Summary
Objectives Maintenance therapy is a standard therapeutic strategy in non-squamous non-small-cell lung cancer. However, there is no consensus regarding the benefit of maintenance therapy for patients with squamous cell lung cancer. We assessed maintenance therapy with S-1, an oral fluoropyrimidine agent, following induction therapy with carboplatin and S-1 in patients with squamous cell lung cancer. Methods In this phase II trial, chemotherapy-naïve patients with squamous cell lung cancer were enrolled to induction therapy with four cycles of carboplatin (at an area under the curve of 5 on day 1) and S-1 (80 mg/m2/day on days 1–14) in a 28-day cycle. Patients who achieved disease control after induction therapy received maintenance therapy with S-1 in a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival after administration of maintenance therapy. Results Fifty-one patients were enrolled in the study. The median progression-free survival from the start of maintenance therapy was 3.0 months (95 % confidence interval, 2.5–3.5). The most common toxicities associated with maintenance therapy were anemia, thrombocytopenia, and fatigue, but they were not severe. Conclusion S-1 maintenance therapy might be a feasible treatment option in patients with squamous cell lung cancer.
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Abbreviations
- AUC:
-
area under the curve
- CI:
-
confidence interval
- ECOG:
-
Eastern Cooperative Oncology Group
- NSCLC:
-
non-small-cell lung cancer
- PFS:
-
progression-free survival
- RECIST:
-
Response Evaluation Criteria in Solid Tumors
- UMIN:
-
University Hospital Medical Information Network
References
Fitzmaurice C, Dicker D, et al. (2013) The global burden of cancer. JAMA Oncol 1:505–527
Sawabata N, Asamura H, Goya T, Mori M, Nakanishi Y, Eguchi K, Koshiishi Y, Okumura M, Miyaoka E, Fujii Y (2012) Japanese lung cancer registry study: first prospective enrollment of a large number of surgical and nonsurgical cases in 2002. J Thorac Oncol 5:1369–1375
Meza R, Meernik C, Jeon J, Cote ML (2015) Lung cancer incidence trends by gender, race and histology in the United States, 1973-2010. PLoS One 10(3):e0121323
Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, Langer CJ, DeVore RF 3rd, Gaudreault J, Damico LA, Holmgren E, Kabbinavar F (2004) Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 22:2184–2191
Oliver TG, Patel J, Akerley W (2015) Squamous non-small cell lung cancer as a distinct clinical entity. Am J Clin Oncol 38:220–226
Scagliotti G, Hanna N, Fossella F, Sugarman K, Blatter J, Peterson P, Simms L, Shepherd FA (2009) The differential efficacy of pemetrexed according to NSCLC histology: a review of two phase III studies. Oncologist 14:253–263
Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542–2550
Kosaka T, Yatabe Y, Endoh H, Kuwano H, Takahashi T, Mitsudomi T (2004) Mutations of the epidermal growth factor receptor gene in lung cancer: biological and clinical implications. Cancer Res 64:8919–8923
Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T, North-East Japan Study G (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362:2380–2388
Owonikoko TK, Ramalingam SS, Belani CP (2010) Maintenance therapy for advanced non-small cell lung cancer: current status, controversies, and emerging consensus. Clin Cancer Res 16:2496–2504
Azzoli CG, Temin S, Aliff T, Baker, S Jr., , Brahmer J, Johnson DH, Laskin JL, Masters G, Milton D, Nordquist L, Pao W, Pfister DG, Piantadosi S, Schiller JH, Smith R, Smith TJ, Strawn JR, Trent D, Giaccone G (2011) 2011 focused update of 2009 American Society of Clinical Oncology clinical practice guideline update on chemotherapy for stage IV non-small-cell lung cancer. J Clin Oncol 29:3825–3831
Reck M, Popat S, Reinmuth N, De Ruysscher D, Kerr KM, Peters S, Group EGW (2014) Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 25(Suppl 3):iii27–iii39
Ciuleanu T, Brodowicz T, Zielinski C, Kim JH, Krzakowski M, Laack E, Wu YL, Bover I, Begbie S, Tzekova V, Cucevic B, Pereira JR, Yang SH, Madhavan J, Sugarman KP, Peterson P, John WJ, Krejcy K, Belani CP (2009) 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 374:1432–1440
