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Small Cell Lung Cancer Treatment Protocols 

  • Author: Marvaretta M Stevenson, MD; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
 
Updated: Feb 29, 2016
 
 

Treatment Protocols

Treatment protocols for small cell lung cancer (SCLC) are provided below, including first-line therapy, therapy for limited-stage disease, and therapy for extensive-stage disease.

Treatment recommendations for limited-stage SCLC

Stages I-III disease:

  • Limited-stage disease is typically treated with a combination of chemotherapy and radiation (concurrently)[1]
  • Sequential therapy can also be given for limited-stage disease for patients unable to tolerate concurrent chemoradiation; chemotherapy is given first, followed by radiation therapy because of the high rate of responsiveness to chemotherapy for SCLC[2, 1]
  • T3-4 tumors due to multiple ipsilateral lung nodules are treated as extensive-stage disease[1]

Concurrent chemotherapy recommendationswith radiation for limited-stage diseaseinclude the following:

  • Cisplatin 60 mg/m2 IV on day 1 plus etoposide 120 mg/m2 IV on days 1-3 every 21d for 4 cycles[3] or
  • Cisplatin 80 mg/m2 IV on day 1 plus  etoposide 100 mg/m2 IV on days 1-3 every 28d for 4 cycles[4]
  • Carboplatin AUC 5-6 IV day 1 plus  etoposide 100 mg/m2 IV days 1-3 every 21d[5]
  • Radiotherapy for limited-stage disease should start with cycle 1 or 2 of chemotherapy

Chemotherapy recommendations for patients not able to tolerate concurrent chemotherapy and radiation:

  • Patients with limited-stage (stages I–III) disease who are not able to tolerate chemotherapy and radiation concurrently should be treated with chemotherapy as first-line therapy
  • Cisplatin 60-80 mg/m2 IV on day 1 plus  etoposide 80-120 mg/m2 IV on days 1-3 every 21-28d (maximum of 4 cycles)[3, 4] or
  • Carboplatin AUC 5-6 IV on day 1 plus  etoposide 80-100 mg/m2 IV on days 1-3 every 28d (maximum of 4 cycles)[6] (see also the Carboplatin AUC Dose Calculation [Calvert formula] calculator)

First-line chemotherapy for extensive-stage disease

Stage IV disease:

  • The following treatment recommendations should be given for a maximum of 4-6 cycles:
  • Cisplatin 60-80 mg/m2 IV on day 1 plus  etoposide 80-120 mg/m2 IV on days 1-3 every 21-28d[7, 8, 9, 10, 11, 12, 13, 14] or
  • Carboplatin AUC 5-6 IV on day 1 plus  etoposide 80-100 mg/m2 IV on days 1-3 every 28d[14, 15, 16, 17] or
  • Cisplatin 60 mg/m2 IV on day 1 plus irinotecan 60 mg/m2 IV on days 1, 8, and 15 every 28d[9, 12, 13] or
  • Cisplatin 30 mg/m2 IV on days 1 and 8 or 80 mg/m2 IV on day 1 plus  irinotecan 65 mg/m2 IV on days 1 and 8 every 21d[8, 10] or
  • Carboplatin AUC 5 IV on day 1 plus  irinotecan 50 mg/m2 IV on days 1, 8, and 15 every 28d[15, 17] or
  • Carboplatin AUC 4-5 IV on day 1 plus  irinotecan 150-200 mg/m2 IV on day 1 every 21d[18, 19, 20] or
  • Cyclophosphamide 800-1000 mg/m2 IV on day 1 plus doxorubicin 40-50 mg/m2 IV on day 1 plus vincristine 1-1.4 mg/m2 IV on day 1 every 21-28d[21, 22, 23]

Second-line chemotherapy for relapsed or refractory disease

Stage IV disease[8] :

  • Second-line chemotherapy is given for at least 4-6 cycles but can be given until disease progression as tolerated in some cases
  • Patients who have relapsed disease more than 6mo after completing first-line chemotherapy can be treated with that original first-line regimen (typically a platinum-based doublet) again, with and expected response rate of 62-100%[2, 1]
  • Etoposide 50 mg/m2 PO daily for 3wk every 4wk[24] or
  • Topotecan 2.3 mg/m2 PO on days 1-5 every 21d[25, 26, 27] or
  • Topotecan 1.5 mg/m2 IV on days 1-5 every 21d[25, 26, 28] or
  • Carboplatin AUC 5 IV on day 1 plus  irinotecan 50 mg/m2 IV on days 1, 8, and 15 every 28d[15, 17] or
  • Carboplatin AUC 4 - 5 IV on day 1 plus  irinotecan 150-200 mg/m2 IV on day 1 every 21d[18, 19, 20] or
  • Cisplatin 30 mg/m2 IV on days 1, 8, and 15 plus  irinotecan 60 mg/m2 IV on days 1, 8, and 15 every 28d[29] or
  • Cisplatin 60 mg/m2 IV on day 1 plus  irinotecan 60 mg/m2 IV on days 1, 8, and 15 every 28d[9, 13] or
  • Cisplatin 30 mg/m2 IV on days 1 and 8 or 80 mg/m2 IV on day 1 plus  irinotecan 65 mg/m2 IV on days 1 and 8 every 21d[8, 10] or
  • Paclitaxel 80 mg/m2 IV weekly for 6wk every 8wk[30] or
  • Paclitaxel 175 mg/m2 IV on day 1 every 3wk[31]
  • Institution Review Board (IRB) - approved clinical trial

