Lung Cancer Treatment Regimens

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LUNG CANCER TREATMENT REGIMENS

The selection, dosing, and administration of anticancer agents and the management of associated toxicities are complex. Drug dose modifications and schedule and initiation of supportive care interventions are often necessary because of expected toxicities and because of individual patient variability, prior treatment, and comorbidities. Thus, the optimal delivery of anticancer agents requires a healthcare delivery team experienced in the use of such agents and the management of associated toxicities in patients with cancer. The cancer treatment regimens below may include both FDA-approved and unapproved uses/regimens and are provided as references only to the latest treatment strategies. Clinicians must choose and verify treatment options based on the individual patient.

NOTE: Grey shaded boxes contain updated regimens.

General treatment notes for NSCLC:

  • Regarding concurrent chemotherapy and radiotherapy, data support full-dose cisplatin over carboplatin-based regimens; carboplatin regimens have not been adequately tested.1
  • Principles for treating advanced disease:1
    • Platinum-based chemotherapy prolongs survival, improves symptom control, and yields superior quality of life compared with best supportive care.
    • No specific platinum-based cytotoxic combination is clearly superior to another.
    • Patients with performance statuses of 3 or 4, of any age, do not benefit from cytotoxic treatment, except erlotinib for epidermal growth factor receptor (EGFR) mutation–positive patients.
    • Histology is important in treatment selection.

REGIMEN

DOSING

Non-Small Cell Lung Cancer (NSCLC)

Chemotherapy for Adjuvant Therapy

Cisplatin (Platinol; CDDP) + vinorelbine (Navelbine)1–4

Days 1 and 8: Cisplatin 50mg/m2 IV, plus

Days 1, 8, 15 and 22: Vinorelbine 25mg/m2 IV.

Repeat cycle every 4 weeks for 4 cycles.

or

Day 1: Cisplatin 100mg/m2 IV, plus

Days 1, 8, 15 and 22: Vinorelbine 30mg/m2 IV.

Repeat cycle every 4 weeks for 4 cycles.

Cisplatin + etoposide (Toposar, VePesid, Etopophos; VP-16)1, 3

Day 1: Cisplatin 100mg/m2 IV, plus

Days 1–3: Etoposide 100mg/m2 IV.

Repeat cycle every 4 weeks for 4 cycles.

Cisplatin + vinblastine (Velban)1,3

Days 1: Cisplatin 80mg/m2 IV.

Repeat cycle every 3 weeks for 4 cycles.

Days 1, 8, 15 and 22: Vinblastine 4mg/m2 IV, then every 2 weeks after Day 43 until last cisplatin administration.

Cisplatin + gemcitabine (Gemzar)1

Day 1: Cisplatin 75mg/m2 IV, plus

Days 1 and 8: Gemcitabine 1,250mg/m2 IV.

Repeat cycle every 3 weeks.

Cisplatin + docetaxel (Taxotere)1,5

Day 1: Docetaxel 75mg/m2 IV + cisplatin 75mg/m2 IV.

Repeat cycle every 3 weeks.

Cisplatin + pemetrexed (Alimta)1

Day 1: Cisplatin 75mg/m2 IV + pemetrexed 500mg/m2 IV.

Repeat cycle every 3 weeks for 4 cycles.

(For adenocarcinoma and large cell carcinoma and NSCLC NOS without specific histologic subtype)

Paclitaxel (Taxol) + carboplatin (Paraplatin)1,6

Day 1: Paclitaxel 200mg/m2 IV + carboplatin AUC=6mg/mL/min IV.

Repeat cycle every 3 weeks for 4 cycles.

Concurrent Chemotherapy and Radiotherapy (RT)

Cisplatin + etoposide1,7

Days 1, 8, 29 and 36: Cisplatin 50mg/m2 IV, plus

Days 1–5 and 29–33: Etoposide 50mg/m2 IV, plus

Concurrent thoracic RT 1.8Gy/day for 5 days/week (total dose, 61Gy); preferred regimen.

Cisplatin + vinblastine1,8

Days 1 and 29: Cisplatin 100mg/m2 IV, plus

Days 1, 8, 15, 22 and 29: Vinblastine 5mg/m2 IV.

Concurrent thoracic RT (total dose, 60Gy); preferred regimen.

