Small Cell Lung Cancer Treatment Regimens

Small Cell Lung Cancer Treatment Regimens

Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment.

Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies.


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These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The National Comprehensive Cancer Network Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Note: All recommendations are category 2A unless otherwise indicated.

▶Systemic Therapy as Primary or Adjuvant Therapy1

REGIMEN

DOSING

Limited Stage (maximum of 4–6 cycles)a-c

Preferred Regimens

Cisplatin + Etoposide3-6

Day 1: Cisplatin 60mg/m2 IV over 60 minutes

Days 1–3: Etoposide 120mg/m2 IV over 60 minutes.

Repeat cycle every 3-4 weeks for 4-6 cycles.

OR

Day 1: Cisplatin 75mg/m2 IV over 60 minutes

Days 1–3: Etoposide 100mg/m2 IV over 60 minutes.

Repeat cycle every 3-4 weeks for 4–6 cycles

Other Recommended Regimens

Carboplatin + Etoposide5-8,d

Day 1: Carboplatin AUC 5–6 IV over 30 minutes

Days 1–3: Etoposide 100mg/m2 IV over 60 minutes.

Repeat cycle every 3-4 weeks for 4–6 cycles.

Cisplatin + Etoposide3-6

Days 1-3: Cisplatin 25mg/m2 IV over 60 minutes

Days 1-3: Etoposide 100mg/m2 IV over 60 minutes.

Repeat cycle every 3-4 weeks for 4-6 cycles.

Extensive Stage SCLC (maximum of 4-6 cycles)1

Preferred Regimens

Carboplatin + Etoposide + Atezolizumab (Category 1)9,10,e,f

Day 1: Carboplatin AUC 5 IV over 30 minutes

Days 1-3: Etoposide 100mg/m2 IV over 60 minutes

Day 1: Atezolizumab 1,200mg IV.

Repeat cycle every 3 weeks for 4 cycles.

Day 1: Atezolizumab 1,200mg IV.

Repeat cycle every 3 weeks.

Carboplatin + Etoposide + Durvalumab (Category 1)11,12,e,f

Day 1: Carboplatin AUC 5-6 IV over 30 minutes

Days 1-3: Etoposide 80-100mg/m2 IV over 60 minutes

Day 1: Durvalumab 1,500mg IV over 60 minutes

Repeat cycle every 3 weeks for 4 cycles, followed by maintenance therapy with:

Day 1: Durvalumab 1,500mg IV over 60 minutes.

Repeat cycle every 4 weeks.

Cisplatin + Etoposide + Durvalumab (Category 1)11,12,e,f

Day 1: Cisplatin 75-80mg/m2 IV over 120 minutes

Days 1-3: Etoposide 80-100mg/m2 IV over 60 minutes

Day 1: Durvalumab 1,500mg IV over 60 minutes

Repeat cycle every 3 weeks for 4 cycles, followed by maintenance therapy with:

Day 1: Durvalumab 1,500mg IV over 60 minutes.

Repeat cycle every 4 weeks.

Other Recommended Regimens

Carboplatin + Etoposide5-8

Day 1: Carboplatin AUC 5–6 IV over 30 minutes

Days 1–3: Etoposide 100mg/m2 IV over 60 minutes.

Repeat cycle every 3-4 weeks for 4–6 cycles.

Cisplatin + Etoposide5,6,13-15

Day 1: Cisplatin 75mg/m2 IV over 60 minutes

Days 1–3: Etoposide 100mg/m2 IV over 60 minutes.

Repeat cycle every 3-4 weeks for 4–6 cycles.

OR

Day 1: Cisplatin 80mg/m2 IV over 60 minutes

Days 1–3: Etoposide 80mg/m2 IV over 60 minutes.

Repeat cycle every 3-4 weeks for 4–6 cycles.

OR

Days 1–3: Cisplatin 25mg/m2 IV over 60 minutes

Days 1–3: Etoposide: 100mg/m2 IV over 60 minutes.

