Phase II study of adjuvant vinorelbine and cisplatin in Japanese patients with completely resected stage II and III non-small cell lung cancer
Adjuvant vinorelbine and cisplatin chemotherapy is recognized as a standard regimen for patients with completely resected stage II and III non-small cell lung cancer (NSCLC). However, efficacy of adjuvant chemotherapy in Japanese phase III trials with cisplatin-containing regimen has been controversial, and data are limited on the long-term outcome of adjuvant vinorelbine and cisplatin chemotherapy for NSCLC patients.
This was a single-arm phase II study in patients with completely resected pathological stage II or III NSCLC, who had not received prior chemotherapy or radiotherapy. Patients received 4 cycles of vinorelbine [25 mg/m2 of body surface area (BSA)] and cisplatin (40 mg/m2 of BSA) on days 1 and 8, every 4 weeks. Primary end point was the 3-year relapse-free survival; secondary end points were overall survival and safety.
Between December 2006 and January 2011, 60 patients (40 men and 20 women, median age 64 years) were enrolled; all patients were evaluable for survival and safety. Three-year relapse-free survival rate was 55.0 % (95 % confidence interval 42.4–67.6 %). Three- and five-year overall survival rates were 83.3 and 77.8 %, respectively. There were no chemotherapy-related deaths, and adverse effects were acceptable.
Adjuvant vinorelbine and cisplatin chemotherapy was safe and showed a valid relapse-free survival rate. This regimen could be used as a standard regimen and deserves to be a control arm of trials on adjuvant chemotherapy in the Japanese NSCLC patient population.
KeywordsNon-small cell lung cancer Adjuvant chemotherapy Cisplatin Vinorelbine
- 1.Sawabata N, Miyaoka E, Asamura H, Nakanishi Y, Eguchi K, Mori M, Nomori H, Fujii Y, Okumura M, Yokoi K (2011) Japanese Joint Committee for Lung Cancer Registration. Japanese lung cancer registry study of 11,663 surgical cases in 2004: demographic and prognosis changes over decade. J Thorac Oncol 6:1229–1235PubMedCrossRefGoogle Scholar
- 3.Scagliotti GV, Fossati R, Torri V, Crinò L, Giaccone G, Silvano G, Martelli M, Clerici M, Cognetti F, Tonato M, Adjuvant Lung Project Italy/European Organisation for Research Treatment of Cancer-Lung Cancer Cooperative Group Investigators (2003) Randomized study of adjuvant chemotherapy for completely resected stage I, II, or IIIA non-small-cell lung cancer. J Natl Cancer Inst 95:1453–1461PubMedCrossRefGoogle Scholar
- 4.Spiro SG, Rudd RM, Souhami RL, Brown J, Fairlamb DJ, Gower NH, Maslove L, Milroy R, Napp V, Parmar MK, Peake MD, Stephens RJ, Thorpe H, Waller DA, West P, Big Lung Trial Participants (2004) Chemotherapy versus supportive care in advanced non-small cell lung cancer: improved survival without detriment to quality of life. Thorax 59:828–836PubMedCentralPubMedCrossRefGoogle Scholar
- 5.Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J, International Adjuvant Lung Cancer Trial Collaborative Group (2004) Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 350:351–360PubMedCrossRefGoogle Scholar
- 6.Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, Cormier Y, Goss G, Inculet R, Vallieres E, Fry W, Bethune D, Ayoub J, Ding K, Seymour L, Graham B, Tsao MS, Gandara D, Kesler K, Demmy T, Shepherd F, National Cancer Institute of Canada Clinical Trials Group, National Cancer Institute of the United States Intergroup JBR.10 Trial Investigators (2005) Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med 352:2589–2597PubMedCrossRefGoogle Scholar
- 7.Douillard JY, Rosell R, De Lena M, Carpagnano F, Ramlau R, Gonzáles-Larriba JL, Grodzki T, Pereira JR, Le Groumellec A, Lorusso V, Clary C, Torres AJ, Dahabreh J, Souquet PJ, Astudillo J, Fournel P, Artal-Cortes A, Jassem J, Koubkova L, His P, Riggi M, Hurteloup P (2006) Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB–IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol 7:719–727PubMedCrossRefGoogle Scholar