Third-line chemotherapy for relapsed or refractory disease

Stage IV disease[1] :

  • Etoposide 50 mg/m2 PO daily for 3wk every 4wk[24] or
  • Topotecan 2.3 mg/m2 PO on days 1-5 every 21d[25, 26, 27] or
  • Topotecan 1.5 mg/m2 IV on days 1-5 every 21d[25, 26, 28] or
  • Carboplatin AUC 5 IV on day 1 plus irinotecan 50 mg/m2 IV on days 1, 8, and 15 every 28d[15, 17] or
  • Carboplatin AUC 4-5 IV on day 1 plus irinotecan 150-200 mg/m2 IV on day 1 every 21d[18, 19, 20] or
  • Cisplatin 30 mg/m2 IV on days 1, 8, and 15 plus irinotecan 60 mg/m2 IV on days 1, 8, and 15 every 28d[29] or
  • Cisplatin 60 mg/m2 IV on day 1 plus irinotecan 60 mg/m2 IV on days 1, 8, and 15 every 28d[9, 13] or
  • Cisplatin 30 mg/m2 IV on days 1 and 8 or 80 mg/m2 IV on day 1 plus irinotecan 65 mg/m2 IV on days 1 and 8 every 21d[8, 10] or
  • Paclitaxel 80 mg/m2 IV weekly for 6wk every 8wk[30] or
  • Paclitaxel 175 mg/m2 IV on day 1 every 3wk[30]
  • IRB-approved clinical trial

Special considerations

See the list below:

  • Patients with mixed SCLC/non-SCLC histology should be given the same treatment as patients with SCLC[1, 2]
  • Prophylactic cranial irradiation is recommended for SCLC patients with a complete or partial remission (total of 25 Gy in 10 fractions or 30 Gy in 10-15 fractions)[1, 2]
  • Dose dense or dose escalation chemotherapy regimens are not recommended outside of a randomized clinical trial[1, 2]
  • Patients with brain metastases can receive chemotherapy prior to brain radiation due to high response rates with chemotherapy[1, 2]
  • An advancement in treatment has come with the emergence of immune checkpoint inhibitors. Studies are now investigating the administration of single-agent pembrolizumab in patients with non-SCLC[32]
  • A study evaluating treatment of patients with stereotactic body radiation therapy concluded that it is a promising alternative to surgery for patients with stage I non-SCLC[33]
 
Contributor Information and Disclosures
Author

Marvaretta M Stevenson, MD Assistant Professor, Division of Medical Oncology, Duke University Medical Center, Durham, NC

Disclosure: Nothing to disclose.

Specialty Editor Board

Jasmeet Anand, PharmD, RPh Adjunct Instructor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Christopher D Braden, DO Hematologist/Oncologist, Chancellor Center for Oncology at Deaconess Hospital

Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD, FACP, FRCPC Clinical Professor of Medicine, Section of Hematology/Oncology, University of Arizona College of Medicine, Arizona Cancer Center

Jules E Harris, MD, FACP, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Society of Hematology, Central Society for Clinical and Translational Research, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

References
  1. NCCN Clinical Practice Guidelines in Oncology: Small Cell Lung Cancer. V. 2.2013. Available at http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. Accessed: May 12, 2013.

  2. Pazdur R, Wagman L, Camphausen K, Hoskins W, eds. Cancer Management: A Multidisciplinary Approach. 12th ed. Norwalk, Connecticut: CMP Healthcare Media LLC; 2009.

  3. Turrisi AT 3rd, Kim K, Blum R, et al. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. 1999. 340:265-71.

  4. Takada M, Fukuoka M, Kawahara M, et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol. 2002. 20:3054-60.

  5. Skarlos DV, Samantas E, Briassoulis E, et al. Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG). Ann Oncol. 2001 Sep. 12(9):1231-8. [Medline].

  6. Smith IE, Evans BD, Gore ME, et al. Carboplatin (Paraplatin; JM8) and etoposide (VP-16) as first-line combination therapy for small-cell lung cancer. J Clin Oncol. 1987. 5:185-9.

  7. Eckardt JR, von Pawel J, Papai Z, et al. Open-label, multicenter, randomized, phase III study comparing oral topotecan/cisplatin versus etoposide/cisplatin as treatment for chemotherapy-naive patients with extensive-disease small-cell lung cancer. J Clin Oncol. 2006. 24:2044-51.

  8. Zatloukal P, Cardenal F, Szczesna A, et al. A multicenter international randomized phase III study comparing cisplatin in combination with irinotecan or etoposide in previously untreated small-cell lung cancer patients with extensive disease. Ann Oncol. 2010. 21:1810-6.