Repeat cycle every 3-4 weeks for 4-6 cycles.

Useful in Certain Circumstances

Carboplatin + Irinotecan5,6,16

Day 1: Carboplatin AUC 5 IV over 30 minutes

Days 1, 8, and 15: Irinotecan 50mg/m2 IV over 90 minutes.

Repeat cycle every 4 weeks for 4–6 cycles.

Cisplatin + Irinotecan5,6,15,16,e

Day 1: Cisplatin 60mg/m2 IV over 60 minutes

Days 1, 8, and 15: Irinotecan 60mg/m2 IV over 90 minutes.

Repeat cycle every 4 weeks for 4 cycles.

OR

Day 1 and 8: Cisplatin 30mg/m2 IV over 60 minutes

Day 1 and 8: Irinotecan 65mg/m2 IV over 90 minutes.

Repeat cycle every 3 weeks for 4–6 cycles.

▶Subsequent Systemic Therapy1,g

Relapse ≤6 months, PS 0-2

Preferred Regimensh

Lurbinectedin19

Day 1: Lurbinectedin 3.2 mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks

Topotecan20-22

Days 1–5: Topotecan 1.5mg/m2 IV daily over 30 minutes.

Repeat cycle every 3 weeks.

OR

Days 1–5: Topotecan 2.3mg/m2 orally once daily.

Repeat cycle every 3 weeks.

Other Recommended Regimens

Bendamustine (Category 2B)23

Days 1 and 2: Bendamustine 120mg/m2 IV over 10 minutes or 60 minutes (based on product selection).

Repeat cycle every 3 weeks for 6 cycles.

Cyclophosphamide + Doxorubicin + Vincristine (CAV)21

Day 1: Cyclophosphamide 1,000mg/m2 IV over 60 minutes

Day 1: Doxorubicin 45mg/m2 IV push

Day 1: Vincristine 2mg IV over 5-10 minutes.

Repeat cycle every 3 weeks.

Docetaxel24

Day 1: Docetaxel 60-100 mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks.

Gemcitabine25-26

Days 1, 8, and 15: Gemcitabine 1,000mg/m2 IV over 30 minutes.

Repeat cycle every 4 weeks.

Irinotecan27

Days 1,8,15,22: Irinotecan 100mg/m2 IV over 90 minutes.

Repeat cycle every 4 weeks.

▶Subsequent Systemic Therapy1,g

Relapse ≤6 months, PS 0-2

Other Recommended Regimens

Nivolumab28-30,e,f

Day 1: Nivolumab 240mg IV over 30 minutes

Repeat cycle every 2 weeks.

OR

Day 1: Nivolumab 480mg IV over 30 minutes

Repeat cycle every 4 weeks.

Nivolumab + Ipilimumab28-31,e,f

Day 1: Nivolumab 1mg/kg IV over 30 minutes

Day 1: Ipilimumab 3mg/kg IV over 90 minutes

Repeat cycle every 3 weeks for 4 cycles, followed by:

Day 1: Nivolumab 240mg IV over 30 minutes.

Repeat cycle every 2 weeks.

OR

Day 1: Nivolumab 1mg/kg IV over 30 minutes

Day 1: Ipilimumab 3mg/kg IV over 90 minutes

Repeat cycle every 3 weeks for 4 cycles. followed by:

Day 1: Nivolumab 480mg IV over 30 minutes.

Repeat cycle every 4 weeks.

Oral Etoposide35,36

Days 1–21: Etoposide 50mg/m2 orally once daily.

Repeat cycle every 4 weeks.

Paclitaxel34,35

Day 1: Paclitaxel 175mg/m2 IV over 3 hours.

Repeat cycle every 3 weeks.

OR

Days 1,8,15,22,29,36: Paclitaxel 80mg/m2 IV over 60 minutes.

Repeat cycle every 8 weeks (6 weeks on followed by 2 weeks off).

Pembrolizumab36-38,e,f

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks.

