Randomized Phase II trial of paclitaxel and carboplatin followed by gemcitabine switch-maintenance therapy versus gemcitabine and carboplatin followed by gemcitabine continuation-maintenance therapy in previously untreated advanced non-small cell lung cancer

BMC Research Notes

Ichiro Kawase⁴  Kiyoshi Komuta⁷  Isao Tachibana²  Tomoyuki Otsuka⁶  Yoshinobu Namba¹  Suguru Yamamoto⁷  Yoshitaka Ogata⁷  Takeshi Nakatani⁷  Tadashi Osaki⁵  Fumio Imamura³  Junji Uchida³  Tomonori Hirashima⁴  Kohei Okafuji⁷  Takayuki Shiroyama⁷  Takashi Kijima²  Seigo Minami⁷ 

[1] Department of Respiratory Medicine, National Hospital Organization Toneyama National Hospital, Osaka, Japan;Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka, Japan;Department of Pulmonary Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan;Department of Thoracic Malignancy, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Osaka, Japan;Department of Respiratory Medicine, Kinki Central Hospital for Mutual Aid Association of Public School Teachers, Hyogo, Japan;Department of Internal Medicine, Nishinomiya Municipal Central Hospital, Hyogo, Japan;Department of Respiratory Medicine, Osaka Police Hospital, Osaka, Japan

关键词: Randomized phase II;    Non-small cell lung cancer (NSCLC);    Continuation-maintenance;    Switch-maintenance;    Paclitaxel;    Gemcitabine;    Carboplatin;   

Others  :  1145191
DOI  :  10.1186/1756-0500-6-3

 received in 2012-08-03, accepted in 2012-12-28,  发布年份 2013

【 摘 要 】

Background

In recent years, maintenance chemotherapy is increasingly being recognized as a new treatment strategy to improve the outcome of advanced non-small cell lung cancer (NSCLC). However, the optimal maintenance strategy is still controversial. Gemcitabine is a promising candidate for single-agent maintenance therapy because of little toxicity and good tolerability. We have conducted a randomized phase II study to evaluate the validity of single-agent maintenance chemotherapy of gemcitabine and to compare continuation- and switch-maintenance.

Methods

Chemonaïve patients with stage IIIB/IV NSCLC were randomly assigned 1:1 to either arm A or B. Patients received paclitaxel (200 mg/m², day 1) plus carboplatin (AUC 6 mg/mL/min, day 1) every 3 weeks in arm A, or gemcitabine (1000 mg/m², days 1 and 8) plus carboplatin (AUC 5 mg/mL/min, day1) every 3 weeks in arm B. Non-progressive patients following 3 cycles of induction chemotherapy received maintenance gemcitabine (1000 mg/m², days 1 and 8) every 3 weeks. (Trial registration: UMIN000008252)

Results

The study was stopped because of delayed accrual at interim analysis. Of the randomly assigned 50 patients, 49 except for one in arm B were evaluable. Median progression-free survival (PFS) was 4.6 months for arm A vs. 3.5 months for arm B (HR = 1.03; 95% CI, 0.45–2.27; p = 0.95) and median overall survival (OS) was 15.0 months for arm A vs. 14.8 months for arm B (HR = 0.79; 95% CI, 0.40–1.51; p = 0.60), showing no difference between the two arms. The response rate, disease control rate, and the transit rate to maintenance phase were 36.0% (9/25), 64.0% (16/25), and 48% (12/25) for arm A vs. 16.7% (4/24), 50.0% (12/24), and 33% (8/24) for arm B, which were also statistically similar between the two arms (p = 0.13, p = 0.32, and p = 0.30, respectively). Both induction regimens were tolerable, except that more patients experienced peripheral neuropathy in arm A. Toxicities during the maintenance phase were also minimal.

Conclusion

Survival and overall response were not significantly different between the two arms. Gemcitabine may be well-tolerable and feasible for maintenance therapy.

