Vol 17, No 6 (2021)
Research paper
Published online: 2021-12-30

open access

Page views 5588
Article views/downloads 407
Get Citation

Connect on Social Media

Connect on Social Media

Which chemotherapy regimen might be the best for the second-line treatment of patients with small-cell lung cancer?

Oğuzhan Yıldız1, Mustafa Karaağaç1, Melek Karakurt Eryılmaz1, Mehmet Artaç1
Oncol Clin Pract 2021;17(6):244-252.


Introduction. Small-cell lung cancer (SCLC) is an aggressive disease. Despite the first-line (1L) chemotherapy, almost all patients need the second-line (2L) treatment within a year. However, there is no general agreement on standard 2L treatment. This study aimed to determine outcomes obtained with different treatment regimens, factors affecting the results, and standard approach in the 2L treatment of SCLC.

Material and methods. This was a singlecenter, retrospective, cross-sectional, cohort study. The inclusion criteria were age ≥ 18, histologically or cytologically proven SCLC, progressive disease after 1L treatment, and receiving 2L chemotherapy.

Results. A total of 89 patients were assessed in this study. The patients were classified into three groups: 35 patients received the combination of doxorubicin, cyclophosphamide, and vincristine (CAV), 24 patients received single-agent topotecan (TPT), and 30 patients received numerous different treatment schemes. The overall response rate (ORR), disease control rate (DCR), median progression-free survival (PFS), and median overall survival (OS) were 19.1%, 46.1%, 3.5 months, and 6.4 months, respectively. Although no statistically significant difference was found between the three groups in PFS (p = 0.195) and OS (p = 0.286), there were numerically better outcomes with CAV. In univariate analyses, the comorbidity was related to decreased PFS (p = 0.044). However, this relationship could not maintain its statistical significance in multivariate analysis (p = 0.224).

Conclusions. It is still impossible to make a standard recommendation for the 2L treatment of patients with SCLC. However, the numerical difference in favor of CAV may be clinically meaningful.