Paz-Ares L, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C (2012) Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol 13:247–255
Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S, Szczesna A, Juhasz E, Esteban E, Molinier O, Brugger W, Melezinek I, Klingelschmitt G, Klughammer B, Giaccone G, investigators S (2010) Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol 11:521–529
Ichinose Y, Yoshimori K, Sakai H, Nakai Y, Sugiura T, Kawahara M, Niitani H (2004) S-1 plus cisplatin combination chemotherapy in patients with advanced non-small cell lung cancer: a multi-institutional phase II trial. Clin Cancer Res 10:7860–7864
Shiroyama T, Komuta K, Imamura F, Hirashima T, Kijima T, Tachibana I, Kawase I (2011) Phase II study of S-1 monotherapy in platinum-refractory, advanced non-small cell lung cancer. Lung Cancer 74:85–88
Okamoto I, Yoshioka H, Morita S, Ando M, Takeda K, Seto T, Yamamoto N, Saka H, Asami K, Hirashima T, Kudoh S, Satouchi M, Ikeda N, Iwamoto Y, Sawa T, Miyazaki M, Tamura K, Kurata T, Fukuoka M, Nakagawa K (2010) Phase III trial comparing oral S-1 plus carboplatin with paclitaxel plus carboplatin in chemotherapy-naive patients with advanced non-small-cell lung cancer: results of a West Japan oncology group study. J Clin Oncol 28:5240–5246
Wada M, Yamamoto M, Ryuge S, Nagashima Y, Hayashi N, Maki S, Otani S, Katono K, Takakura A, Yanaihara T, Igawa S, Yokoba M, Mitsufuji H, Kubota M, Katagiri M, Masuda N (2012) Phase II study of S-1 monotherapy in patients with previously treated, advanced non-small-cell lung cancer. Cancer Chemother Pharmacol 69:1005–1011
Charlson M, Szatrowski TP, Peterson J, Gold J (1994) Validation of a combined comorbidity index. J Clin Epidemiol 47:1245–1251
Shirasaka T, Shimamato Y, Ohshimo H, Yamaguchi M, Kato T, Yonekura K, Fukushima M (1996) Development of a novel form of an oral 5-fluorouracil derivative (S-1) directed to the potentiation of the tumor selective cytotoxicity of 5-fluorouracil by two biochemical modulators. Anti-Cancer Drugs 7:548–557
Yamada Y, Hamaguchi T, Goto M, Muro K, Matsumura Y, Shimada Y, Shirao K, Nagayama S (2003) Plasma concentrations of 5-fluorouracil and F-beta-alanine following oral administration of S-1, a dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, as compared with protracted venous infusion of 5-fluorouracil. Br J Cancer 89:816–820
Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D (2008) Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 26:3543–3551
Takiuchi H, Kawabe S, Gotoh M, Katsu K (2007) Thymidylate synthase gene expression in primary tumors predicts activity of s-1-based chemotherapy for advanced gastric cancer. Gastrointest Cancer Res 1:171–176
Kubota K, Sakai H, Katakami N, Nishio M, Inoue A, Okamoto H, Isobe H, Kunitoh H, Takiguchi Y, Kobayashi K, Nakamura Y, Ohmatsu H, Sugawara S, Minato K, Fukuda M, Yokoyama A, Takeuchi M, Michimae H, Gemma A, Kudoh S, Tokyo Cooperative Oncology G (2015) A randomized phase III trial of oral S-1 plus cisplatin versus docetaxel plus cisplatin in Japanese patients with advanced non-small-cell lung cancer: TCOG0701 CATS trial. Ann Oncol 26:1401–1408
Yoshioka H, Okamoto I, Morita S, Ando M, Takeda K, Seto T, Yamamoto N, Saka H, Atagi S, Hirashima T, Kudoh S, Satouchi M, Ikeda N, Iwamoto Y, Sawa T, Nakanishi Y, Nakagawa K (2013) Efficacy and safety analysis according to histology for S-1 in combination with carboplatin as first-line chemotherapy in patients with advanced non-small-cell lung cancer: updated results of the West Japan oncology group LETS study. Ann Oncol 24:1326–1331
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Suzuki, S., Karayama, M., Inui, N. et al. Continuation maintenance therapy with S-1 in chemotherapy-naïve patients with advanced squamous cell lung cancer. Invest New Drugs 34, 490–496 (2016). https://doi.org/10.1007/s10637-016-0365-4
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DOI: https://doi.org/10.1007/s10637-016-0365-4