Adjuvant Chemotherapy of Gemcitabine plus Carboplatin versus Paclitaxel plus Carboplatin in Patients with Resected Non-Small Cell Lung Cancer

Takanori Ayabe, Masaki Tomita, Kunihide Nakamura

Department of Surgery II, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.

DOI: 10.4236/jct.2013.48A003                

Abstract

Background: This retrospective study was to evaluate the efficacy and toxicity of gemcitabine plus carboplatin (GC regimen) and paclitaxel plus carboplatin (PC regimen) combination chemotherapy administered as an adjuvant therapy after complete resection of non-small cell lung cancer. Methods: Forty-four patients (GC regimen, n = 29; PC regimen, n = 15) received gemcitabine at a dose of 1000 mg/m² on days 1 and 8, and carboplatin with the target dose of area under the curve (AUC) of 4 on day 8 every 28 days and paclitaxel at a dose of 70 mg/m² on days 1, 8 and 15, and carboplatin with the target dose of AUC of 5 on day 1 every 28 days. Results: A total of 130 cycles of the treatment were administered (averaged, 3.1 in GC arm and 2.7 cycles in PC arm). Forty-three patients (97.7%) completed the scheduled cycles. One patient (2.3%) was discontinued due to grade 4 pneumonia. The dose was reduced in 2 patients (4.5%) due to grade 4 thrombocytopenia. Grade 3/4 neutropenia was significantly observed in the PC group (GC: 12/29, 41.4%; PC: 11/15, 73.3%, p = 0.0443). The nonhematological toxicities were mild. Grade 1/2 alanine aminotransferase and aspartate aminotransferase in the GC group was significantly observed higher compared to those of the PC group (GC: 20/29, 69.0%; PC: 4/15, 26.7%, p = 0.0076). Grade 1/2 alopecia was significantly observed in the PC group (GC: 0/25, 0.0%; PC: 13/15, 86.7%, p < 0.0001). There was no treatment-related death. The median survival time (MST) of the entire GC group was 784 days, the 3-year overall survival (OS) was 75.9%, and 3-year recurrence-free survival (RFS) was 65.5%. The MST of the entire PC group was 963 days, the 3-year OS was 80.0%, and the 3-year RFS was 60.0%. Conclusion: These results demonstrate that the GC and PC combination chemotherapies are efficacious and feasible regimens, which should be considered as one of the standard therapies for adjuvant therapy.

Keywords

Non-Small Cell Lung Cancer; Gemcitabine; Paclitaxel; Carboplatin; Combination Chemotherapy; Adjuvant Therapy