Article available in PDF format

View PDF Download PDF file


  1. Siegel R, Miller K, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019; 69(1): 7–34.
  2. Inamura K. Lung Cancer: Understanding Its Molecular Pathology and the 2015 WHO Classification. Front Oncol. 2017; 7: 193.
  3. Demedts IK, Vermaelen KY, van Meerbeeck JP. Treatment of extensive-stage small cell lung carcinoma: current status and future prospects. Eur Respir J. 2010; 35(1): 202–215.
  4. Waqar SN, Morgensztern D. Treatment advances in small cell lung cancer (SCLC). Pharmacol Ther. 2017; 180: 16–23.
  5. Farago AF, Keane FK. Current standards for clinical management of small cell lung cancer. Transl Lung Cancer Res. 2018; 7(1): 69–79.
  6. Ando M, Kobayashi K, Yoshimura A, et al. Weekly administration of irinotecan (CPT-11) plus cisplatin for refractory or relapsed small cell lung cancer. Lung Cancer. 2004; 44(1): 121–127.
  7. Groen HJ, Fokkema E, Biesma B, et al. Paclitaxel and carboplatin in the treatment of small-cell lung cancer patients resistant to cyclophosphamide, doxorubicin, and etoposide: a non-cross-resistant schedule. J Clin Oncol. 1999; 17(3): 927–932.
  8. Inoue A, Sugawara S, Yamazaki K, et al. Randomized phase II trial comparing amrubicin with topotecan in patients with previously treated small-cell lung cancer: North Japan Lung Cancer Study Group Trial 0402. J Clin Oncol. 2008; 26(33): 5401–5406.
  9. Masuda N, Fukuoka M, Kusunoki Y, et al. CPT-11: a new derivative of camptothecin for the treatment of refractory or relapsed small-cell lung cancer. J Clin Oncol. 1992; 10(8): 1225–1229.
  10. von Pawel J, Schiller JH, Shepherd FA, et al. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol. 1999; 17(2): 658–667.
  11. O'Brien MER, Ciuleanu TE, Tsekov H, et al. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol. 2006; 24(34): 5441–5447.
  12. Hurwitz JL, McCoy F, Scullin P, et al. New advances in the second-line treatment of small cell lung cancer. Oncologist. 2009; 14(10): 986–994.
  13. Bittoni MA, Arunachalam A, Li H, et al. Real-World Treatment Patterns, Overall Survival, and Occurrence and Costs of Adverse Events Associated With First-line Therapies for Medicare Patients 65 Years and Older With Advanced Non-small-cell Lung Cancer: A Retrospective Study. Clin Lung Cancer. 2018; 19(5): e629–e645.
  14. Goto K, Ohe Y, Shibata T, et al. JCOG0605 investigators. Combined chemotherapy with cisplatin, etoposide, and irinotecan versus topotecan alone as second-line treatment for patients with sensitive relapsed small-cell lung cancer (JCOG0605): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2016; 17(8): 1147–1157.
  15. Seifter EJ, Ihde DC. Therapy of small cell lung cancer: a perspective on two decades of clinical research. Semin Oncol. 1988; 15(3): 278–299.
  16. Evans WK, Osoba D, Feld R, et al. Etoposide (VP-16) and cisplatin: an effective treatment for relapse in small-cell lung cancer. J Clin Oncol. 1985; 3(1): 65–71.
  17. Sierocki JS, Hilaris BS, Hopfan S, et al. cis-Dichlorodiammineplatinum(II) and VP-16-213: an active induction regimen for small cell carcinoma of the lung. Cancer Treat Rep. 1979; 63(9-10): 1593–1597.
  18. Johnson DH. Management of small cell lung cancer: current state of the art. Chest. 1999; 116(6 Suppl): 525S–530S.
  19. Slotman BJ, van Tinteren H. Which patients with extensive stage small-cell lung cancer should and should not receive thoracic radiotherapy? Transl Lung Cancer Res. 2015; 4(3): 292–294.
  20. Byers LA, Rudin CM. Small cell lung cancer: where do we go from here? Cancer. 2015; 121(5): 664–672.
  21. Roth BJ, Johnson DH, Einhorn LH, et al. Randomized study of cyclophosphamide, doxorubicin, and vincristine versus etoposide and cisplatin versus alternation of these two regimens in extensive small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group. J Clin Oncol. 1992; 10(2): 282–291.
  22. Sculier JP, Klastersky J, Libert P, et al. A phase II study evaluating CAVi (cyclophosphamide, adriamycin, vincristine) potentiated or not by amphotericin B entrapped into sonicated liposomes, as salvage therapy for small cell lung cancer. Lung Cancer. 1990; 6(3-4): 110–118.
  23. Girling DJ. Comparison of oral etoposide and standard intravenous multidrug chemotherapy for small-cell lung cancer: a stopped multicentre randomised trial. Medical Research Council Lung Cancer Working Party. Lancet. 1996; 348(9027): 563–566.
  24. Souhami RL, Spiro SG, Rudd RM, et al. Five-day oral etoposide treatment for advanced small-cell lung cancer: randomized comparison with intravenous chemotherapy. J Natl Cancer Inst. 1997; 89(8): 577–580.
  25. Eckardt JR, von Pawel J, Pujol JL, et al. Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol. 2007; 25(15): 2086–2092.
  26. Garassino MC, Torri V, Michetti G, et al. Outcomes of small-cell lung cancer patients treated with second-line chemotherapy: a multi-institutional retrospective analysis. Lung Cancer. 2011; 72(3): 378–383.
  27. von Pawel J, Jotte R, Spigel DR, et al. Randomized phase III trial of amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer. J Clin Oncol. 2014; 32(35): 4012–4019.
  28. Li Z, Liu X, Li J, et al. [Comparison of Efficacy and Safety of Different Therapeutic Regimens as 
Second-line Treatment for Small Cell Lung Cancer]. Zhongguo Fei Ai Za Zhi. 2015; 18(5): 280–288.
  29. Zhao Y, Wan B, Zhang T, et al. Irinotecan, topotecan, paclitaxel or docetaxel for second-line treatment of small cell lung cancer: a single-center retrospective study of efficiency comparation and prognosis analysis. Transl Lung Cancer Res. 2019; 8(6): 829–837.
  30. Xing He, Zhang J, Ge F, et al. [Analysis of the Efficacy of Irinotecan in the Second-line Treatment of Refractory and Relapsed Small Cell Lung Cancer]. Zhongguo Fei Ai Za Zhi. 2021; 24(3): 167–172.
  31. Joos G, Schallier D, Pinson P, et al. Paclitaxel (PTX) as second line treatment in patients (pts) with small cell lung cancer (SCLC) refractory to carboplatin - etoposide: A multicenter phase II study. J Clin Oncol. 2004; 22(14_suppl): 7211–7211.
  32. Siu LL, Shepherd FA, Murray N, et al. Influence of age on the treatment of limited-stage small-cell lung cancer. J Clin Oncol. 1996; 14(3): 821–828.