoracic oncology group 3505. Clin Cancer Res 14:5250–5254PubMedCrossRefGoogle Scholar
  25. 25.
    Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216PubMedCrossRefGoogle Scholar
  26. 26.
    Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 [National Cancer Institute Web site]. May 22, 2003. Available at: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. Accessed March 1, 2011
  27. 27.
    Di Maio M, Chiodini P, Georgoulias V, Hatzidaki D, Takeda K, Wachters FM, Gebbia V, Smit EF, Morabito A, Gallo C, Perrone F, Gridelli C (2009) Meta-analysis of single-agent chemotherapy compared with combination chemotherapy as second-line treatment of advanced non-small-cell lung cancer. J Clin Oncol 27:1836–1843PubMedCrossRefGoogle Scholar
  28. 28.
    Park SR, Kong SY, Rhee J, Park YI, Ryu KW, Lee JH, Kim YW, Choi IJ, Kim CG, Lee JY, Cho SJ, Kim NK (2011) Phase II study of a triplet regimen of S-1 combined with irinotecan and oxaliplatin in patients with metastatic gastric cancer: clinical and pharmacogenetic results. Ann Oncol 22:890–896PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Hiroki Goya
    • 1
    • 3
  • Hiroshi Kuraishi
    • 1
  • Shigeru Koyama
    • 1
  • Takashi Ichiyama
    • 2
    • 3
  • Fumiaki Yoshiike
    • 2
  • Kazuya Hirai
    • 2
  • Toshihiko Agatsuma
    • 3
  • Kazunari Tateishi
    • 3
  • Shintaro Kanda
    • 3
  • Hiroshi Yamamoto
    • 3
  • Keishi Kubo
    • 3
  • Tomonobu Koizumi
    • 4
  1. 1.Respiratory DivisionNagano Red Cross HospitalNaganoJapan
  2. 2.Respiratory DivisionNagano Municipal HospitalNaganoJapan
  3. 3.First Department of Internal MedicineShinshu University School of MedicineMatsumotoJapan
  4. 4.Division of Clinical Oncology, Comprehensive Cancer CenterShinshu University Hospital School of MedicineMatsumotoJapan

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