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	A. Jemal, T. Murray, E. Ward, A. Samuels, R. C. Tiwari, A. Ghafoor, E. J. Feuer and M. J. Thun, “Cancer Statistics, 2005,” CA: A Cancer Journal for Clinicians, Vol. 55, No. 1, 2005, pp. 10-30. doi:10.3322/canjclin.55.1.10
[2]	C. F. Mountain, “Revisions in the International System for Staging Lung Cancer,” Chest, Vol. 111, No. 6, 1997, pp. 1710-1717. doi:10.1378/chest.111.6.1710
[3]	T. Goya, H. Asamura, H. Yoshimur, H. Kato, K. Shimokata, R. Tsuchiya, Y. Sohara, T. Miya and E. Miyaoka (Japanese Joint Committee of Lung Cancer Registry), “Prognosis of 6644 Resected Non-Small Cell Lung Cancers in Japan: A Japanese Lung Cancer Registry Study,” Lung Cancer, Vol. 50, No. 2, 2005, pp. 227-234. doi:10.1016/j.lungcan.2005.05.021
[4]	Non-Small Cell Lung Cancer Collaborative Group, “Chemotherapy in Non-Small Cell Lung Cancer: A MetaAnalysis Using Updated Data on Individual Patients from 52 Randomised Clinical Trials,” BMJ, Vol. 311, No. 7010, 1995, pp. 899-909. doi:10.1136/bmj.311.7010.899
[5]	S. M. Keller, S. Adak, H. Wagner, A. Herskovic, R. Komaki, B. J. Brooks, M. C. Perry, R. B. Livingston and D. H. Johnson, “A Randomized Trial of Postoperative Adjuvant Therapy in Patients with Completely Resected Stage II or IIIA Non-Small-Cell Lung Cancer. Eastern Cooperative Oncology Group,” The New England Journal of Medicine, Vol. 343, No. 17, 2000, pp. 1217-1222. doi:10.1056/NEJM200010263431703
[6]	Y. Ichinose, H. Tada, T. Koike, N. Nishizawa, R. Tsuchiya, K. Nagai, et al., “A Randomized Phase III Trial of Postoperative Adjuvant Chemotherapy in Patients with Completely Resected Stage IIIA-N2 Non-Small Cell Lung Cancer: Japan Clinical Oncology Group (JCOG) 9304 Trial,” Proceeding of ASCO 2001, Vol. 20, 2001, Article ID: A1241.
[7]	G. V. Scagliotti, R. Fossati, V. Torri, L. Crinò, G. Giaccone, G. Silvano, M. Martelli, M. Clerici, F. Cognetti and M. Tonato (Adjuvant Lung Project Italy/European Organisation for Research Treatment of Cancer-Lung Cancer Cooperative Group Investigators), “Randomized Study of Adjuvant Chemotherapy for Completely Resected Stage I, II, or IIIA Non-Small-Cell Lung Cancer,” Journal of the National Cancer Institute, Vol. 95, No. 19, 2003, pp. 1453-1461. doi:10.1093/jnci/djg059
[8]	D. Waller, D. J. Fairlamb, N. Gower, R. Milroy, M. D. Peake, R. M. Rudd, et al., “The Big Lung Trial (BLT): Determining the Value of Cisplatin-Based Chemotherapy for All Patients with Non-Small Cell Lung Cancer (NSCLC). Preliminary Results in the Surgical Setting,” Proceeding of ASCO 2003, Vol. 22, 2003, Article ID: A2543.
[9]	R. Arriagada, B. Bergman, A. Dunant, T. Le Chevalier, J. P. Pignon and J. Vansteenkiste (International Adjuvant Lung Cancer Trial Collaborative Group), “CisplatinBased Chemotherapy in Patients with Completely Resected Non-Small Cell Lung Cancer,” The New England Journal of Medicine, Vol. 350, No. 2, 2004, pp. 351-360.
[10]	L. H. Sobin and I. D. Fleming, “TNM Classification of Malignant Tumors, Fifth Edition (1997). Union Internationale Contre le Cancer and the American Joint Committee on Cancer,” Cancer, Vol. 80, No. 9, 1997, pp. 1803-1804.
[11]	W. D. Travis, K. Garg, W. A. Franklin, I. I. Wistuba, B. Sabloff, M. Noguchi, R. Kakinuma, M. Zakowski, M. Ginsberg, R. Padera, et al., “Bronchioloalveolar Carcinoma and Lung Adenocarcinoma: The Clinical Importance and Research Relevance of the 2004 World Health Organization Pathologic Criteria,” Journal of Thoracic Oncology, Vol. 1, No. 9, 2006, pp. S13-S19. doi:10.1097/01243894-200611001-00004
[12]	A. H. Calvert, D. R. Newell, L. A. Gumbrell, S. O’Reilly, M. Burnell, F. E. Boxall, Z. H. Siddik, I. R. Judson, M. E. Gore and E. Wiltshaw, “Carboplatin Dosage: Prospective Evaluation of a Simple Formula Based on Renal Function,” Journal of Clinical Oncology, Vol. 7, No. 11, 1989, pp. 1748-1756.
[13]	D. W. Cockcroft and M. H. Gault, “Prediction of Creatinine Clearance from Serum Creatinine,” Nephron, Vol. 16, No. 1, 1976, pp. 31-41.
[14]	E. L. Kaplan and P. Meier, “Non-Parametric Estimation from Incomplete Observations,” Journal of the American Statistical Association, Vol. 53, 1958, pp. 457-481. doi:10.1080/01621459.1958.10501452