Temozolomide39,40

Days 1–21: Temozolomide 75mg/m2 orally once daily.

Repeat cycle every 4 weeks.

OR

Days 1-5: Temozolomide 200mg/m2 orally once daily.

Repeat cycle every 4 weeks.

Vinorelbine41,42

Days 1, 8, 15: Vinorelbine 25–30mg/m2 IV over 5-10 minutes.

Repeat cycle every 3 weeks.

Relapse >6 months1

Preferred

Original regimen5,6

Other Recommended Regimen

Lurbinectedin19

Day 1: Lurbinectedin 3.2mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks

a  Planned cycle length should be every 21-28 days during concurrent RT.

b  During systemic therapy + radiotherapy, cisplatin/etoposide is recommended (category 1).

c  The use of myeloid growth factors is not recommended during concurrent systemic therapy plus radiotherapy (category 1 for not using GM-CSF).2

d  Cisplatin contraindicated or not tolerated.

e  Regimen is not recommended for relapsed disease in patients on maintenance atezolizumab at time of relapse. For patients who relapse after >6 months of atezolizumab in maintenance therapy, recommend re-treatment with carboplatin + etoposide alone.

f  Contraindications for treatment of PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease and/or concurrent use of immunosuppressive agents.

g  Subsequent systemic therapy refers to second-line and beyond therapy.

References

  1. Referenced with permission from NCCN Clinical Practice Guidelines in Oncology™ Small Cell Lung Cancer. V4.2020. Available at: http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. Accessed July 21, 2020.

  2. Bunn PA, Crowley J, Kelly K, et al. Chemoradiotherapy with or without granulocyte- macrophage colony-stimulating factor in the treatment of limited-stage small-cell lung cancer: a prospective phase III randomized study of the Southwest Oncology Group. J Clin Oncol. 1995;13:1632–1641.

  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;340:265-271.

  4. Faivre-Finn C, Snee M, Ashcroft L, et al. Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial. Lancet Oncol. 2017;18:1116-1125.

  5. Postmus PE, Berendsen HH, van Zandwijk N, et al. Retreatment with the induction regimen in small cell lung cancer relapsing after an initial response to short term chemotherapy. Eur J Cancer Clin Oncol. 1987;23:1409-1411.

  6. Giaccone G, Ferrati P, Donadio M, et al. Reinduction chemotherapy in small cell lung cancer. Eur J Cancer Clin Oncol. 1987;23:1697-1699.

  7. 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;12:1231-1238.

  8. Okamoto H, Watanabe K, Nishiwaki Y, et al. Phase II study of area under the plasma-concentration-versus-time curve-based carboplatin plus standard-dose intravenous etoposide in elderly patients with small-cell lung cancer. J Clin Oncol. 1999;17:3540-3545.

  9. Atezolizumab (Tecentriq) [package insert]. South San Francisco, CA: Genentech, Inc; 2019.

10. Horn L, Mansfield AS, Szczęsna A, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018;379:2220-2229

11. Durvalumab (Imfinzi) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals, LP: 2020.

12. Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive –stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394:1929-1939.

13. Evans WK, Shepherd FA, Feld R, et al. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol. 1985;3:1471-1477.

14. Spigel DR, Townley PM, Waterhouse DM, et al. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011;29:2215-2222.

15. Niell HB, Herndon JE 2nd, Miller AA, et al. Randomized phase III intergroup trial of etoposide and cisplatin with or without paclitaxel and granulocyte colony-stimulating factor in patients with extensive-stage small-cell lung cancer: Cancer and Leukemia Group B Trial 9732. J Clin Oncol. 2005;23:3752-3759.

16. 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;17:663-667.

17. 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.

18. 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;24:2038-2043.

19. Trigo J, Subbiah V, Besse B, et al. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol. 2020;21:645-654.

20. 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;25:2086-2092.

21. 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;17:658-667.

22. 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;24:5441-5447.

