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. 2005 Aug 31;95(8):691–695. doi: 10.1111/j.1349-7006.2004.tb03331.x

Phase I study of cisplatin, vinorelbine, and concurrent thoracic radiotherapy for unresectable stage III non‐small cell lung cancer

Ikuo Sekine 1,✉, Kazumasa Noda 3, Fumihiro Oshita 3, Kouzou Yamada 3, Manabu Tanaka 3, Kosuke Yamashita 4, Hiroshi Nokihara 1, Noboru Yamamoto 1, Hideo Kunitoh 1, Yuichiro Ohe 1, Tomohide Tamura 1, Tetsuro Kodama 1, Minako Sumi 2, Nagahiro Saijo 1
PMCID: PMC11160088  PMID: 15298734

Abstract

To determine the recommended phase II dose of vinorelbine in combination with cisplatin and thoracic radiotherapy (TRT) in patients with unresectable stage III non‐small cell lung cancer (NSCLC), 18 patients received cisplatin (80 μg/m2) on day 1 and vinorelbine (20 μg/m2 in level 1, and 25 μg/m2 in level 2) on days 1 and 8 every 4 weeks for 4 cycles. TRT consisted of a single dose of 2 Gy once daily for 3 weeks followed by a rest of 4 days, and then the same TRT for 3 weeks to a total dose of 60 Gy. Fifteen (83%) patients received 60 Gy of TRT and 14 (78%) patients received 4 cycles of chemotherapy. Ten (77%) of 13 patients at level 1 and all 5 patients at level 2 developed grade 3‐4 neutro‐penia. Four (31%) patients at level 1 and 3 (60%) patients at level 2 developed grade 3‐4 infection. None developed ≥grade 3 esophagitis or lung toxicity. Dose‐limiting toxicity was noted in 33% of the patients in level 1 and in 60% of the patients in level 2. The overall response rate (95% confidence interval) was 83% (59–96%) with 15 partial responses. The median survival time was 30.4 months, and the 1‐year, 2‐year, and 3‐year survival rates were 72%, 61%, and 50%, respectively. In conclusion, the recommended dose is the level 1 dose, and this regimen is feasible and promising in patients with stage III NSCLC.