- 8.Pignon JP, Tribodet H, Scagliotti GV, Douillard JY, Shepherd FA, Stephens RJ, Dunant A, Torri V, Rosell R, Seymour L, Spiro SG, Rolland E, Fossati R, Aubert D, Ding K, Waller D, Le Chevalier T (2008) LACE Collaborative Group. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol 26:3552–3559PubMedCrossRefGoogle Scholar
- 9.Douillard JY, Tribodet H, Aubert D, Shepherd FA, Rosell R, Ding K, Veillard AS, Seymour L, Le Chevalier T, Spiro S, Stephens R, Pignon JP, LACE Collaborative Group (2010) Adjuvant cisplatin and vinorelbine for completely resected non-small cell lung cancer: subgroup analysis of the lung adjuvant cisplatin evaluation. J Thorac Oncol 5:220–228PubMedCrossRefGoogle Scholar
- 10.) The Japan Lung Cancer Society (2013) http://www.haigan.gr.jp/modules/guideline/index.php?content_id=3. Accessed 19 Mar 2014
- 13.Sonobe M, Date H, Wada H, Okubo K, Hamakawa H, Teramukai S, Matsumura A, Nakagawa T, Sumitomo S, Miyamoto Y, Okumura N, Takeo S, Kawakami K, Aoki M, Kosaka S (2013) The Japan-multinational trial organization. Prognostic factors after complete resection of pN2 non-small cell lung cancer. J Thorac Cardiovasc Surg 146:788–795PubMedCrossRefGoogle Scholar
- 15.Shigematsu H, Lin L, Takahashi T, Nomura M, Suzuki M, Wistuba II, Fong KM, Lee H, Toyooka S, Shimizu N, Fujisawa T, Feng Z, Roth JA, Herz J, Minna JD, Gazdar AF (2005) Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst 97:339–346PubMedCrossRefGoogle Scholar
- 17.Sonobe M, Nakagawa M, Takenaka K, Katakura H, Adachi M, Yanagihara K, Otake Y, Wada H, Tanaka F (2007) Influence of epidermal growth factor receptor (EGFR) gene mutations on the expression of EGFR, phosphoryl-Akt, and phosphoryl-MAPK, and on the prognosis of patients with non-small cell lung cancer. J Surg Oncol 95:63–69PubMedCrossRefGoogle Scholar
- 18.Sonobe M, Kobayashi M, Ishikawa M, Kikuchi R, Nakayama E, Takahashi T, Menju T, Takenaka K, Miyahara R, Huang CL, Okubo K, Bando T, Date H (2012) Impact of KRAS and EGFR gene mutations on recurrence and survival in patients with surgically resected lung adenocarcinomas. Ann Surg Oncol 19(Suppl 3):S347–S354PubMedCrossRefGoogle Scholar
- 19.Shukuya T, Takahashi T, Tamiya A, Ono A, Igawa S, Tsuya A, Nakamura Y, Murakami H, Naito T, Kaira K, Endo M, Yamamoto N (2009) Evaluation of the safety and compliance of 3-week cycles of vinorelbine on days 1 and 8 and cisplatin on day 1 as adjuvant chemotherapy in Japanese patients with completely resected pathological stage IB to IIIA non-small cell lung cancer: a retrospective study. Jpn J Clin Oncol 39:158–162PubMedCrossRefGoogle Scholar
- 20.Kenmotsu H, Ohde Y, Shukuya T, Eida H, Akamatsu H, Ono A, Nakamura Y, Tsuya A, Kaira K, Naito T, Murakami H, Takahashi T, Maniwa T, Isaka M, Endo M, Kondo H, Yamamoto N (2012) Feasibility of postoperative adjuvant chemotherapy of cisplatin plus vinorelbine for completely resected non-small-cell lung cancer: a retrospective study in Japan. Respir Investig 50:157–161PubMedCrossRefGoogle Scholar
- 22.Vallières E, Shepherd FA, Crowley J, Van Houtte P, Postmus PE, Carney D, Chansky K, Shaikh Z, Goldstraw P (2009) International Association for the Study of Lung Cancer International Staging Committee and Participating Institutions. The IASLC Lung Cancer Staging Project: proposals regarding the relevance of TNM in the pathologic staging of small cell lung cancer in the forthcoming (seventh) edition of the TNM classification for lung cancer. J Thorac Oncol 4:1049–1059PubMedCrossRefGoogle Scholar
- 24.Hirai F, Seto T, Shimokawa M, Inamasu E, Toyozawa R, Toyokawa G, Yoshida T, Shiraishi Y, Takenaka T, Yamaguchi M, Takenoyama M, Ichinose Y (2014) Split-dose cisplatin and vinorelbine as adjuvant chemotherapy for completely resected non-small cell lung cancer. Anticancer Res 34:927–931PubMedGoogle Scholar