23. Lammers PE, Shyr Y, Li CI, et al. Phase II study of bendamustine in relapsed chemotherapy sensitive or resistant small-cell lung cancer. J Thorac Oncol. 2014;9:559-562.

24. Smyth JF, Smith IE, Sessa C, et al. Activity of docetaxel (Taxotere) in small cell lung cancer. The Early Clinical Trials Group of the EORTC. Eur J Cancer. 1994;30A:1058-1060.

25. van der Lee I, Smit EF, van Putten JW, et al. Single-agent gemcitabine in patients with resistant small-cell lung cancer. Ann Oncol. 2001;12:557-561.

26. Masters GA, Declerck L, Blanke C, et al. Phase II trial of gemcitabine in refractory or relapsed small-cell lung cancer: Eastern Cooperative Oncology Group Trial 1597. J Clin Oncol. 2003;21:1550-1555.

27. 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;10:1225-1229.

28. Nivolumab (Opdivo) [package insert]. [package insert]. Princeton, NJ: Bristol-Myers Squibb Co.: 2019.

29. Antonia SJ, López-Martin JA, Bendell J, et al. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol. 2016;17:883-895.

30. Zhao X, Ivaturi V, Gopalakrishnan M, et al. A model-based exposure-response (E-R) assessment of a nivolumab (NIVO) 4-weekly (Q4W) dosing schedule across multiple tumor types. Cancer Res. 2017;77(13 Supplement):Abstract CT101.

31. Ipilimumab (Yervoy) [package insert]. Princeton, NJ: Bristol-Myers Squibb Co.: 2019.

32. Einhorn LH, Pennington K, McClean J. Phase II trial of daily oral VP-16 in refractory small cell lung cancer. Semin Oncol. 1990;17:32–35.

33. Johnson DH, Greco FA, Strupp J, et al. Prolonged administration of oral etoposide in patients with relapsed or refractory small-cell lung cancer: a phase II trial. J Clin Oncol. 1990;8:1613–1617.

34. 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;26:777-781.

35. Smit EF, Fokkema E, Biesma B, et al. A phase II study of paclitaxel in heavily pretreated patients with small-cell lung cancer. Br J Cancer. 1998;77:347-351.

36. Pembrolizumab (Keytruda) [package insert] Whitehouse Station, NJ: Merck & Co., Inc.; 2019.

37. Chung HC, Lopez-Martin JA, Kao SC-H, et al. Phase 2 study of pembrolizumab in advanced small cell lung cancer (SCLC): KEYNOTE-158. J Clin Oncol. 2018;36(15-suppl):Abstract 8506.

38. Ott PA, Elez E, Hiret S, Kim DW, et al. Pembrolizumab in Patients With Extensive-Stage Small-Cell Lung Cancer: Results From the Phase Ib KEYNOTE-028 Study. J Clin Oncol. 2017;35:3823-3829.

39. Pietanza MC, Kadota K, Huberman K, et al. Phase II trial of temozolomide in patients with relapsed sensitive or refractory small cell lung cancer, with assessment of methylguanine-DNA methyltransferase as a potential biomarker. Clin Cancer Res. 2012;18:1138-1145.

40. Zauderer MG, Drilon A, Kadota K, et al. Trial of a 5-day dosing regimen of temozolomide in patients with relapsed small cell lung cancers with assessment of methylguanine-DNA methyltransferase. Lung Cancer. 2014;86:237-240.

41. Jassem J, Karnicka-Młodkowska H, van Pottelsberghe C, et al. Phase II study of vinorelbine (Navelbine) in previously treated small cell lung cancer patients. EORTC Lung Cancer Cooperative Group. Eur J Cancer. 1993;29A:1720-1722.

42. Furuse K, Kubota K, Kawahara M, et al. Phase II study of vinorelbine in heavily previously treated small cell lung cancer. Japan Lung Cancer Vinorelbine Study Group. Oncology. 1996;53:169-172.

(Revised 8/2020; NCCN Small-Cell Lung Cancer Guidelines v4.2020) © 2020 Haymarket Media, Inc.