  9. Lara PN, Jr., Natale R, Crowley J, et al. Phase III trial of irinotecan/cisplatin compared with etoposide/cisplatin in extensive-stage small-cell lung cancer: clinical and pharmacogenomic results from SWOG S0124. J Clin Oncol. 2009. 27:2530-5.

  10. Hanna N, Bunn PA Jr, Langer C, et al. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol. 2006. 24:2038-43.

  11. Ihde DC, Mulshine JL, Kramer BS, et al. Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer. J Clin Oncol. 1994. 12:2022-34.

  12. Natale RB, Lara PN, Chansky K, et al. S0124: A randomized phase III trial comparing irinotecan/cisplatin (IP) with etoposide/cisplatin (EP) in patients (pts) with previously untreated extensive stage small cell lung cancer (E-SCLC). 2008 ASCO Annual Meeting, abstract 7512.

  13. Noda K, Nishiwaki Y, Kawahara M, et al. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med. 2002. 346:85-91.

  14. Okamoto H, Watanabe K, Kunikane H, et al. Randomised phase III trial of carboplatin plus etoposide vs split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer: JCOG 9702. Br J Cancer. 2007. 97:162-9.

  15. Schmittel AH, Sebastian M, Weikersthal LFv, et al. Irinotecan plus carboplatin versus etoposide plus carboplatin in extensive disease small cell lung cancer: Results of the German randomized phase III trial. 2009 ASCO Annual Meeting, abstract 8029.

  16. Quoix E, Breton JL, Daniel C, et al. Etoposide phosphate with carboplatin in the treatment of elderly patients with small-cell lung cancer: a phase II study. Ann Oncol. 2001. 12:957-62.

  17. Schmittel A, Fischer von Weikersthal L, Sebastian M, et al. A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients with extended disease small-cell lung cancer. Ann Oncol. 2006. 17:663-7.

  18. Hermes A, Bergman B, Bremnes R, et al. Irinotecan plus carboplatin versus oral etoposide plus carboplatin in extensive small-cell lung cancer: a randomized phase III trial. J Clin Oncol. 2008. 26:4261-7.

  19. Hermes A, Bergman B, Bremnes R, et al. A randomized phase III trial of irinotecan plus carboplatin versus etoposide plus carboplatin in patients with small cell lung cancer, extensive disease (SCLC-ED): IRIS-study. 2007 ASCO Annual Meeting, abstract 7523.

  20. Chen G, Huynh M, Fehrenbacher L, et al. Phase II trial of irinotecan and carboplatin for extensive or relapsed small-cell lung cancer. J Clin Oncol. 2009. 27:1401-4.

  21. Fukuoka M, Furuse K, Saijo N, et al. Randomized trial of cyclophosphamide, doxorubicin, and vincristine versus cisplatin and etoposide versus alternation of these regimens in small-cell lung cancer. J Natl Cancer Inst. 1991. 83:855-61.

  22. 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. 10:282-91.

  23. 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. 17:658-67.

  24. Johnson DH, Greco FA, Strupp J, Hande KR, Hainsworth JD. Prolonged administration of oral etoposide in patients with relapsed or refractory small-cell lung cancer: a phase II trial. J Clin Oncol. 1990. 8:1613-7.

  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. 25:2086-92.

  26. von Pawel J, Gatzemeier U, Pujol JL, et al. Phase ii comparator study of oral versus intravenous topotecan in patients with chemosensitive small-cell lung cancer. J Clin Oncol. 2001. 19:1743-9.

  27. O'Brien ME, 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. 24:5441-7.

  28. Ardizzoni A, Hansen H, Dombernowsky P, et al. Topotecan, a new active drug in the second-line treatment of small-cell lung cancer: a phase II study in patients with refractory and sensitive disease. The European Organization for Research and Treatment of Cancer Early Clinical Studies Group and New Drug Development Office, and the Lung Cancer Cooperative Group. J Clin Oncol. 1997. 15:2090-6.

  29. Ando M, Kobayashi K, Yoshioka H, et al. Weekly Administration of Irinotecan (CPT-11) Plus Cisplatin (CDDP) for Refractory or Relapsed Small Cell Lung Cancer (SCLC). ASCO Annual Meeting, abstract 1273.

  30. Yamamoto N, Tsurutani J, Yoshimura N, et al. Phase II study of weekly paclitaxel for relapsed and refractory small cell lung cancer. Anticancer Res. 2006. 26:777-81.

  31. Smit EF, Fokkema E, Biesma B, Groen HJ, Snoek W, Postmus PE. A phase II study of paclitaxel in heavily pretreated patients with small-cell lung cancer. Br J Cancer. 1998. 77:347-51.

  32. Dang TO, Ogunniyi A, Barbee MS, Drilon A. Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Expert Rev Anticancer Ther. 2015 Nov 20. [Medline].

  33. Nagata Y, Hiraoka M, Shibata T, Onishi H, Kokubo M, Karasawa K, et al. Prospective Trial of Stereotactic Body Radiation Therapy for Both Operable and Inoperable T1N0M0 Non-Small Cell Lung Cancer: Japan Clinical Oncology Group Study JCOG0403. Int J Radiat Oncol Biol Phys. 2015 Dec 1. 93 (5):989-96. [Medline].

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