[15]	R. Arriagada, B. Bergman, A. Dunant, T. Le Chevalier, J. P. Pignon and J. Vansteenkiste (International Adjuvant Lung Cancer Trial Collaborative Group), “Cisplatin-Based Adjuvant Chemotherapy in Patients with Completely Resected Non-Small-Cell Lung Cancer,” The New England Journal of Medicine, Vol. 350, No. 4, 2004, pp. 351-360. doi:10.1056/NEJMoa031644
[16]	T. Winton, R. Livingston, D. Johnson, J. Rigas, M. Johnston, C. Butts, Y. Cormier, G. Goss, R. Inculet, E. Vallieres, et al., “National Cancer Institute of Canada Clinical Trials Group; National Cancer Institute of the United States Intergroup JBR.10 Trial Investigators. Vinorelbine plus Cisplatin vs. Observation in Resected NonSmall-Cell Lung Cancer,” The New England Journal of Medicine, Vol. 352, No. 25, 2005, pp. 2589-2597. doi:10.1056/NEJMoa043623
[17]	J. Y. Douillard, R. Rosell, M. De Lena, F. Carpagnano, R. Ramlau, J. L. Gonzáles-Larriba, T. Grodzki, J. R. Pereira, A. Le Groumellec, V. Lorusso, et al., “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 Oncology, Vol. 7, No. 9, 2006, pp. 719-727. doi:10.1016/S1470-2045(06)70804-X
[18]	J. P. Pignon, H. Tribodet, G. V. Scagliotti, J. Y. Douillard, F. A. Shepherd, R. J. Stephens, A. Dunant, V. Torri, R. Rosell, L. Seymour, et al., “LACE Collaborative Group. Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE Collaborative Group,” Journal of Clinical Oncology, Vol. 26, No. 21, 2008, pp. 3552-3559. doi:10.1200/JCO.2007.13.9030
[19]	H. Kato, Y. Ichinose, M. Ohta, E. Hata, N. Tsubota, H. Tada, Y. Watanabe, H. Wada, M. Tsuboi, N. Hamajima, et al., “Japan Lung Cancer Research Group on Postsurgical Adjuvant Chemotherapy. A Randomized Trial of Adjuvant Chemotherapy with Uracil-Tegafur for Adenocarcinoma of the Lung,” The New England Journal of Medicine, Vol. 350, No. 17, 2004, pp. 1713-1721. doi:10.1056/NEJMoa032792
[20]	NSCLC Meta-Analyses Collaborative Group, R. Arriagada, A. Auperin, S. Burdett, J. P. Higgins, D. H. Johnson, T. Le Chevalier, C. Le Pechoux, M. K. Parmar, J. P. Pignon, R. L. Souhami, et al., “Adjuvant Chemotherapy, with or without Postoperative Radiotherapy, in Operable Non-Small-Cell Lung Cancer: Two Meta-Analyses of Individual Patient Data,” Lancet, Vol. 375, No. 9722, 2010, pp. 1267-1277. doi:10.1016/S0140-6736(10)60059-1
[21]	Y. Ohe, Y. Ohashi, K. Kubota, T. Tamura, K. Nakagawa, S. Negoro, Y. Nishiwaki, N. Saijo, Y. Ariyoshi and M. Fukuoka, “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,” Annals of Oncology, Vol. 18, No. 2, 2007, pp. 317-323. doi:10.1093/annonc/mdl377
[22]	P. Zatloukal, L. Petruzelka, M. Zemanová, V. Kolek, J. Skricková, M. Pesek, H. Fojt?, I. Grygárková, D. Sixtová, J. Roubec, et al., “Gemcitabine plus Cisplatin vs. Gemcitabine plus Carboplatin in Stage IIIb and IV Non-Small Cell Lung Cancer: A Phase III Randomized Trial,” Lung Cancer, Vol. 41, No. 3, 2003, pp. 321-331. doi:10.1016/S0169-5002(03)00233-2
[23]	P. Rocchi, C. Mattioli,. M. B. Rocchi, R. Mattioli, P. Lippe, R. Trivisonne, F. Buzzi, G. De Signoribus, G. Tuveri, G. Rossi, et al., “Randomized, Multicenter, Phase II Study of Gemcitabine plus Cisplatin versus Gemcitabine plus Carboplatin in Patients with Advanced Non-Small Cell Lung Cancer,” Lung Cancer, Vol. 41, No. 1, 2003, pp. 81-89. doi:10.1016/S0169-5002(03)00140-5
[24]	K. Kelly, J. Crowley, P. A. Bunn Jr., C. A. Presant, P. K., Grevstad, C. M. Moinpour, S. D. Ramsey, A. J. Wozniak, G. R. Weiss, D. F. Moore, et al., “Randomized Phase III Trial of Paclitaxel plus Carboplatin versus Vinorelbine plus Cisplatin in the Treatment of Patients with Advanced Non-Small-Cell Lung Cancer: A Southwest Oncology Group Trial,” Journal of Clinical Oncology, Vol. 19, No. 13, 2001, pp. 3210-3218.
[25]	M. Hirabayashi, K. Endoh, M. Teramachi, M. Okuda, K. Yamaguchi, K. Fukuda, H. Tokuhisa, H. Kagioka, N. Nakai and M. Nakade, “Phase II Study of Carboplatin and Weekly Paclitaxel Combination Chemotherapy in Advanced Non-Small Cell Lung Cancer: A Kansai Clinical Oncology Group Study,” Lung Cancer, Vol. 44, No. 3, 2004, pp. 355-362. doi:10.1016/j.lungcan.2003.12.001