Abstract
The aim of the study is to evaluate the efficacy and safety of a three-drug chemotherapy regimen including gemcitabine, carboplatin, and paclitaxel as induction therapy in clinical stage III non-small cell lung cancer (NSCLC). Patients aged 18–75 years, ECOG PS 0–1, with unresectable clinical stage IIIA or IIIB NSCLC suitable for definitive radiation treatment, were treated in a phase II study with i.v. carboplatin AUC 5 and i.v., paclitaxel 175 mg/m2 on day 1, and i.v. gemcitabine 800 mg/m2 on days 1 and 8, every 3 weeks for 3 cycles, as previously assessed in a dose-finding study. Primary end point was overall response rate (ORR). Secondary end points included: toxicity, progression-free survival (PFS), resection rate, and overall survival (OS). Out of the 60 enrolled patients, 49 were males and 11 females, 31 patients had stage IIIA and 29 stage IIIB NSCLC. Forty-four partial responses and one complete response were observed, for an ORR of 75 %. The most frequent G3–G4 toxicity included: neutropenia (in 23 % of cases), hypertransaminasemia (12 %), and diarrhea (5 %). With a median follow-up of 15 months (range 2–72), median PFS was 10.5 months (95 % CI 9.9–11.4) and median OS was 21.1 months (95 % CI 19.7–22.8). Fourteen stage IIIA patients underwent surgery, for a resection rate of 45 %. A median PFS of 17.8 months (95 % CI 16.2–19.7) and a median OS of 25.5 months (95 % CI 23.0–28.4) were observed in stage IIIA patients. The three-drug chemotherapy regimen, at the employed dose, demonstrated a considerable disease response and resection rate, with acceptable toxicity.
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References
Spira A, Ettinger DS. Multidisciplinary management of lung cancer. N Engl J Med. 2004;350:379–92.
Pfister DG, Johnson DH, Azzoli CG, et al. American Society of Clinical. Oncology treatment of unresectable non-small-cell lung cancer guidelines: update 2003. J Clin Oncol. 2004;22:330–53.
Furuse K, Fukuoka M, Kawakara M, et al. 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.
Curran WJ Jr, Paulus R, Langer CJ, et al. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011;103:1452–60.
Fournel P, Robinet G, Thomas P, et al. Randomized phase III trial of sequential chemoradiotherapy compared with concurrent chemoradiotherapy in locally advanced non-small-cell lung cancer: groupe Lyon-Saint-Etienne d’Oncologie Thoracique-Groupe Français de Pneumo-Cancérologie NPC 95–01 Study. J Clin Oncol. 2005;23:5910–7.
Zatloukal P, Petruzelka I, Zemanova M, et al. Concurrent versus sequential chemoradiotherapy with cisplatin and vinorelbine in locally advanced non-small cell lung cancer: a randomized study. Lung Cancer. 2004;46:87–98.
Rowell NP, O’rourke NP. Concurrent chemoradiotherapy in non-small cell lung cancer. Cochrane Database Syst Rev. 2004;18:CD002140.
Le Chevalier T, Scagliotti G, Natale R, 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.
Paccagnella A, Oniga F, Bearz A, et al. Adding gemcitabine to paclitaxel/carboplatin increases survival in advanced non-small-cell lung cancer: results of a phase II–III study. J Clin Oncol. 2006;24:681–7.
Abratt RP, Lee JS, Han JY, et al. Phase II trial of gemcitabine-carboplatin- paclitaxel as neoadjuvant chemotherapy for operable non-small-cell lung cancer. J Thorac Oncol. 2006;1:135–40.
Schallier D, Neyns B, Fontaine CA, et al. A novel triplet regimen with paclitaxel, carboplatin and gemcitabine (PACCAGE) as induction chemotherapy for locally advanced unresectable non small cell lung cancer (NSCLC). Lung Cancer. 2007;56:247–54.
Novello G, Banna GL, Restuccia N, et al. Induction chemotherapy with carboplatin (C), paclitaxel (P) and gemcitabine (G) in unresectable stage IIIA or IIIB non-small cell lung cancer (NSCLC). A phase I-II study. Proc Am Soc Clin Oncol; J Clin Oncol. 2008;26:7592.
Mountain CF. Revisions in the international system for staging lung cancer. Chest. 1997;111:1710–7.
Ratain MJ, Eckhardt SG. Phase II studies of modern drugs directed against new targets: if you are fazed, too, then resist RECIST. J Clin Oncol. 2004;22:4442–5.
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81.
Simon R. Confidence intervals for reporting results of clinical trials. Ann Intern Med. 1986;105:429–35.
Vinh-Hung V. Power of test comparing independent proportions. Comput Biol Med. 1986;16:39–43.
Cox DR. Regression models and life tables. JR Stat Soc (B). 1972;34:187.
Schallier D, Bral S, Ilsen B, Neyns B, Fontaine C, Decoster L, De Mey J, Meysman M, De Greve J. Final overall results of a study with a novel triplet induction chemotherapy regimen (PACCAGE) followed by consolidation radiotherapy in locally advanced inoperable non-small cell lung cancer (NSCLC). J Thorac Oncol. 2009;4:728–35.
Goldstraw P, Crowley J, Chansky K, et al. The IASLC lung cancer staging project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol. 2007;2:706–14.
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Banna, G.L., Lipari, H., Nicolosi, M. et al. A three-drug induction chemotherapy with gemcitabine, carboplatin, and paclitaxel for stage III non-small cell lung cancer. Med Oncol 30, 533 (2013). https://doi.org/10.1007/s12032-013-0533-8
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DOI: https://doi.org/10.1007/s12032-013-0533-8