References

  • 1. Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest 1997; 111: 1710–7. [DOI] [PubMed] [Google Scholar]
  • 2. Jett JR, Scott WJ, Rivera MP, Sause, WT and American College of Chest Physicians . Guidelines on treatment of stage IIIB non‐small cell lung cancer. Chest 2003; 123: 221S–5S. [DOI] [PubMed] [Google Scholar]
  • 3. Pierre F, Maurice P, Gilles R, Pascal T, Pierre‐Jean S, Hervé L, Alain V, Jean‐Yves D, Francoise M, Fancoise M. A randomized phase III trial of sequential chemoradiotherapy in locally advanced non‐small‐cell lung cancer. Proc Am. Soc Clin Oncol 2001; 20: 312a (abstr 1246). [Google Scholar]
  • 4. Curren W Jr, Scott C, Langer C, Komaki R, Lee J, Hauser S, Movsas B, Wasserman TH, Rosenthal S, Byhardt R, Sause W, Cox J. Phase III comparison of sequential vs concurrent chemoradiation for patients with unresectable stage III non‐small‐cell lung cancer (NSCLC): initial report of the Radiation Therapy Oncology Group (RTOG) 9410. Proc Am. Soc Clin Oncol 2000; 19: 484a (abstr 1891). [Google Scholar]
  • 5. Furuse K, Fukuoka M, Kawahara M, Nishikawa H, Takada Y, Kudoh S, Katagami N, Ariyoshi Y. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non‐small‐cell lung cancer. J Clin Oncol 1999; 17: 2692–9. [DOI] [PubMed] [Google Scholar]
  • 6. Kubota K, Tamura T, Fukuoka M, Furuse K, Ikegami H, Ariyoshi Y, Kurita Y, Saijo N. Phase II study of concurrent chemotherapy and radiotherapy for unresectable stage III non‐small‐cell lung cancer: long‐term follow‐up results. Japan Clinical Oncology Group Protocol 8902. Ann Oncol 2000; 11: 445–50. [DOI] [PubMed] [Google Scholar]
  • 7. Furuse K, Kubota K, Kawahara M, Kodama N, Ogawara M, Akira M, Nakajima S, Takada M, Kusunoki Y, Negoro S, Matsui K, Masuda N, Takifuji N, Kudoh S, Nishioka M, Fukuoka M. Phase II study of concurrent radiotherapy and chemotherapy for unresectable stage III non‐small‐cell lung cancer. Southern Osaka Lung Cancer Study Group. J Clin. Oncol 1995; 3: 869–75. [DOI] [PubMed] [Google Scholar]
  • 8. Atagi S, Kawahara M, Hosoe S, Ogawara M, Kawaguchi T, Okishio K, Naka N, Sunami T, Mitsuoka S, Akira M. A phase II study of continuous concurrent thoracic radiotherapy in combination with mitomycin, vindesine and cisplatin in unresectable stage III non‐small cell lung cancer. Lung Cancer 2002; 36: 105–11. [DOI] [PubMed] [Google Scholar]
  • 9. Sekine I, Saijo N. Novel combination chemotherapy in the treatment of non‐small cell lung cancer. Exp Opin Pharmacother 2000; 1: 1131–61. [DOI] [PubMed] [Google Scholar]
  • 10. Furuse K, Fukuoka M, Kuba M, Yamori S, Nakai Y, Negoro S, Katagami N, Takada Y, Kinuwaki E, Kawahara M, Kubota K, Sakuma A, Niitani H. Randomized study of vinorelbine (VRB) versus vindesine (YDS) in previously untreated stage IIIB or IV non‐small‐cell lung cancer (NSCLC). The Japan Vinorelbine Lung Cancer Cooperative Study Group. Ann. Oncol 1996; 7: 815–20. [DOI] [PubMed] [Google Scholar]
  • 11. Le Chevalier T, Brisgand D, Douillard JY, Pujol JL, Alberola V, Monnier A, Riviere A, Lianes P, Chomy P, Cigolari S, Gottfried M, Ruffle P, Panizo A, Gaspard MH, Ravaioli A, Besenval M, Besson F, Martinez A, Berthaud P, Tursz T. Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non‐small‐cell lung cancer: results of a European multicenter trial including 612 patients. J Clin. Oncol 1994; 12: 360–7. [DOI] [PubMed] [Google Scholar]
  • 12. Perol M, Guerin JC, Thomas P, Poirier R, Carles P, Robinet G, Kleisbauer JP, Paillotin D, Vergnenegre A, Balmes P, Touron D, Grivaux M, Pham E. Multicenter randomized trial comparing cisplatin‐mitomycin‐vinorelbine versus cisplatin‐mitomycin‐vindesine in advanced non‐small cell lung cancer. ‘Groupe Francais de Pneumo‐Cancerologie.’ Lung Cancer 1996; 14: 119–34. [DOI] [PubMed] [Google Scholar]
  • 13. Kawahara M, Furuse K, Nishiwaki Y, Horai T, Saijo N, Hasegawa K, Ohashi Y, Niitani H. Randomized study of vinorelbine (VRB) or vindesine (VDS) with cisplatin (C) and mitomycin (M) as induction chemotherapy in stage IIIB or IV non‐small cell lung cancer (NSCLC)‐final results. Proc Am Soc Clin. Oncol 2000; 19: 489a (abstr 1914). [Google Scholar]
  • 14. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbonne PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am. J Clin. Oncol 1982; 5: 649–55. [PubMed] [Google Scholar]
  • 15. JCOG Administrational Committee: National Cancer Institute‐Common Toxicity Criteria (NCI‐CTC Version 2.0, Jan 30, 1998). Japanese edition by JCOG. Available at http://www.med.gunma‐u.ac.jp/event/CTCJ_v20.pdf.
  • 16. WHO . Handbook for reporting results of cancer treatment. WHO Offset Publication no. 48. Geneva : World Health Organization; 1979. [Google Scholar]
  • 17. Armitage P, Berry G. Survival analysis. In: Statistical methods in medical research. 3rd ed. Oxford : Blackwell Sci Publ; 1994. p. 469–92. [Google Scholar]
  • 18. Sekine I, Matsuda T, Saisho T, Watanabe H, Yamamoto N, Kunitoh H, Ohe Y, Tamura T, Kodama T, Saijo N. Bacterial meningitis observed in a phase I trial of vinorelbine, cisplatin and thoracic radiotherapy for non‐small cell lung cancer: report of a case and discussion on dose‐limiting toxicity. Jpn J Clin. Oncol 2000; 30: 401–5. [DOI] [PubMed] [Google Scholar]
  • 19. Masters GA, Haraf DJ, Hoffman PC, Drinkard LC, Krauss SA, Ferguson MK, Olak J, Samuels BL, Golomb HM, Vokes EE. Phase I study of vinorelbine, cisplatin, and concomitant thoracic radiation in the treatment of advanced chest malignancies. J Clin Oncol 1998; 16: 2157–63. [DOI] [PubMed] [Google Scholar]
  • 20. Vokes EE, Herndon JE 2nd, Crawford J, Leopold KA, Perry MC, Mikker AA, Green MR. Randomized phase II study of cisplatin with gemcitabine or paclitaxel or vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy for stage IIIB non‐small‐cell lung cancer: cancer and leukemia group B study 9431. J Clin. Oncol 2002; 20: 4191–8. [DOI] [PubMed] [Google Scholar]
  • 21. Zatloukal P, Petruzelka L, Zemanova M, Krejbich F, Havel L. Vinorelbine (VRL) plus cisplatin (CDDP) and concurrent radiotherapy in advanced non‐small cell lung cancer. Proc Am. Soc Clin Oncol 1998; 17: 505a (abstr 1947). [Google Scholar]
  • 22. Alcedo J, Gallardo D, Lopez‐Mariscal A, Calderillo G, Green L, Correa E, Zamora J, Mohar A. Cisplatin/vinorelbine (CDDP/VNR) and radiotherapy (XRT) in advanced non‐small cell lung cancer (ANSCLC): an effective and feasible option with no need for dose reduction. Proc Am. Soc Clin Oncol 1999; 18: 494a (abstr 1905). [Google Scholar]
  • 23. Hotta K, Sekine I, Tamura T, Sawada M, Watanabe H, Kusaba H, Akiyama Y, Inoue A, Shimoyama T, Nokihara H, Ueda Y, Yamamoto N, Kunitoh H, Ohe Y, Kodama T, Saijo N. A phase I/II study of cisplatin and vinorelbine chemotherapy in patients with advanced non‐small cell lung cancer. Jpn. J Clin Oncol 2001; 31: 596–600. [DOI] [PubMed] [Google Scholar]

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