What is the optimal second-line therapy in patients with extensive stage small cell lung cancer?

From Cancer Guidelines Wiki

What is the optimal second-line therapy in patients with extensive stage small cell lung cancer?

Based on meta-analyses[1][2] second line chemotherapy provides a survival benefit in particular patients who are chemotherapy responsive and who had progressed at least three months post first-line therapy.

Phase III trials have demonstrated equivalent efficacy of topotecan (oral or IV) or CAV. However topotecan is associated with greater treatment-related toxicity (grade 4 thrombocytopenia and grade 3/4 anaemia) and oral topotecan greater diarrhoea relative to the IV formulation.[3][1]

Amrubicin in a phase II trial has demonstrated superior response rate to topotecan in chemotherapy sensitive patients with less severe neutropenia.[4] This was not borne out in a phase II trial.[5] Other agents including bortezomib,[6] histone deacetylase inhibitors,[7] and mTOR inhibitors,[8] evaluated in phase II trials have demonstrated no benefit.

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Evidence summary and recommendations

Evidence summary Level References
Second-line chemotherapy provides a survival benefit in particular patients who are chemotherapy responsive and who had progressed at least three months post first-line therapy.

Last reviewed December 2015

I [1], [2]
Topotecan (oral or IV) has equivalent efficacy relative to CAV, but differing toxicity profile. Patients treated with IV or oral topotecan suffered a reduced frequency of grade 4 neutropenia, but higher frequency of grade 4 thrombocytopenia and grade 3/4 anaemia relative to CAV.

Last reviewed December 2015

I, II [3], [1]
Evidence-based recommendationQuestion mark transparent.png Grade
Topotecan or CAV are recommended as second-line therapy in patients with extensive stage small cell lung cancer who have chemotherapy responsive disease (i.e. relapse > three months post first-line therapy).

Last reviewed December 2015

A


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References

  1. 1.0 1.1 1.2 1.3 Cheng S, Evans WK, Stys-Norman D, Shepherd FA, Lung Cancer Disease Site Group of Cancer Care Ontario's Program in Evidence-based Care. Chemotherapy for relapsed small cell lung cancer: a systematic review and practice guideline. J Thorac Oncol 2007 Apr;2(4):348-54 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17409809.
  2. 2.0 2.1 Pelayo Alvarez M, Gallego Rubio O, Bonfill Cosp X, Agra Varela Y. Chemotherapy versus best supportive care for extensive small cell lung cancer. Cochrane Database Syst Rev 2009 Oct 7;(4):CD001990 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19821287.
  3. 3.0 3.1 Eckardt JR, von Pawel J, Pujol JL, Papai Z, Quoix E, Ardizzoni A, et al. Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol 2007 May 20;25(15):2086-92 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17513814.
  4. Jotte R, Conkling P, Reynolds C, Galsky MD, Klein L, Fitzgibbons JF, et al. Randomized phase II trial of single-agent amrubicin or topotecan as second-line treatment in patients with small-cell lung cancer sensitive to first-line platinum-based chemotherapy. J Clin Oncol 2011 Jan 20;29(3):287-93 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21135284.
  5. von Pawel J, Jotte R, Spigel DR, O'Brien ME, Socinski MA, Mezger J, 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 Dec 10;32(35):4012-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25385727.
  6. Lara PN Jr, Chansky K, Davies AM, Franklin WA, Gumerlock PH, Guaglianone PP, et al. Bortezomib (PS-341) in relapsed or refractory extensive stage small cell lung cancer: a Southwest Oncology Group phase II trial (S0327). J Thorac Oncol 2006 Nov;1(9):996-1001 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17409985.
  7. Otterson GA, Hodgson L, Pang H, Vokes EE, Cancer and Leukemia Group B. Phase II study of the histone deacetylase inhibitor Romidepsin in relapsed small cell lung cancer (Cancer and Leukemia Group B 30304). J Thorac Oncol 2010 Oct;5(10):1644-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20871263.
  8. Pandya KJ, Dahlberg S, Hidalgo M, Cohen RB, Lee MW, Schiller JH, et al. A randomized, phase II trial of two dose levels of temsirolimus (CCI-779) in patients with extensive-stage small-cell lung cancer who have responding or stable disease after induction chemotherapy: a trial of the Eastern Cooperative Oncology Group (E1500). J Thorac Oncol 2007 Nov;2(11):1036-41 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17975496.

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Appendices

Further resources

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