【 授权许可】

   
2013 Minami et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Jemal A, Siegel R, Xu J, Ward E: Cancer statistics, 2010. CA Cancer J Clin 2010, 60:277-300.
• [2]Belani CP, Barstis J, Perry MC, La Rocca RV, Nattam SR, Rinaldi D, Clark R, Mills GM: Multicenter, randomized trial for stage IIIB or IV non-small-cell lung cancer using weekly paclitaxel and carboplatin followed by maintenance weekly paclitaxel or observation. J Clin Oncol 2003, 21:2933-2939.
• [3]Westeel V, Quoix E, Moro-Sibilot D, Mercier M, Breton JL, Debieuvre D, Richard P, Haller MA, Milleron B, Herman D, et al.: Randomized study of maintenance vinorelbine in responders with advanced non-small-cell lung cancer. J Natl Cancer Inst 2005, 97:499-506.
• [4]Fidias PM, Dakhil SR, Lyss AP, Loesch DM, Waterhouse DM, Bromund JL, Chen R, Hristova-Kazmierski M, Treat J, Obasaju CK, et al.: Phase III study of immediate compared with delayed docetaxel after front-line therapy with gemcitabine plus carboplatin in advanced non-small-cell lung cancer. J Clin Oncol 2009, 27:591-598.
• [5]Brodowicz T, Krzakowski M, Zwitter M, Tzekova V, Ramlau R, Ghilezan N, Ciuleanu T, Cucevic B, Gyurkovits K, Ulsperger E, et al.: Cisplatin and gemcitabine first-line chemotherapy followed by maintenance gemcitabine or best supportive care in advanced non-small cell lung cancer: a phase III trial. Lung Cancer 2006, 52:155-163.
• [6]Perol M, Chouaid C, Perol D, Barlesi F, Gervais R, Westeel V, Crequit J, Lena H, Vergnenegre A, Zalcman G, et al.: Randomized, Phase III Study of Gemcitabine or Erlotinib Maintenance Therapy Versus Observation, With Predefined Second-Line Treatment, After Cisplatin-Gemcitabine Induction Chemotherapy in Advanced Non-Small-Cell Lung Cancer. J Clin Oncol 2012, 30:3516-3524.
• [7]Ciuleanu T, Brodowicz T, Zielinski C, Kim JH, Krzakowski M, Laack E, Wu YL, Bover I, Begbie S, Tzekova V, et al.: Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet 2009, 374:1432-1440.
• [8]Takeda K, Hida T, Sato T, Ando M, Seto T, Satouchi M, Ichinose Y, Katakami N, Yamamoto N, Kudoh S, et al.: Randomized phase III trial of platinum-doublet chemotherapy followed by gefitinib compared with continued platinum-doublet chemotherapy in Japanese patients with advanced non-small-cell lung cancer: results of a west Japan thoracic oncology group trial (WJTOG0203). J Clin Oncol 2010, 28:753-760.
• [9]Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S, Szczesna A, Juhasz E, Esteban E, Molinier O, Brugger W, Melezinek I, et al.: Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol 2010, 11:521-529.
• [10]Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, Leighl N, Mezger J, Archer V, Moore N, Manegold C: Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol 2009, 27:1227-1234.
• [11]Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH: Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006, 355:2542-2550.
• [12]Le Chevalier T, Scagliotti G, Natale R, Danson S, Rosell R, Stahel R, Thomas P, Rudd RM, Vansteenkiste J, Thatcher N, et al.: Efficacy of gemcitabine plus platinum chemotherapy compared with other platinum containing regimens in advanced non-small-cell lung cancer: a meta-analysis of survival outcomes. Lung Cancer 2005, 47:69-80.
• [13]Ohe Y, Ohashi Y, Kubota K, Tamura T, Nakagawa K, Negoro S, Nishiwaki Y, Saijo N, Ariyoshi Y, Fukuoka M: 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 2007, 18:317-323.
• [14]Scagliotti GV, De Marinis F, Rinaldi M, Crino L, Gridelli C, Ricci S, Matano E, Boni C, Marangolo M, Failla G, et al.: Phase III randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer. J Clin Oncol 2002, 20:4285-4291.
• [15]Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH: Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002, 346:92-98.
• [16]Bianco V, Rozzi A, Tonini G, Santini D, Magnolfi E, Vincenzi B, D'Angelillo R, Marchei P: Gemcitabine as single agent chemotherapy in elderly patients with stages III-IV non-small cell lung cancer (NSCLC): a phase II study. Anticancer Res 2002, 22:3053-3056.
• [17]Crino L, Mosconi AM, Scagliotti G, Selvaggi G, Novello S, Rinaldi M, Della Giulia M, Gridelli C, Rossi A, Calandri C, et al.: Gemcitabine as second-line treatment for advanced non-small-cell lung cancer: A phase II trial. J Clin Oncol 1999, 17:2081-2085.
• [18]Gridelli C, Perrone F, Gallo C, Rossi A, Barletta E, Barzelloni ML, Creazzola S, Gatani T, Fiore F, Guida C, Scognamiglio F: Single-agent gemcitabine as second-line treatment in patients with advanced non small cell lung cancer (NSCLC): a phase II trial. Anticancer Res 1999, 19:4535-4538.
• [19]Zhang X, Zang J, Xu J, Bai C, Qin Y, Liu K, Wu C, Wu M, He Q, Zhang S, et al.: Maintenance therapy with continuous or switch strategy in advanced non-small cell lung cancer: a systematic review and meta-analysis. Chest 2011, 140:117-126.
• [20]Smith IE, O'Brien ME, Talbot DC, Nicolson MC, Mansi JL, Hickish TF, Norton A, Ashley S: Duration of chemotherapy in advanced non-small-cell lung cancer: a randomized trial of three versus six courses of mitomycin, vinblastine, and cisplatin. J Clin Oncol 2001, 19:1336-1343.
• [21]Belani CP, Ramalingam S, Perry MC, LaRocca RV, Rinaldi D, Gable PS, Tester WJ: Randomized, phase III study of weekly paclitaxel in combination with carboplatin versus standard every-3-weeks administration of carboplatin and paclitaxel for patients with previously untreated advanced non-small-cell lung cancer. J Clin Oncol 2008, 26:468-473.
• [22]Yamamoto N, Nakagawa K, Uejima H, Sugiura T, Takada Y, Negoro S, Matsui K, Kashii T, Takada M, Nakanishi Y, et al.: Randomized phase II study of carboplatin/gemcitabine versus vinorelbine/gemcitabine in patients with advanced nonsmall cell lung cancer: West Japan Thoracic Oncology Group (WJTOG) 0104. Cancer 2006, 107:599-605.