Sequential Chemotherapy and Radiotherapy (RT)

Cisplatin + vinblastine1,8

Days 1 and 29: Cisplatin 100mg/m2 IV.

Days 1, 8, 15, 22 and 29: Vinblastine 5mg/m2 IV followed by

RT with 60Gy in 30 fractions beginning on Day 50.

Paclitaxel + carboplatin1,9

Day 1: Paclitaxel 200mg/m2 IV + carboplatin AUC=6mg/mL/min IV.

Repeat cycle every 3 weeks; 2 cycles, followed by

thoracic RT 63Gy beginning on Day 42.

Systemic Therapy for Advanced Disease—First-Line

Bevacizumab (Avastin) + carboplatin and paclitaxel1,10,11

Day 1: Paclitaxel 200mg/m2 IV.

Day 1: Carboplatin AUC 6 IV.

Repeat every 3 weeks for 6 cycles.

Day 1: Bevacizumab 15mg/kg IV every 3 weeks until disease progression.

Cetuximab (Erbitux) + cisplatin and vinorelbine1,12

Day 1: Cetuximab 400mg/m2 IV + cisplatin 80mg/m2 IV, plus

Days 1 and 8: Vinorelbine 25mg/m2 IV, plus

Day 8: Cetuximab 250mg/m2 IV once weekly.

Repeat cycle every 3 weeks for 6 cycles.

Indicated in advanced NSCLC

Erlotinib (Tarceva)1,13,14

Day 1: Erlotinib 150mg orally once daily; following 4 cycles of platinum-based chemotherapy.

Indicated for EGFR mutation-positive patients and may be considered as an option for patients who test positive for an EGFR mutation.

Cisplatin + paclitaxel1,15

Day 1: Paclitaxel 135mg/m2 IV over 24 hrs.

Day 2: Cisplatin 75mg/m2 IV.

Repeat every 3 weeks.

Cisplatin + gemcitabine1,15

Day 1: Cisplatin 100mg/m2 IV.

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

Repeat every 4 weeks.

Cisplatin + docetaxel1,5

Day 1: Cisplatin 75mg/m2 IV.

Day 1: Docetaxel 75mg/m2 IV.

Repeat every 3 weeks.

Cisplatin + vinorelbine1,5

Day 1: Cisplatin 100mg/m2 IV.

Days 1, 8, 15 and 22: Vinorelbine 25mg/m2 IV over 10 min.

Repeat every 4 weeks.

Carboplatin + paclitaxel1,15

Day 1: Carboplatin AUC 5-6 IV.

Day 1: Paclitaxel 225mg/m2 IV over 3 hours.

Repeat every 3 weeks.

Pemetrexed (Alimta) + cisplatin1,16,17

Day 1: Pemetrexed 500mg/m2 IV + cisplatin 75mg/m2 IV.

Repeat cycle every 3 weeks.

Crizotinib (Xalkori)1,18

Crizotinib 250mg orally twice daily.

May reduce to 200mg twice daily not tolerated or toxicity occurs. If further reduction is needed, reduce to 250mg once daily.

Indicated for ALK-positive patients.

Systemic Therapy for Advanced Disease—Second-Line

Docetaxel or

Pemetrexed or

Erlotinib1,19–21

*In patients who have experienced disease progression either during or after first-line therapy, single-agent docetaxel, pemetrexed, or erlotinib are established second-line agents.

Day 1: Docetaxel 75mg/m2 IV.

Repeat cycle every 3 weeks.

Docetaxel has proved superior to BSC, vinorelbine, or ifosfamide with improved survival and quality of life.

or

Day 1: Pemetrexed 500mg/m2 IV.

Repeat cycle every 3 weeks.

Pemetrexed has been shown to be superior to docetaxel with less toxicity in patients with adenocarcinoma and large cell carcinoma (non-squamous histology).

or

Day 1: Erlotinib 150mg orally once daily.

Erlotinib has proved superior to BSC with significantly improved survival and delayed time to symptom deterioration in NSCLC patients previously treated with chemotherapy.

Systemic Therapy for Advanced Disease—Third-Line

Erlotinib1,21

Day 1: Erlotinib 150mg orally once daily.

Erlotinib has proved superior to BSC with significantly improved survival and delayed time to symptom deterioration in patients who previously failed first- and second-line chemotherapy.

General treatment note for SCLC:

  • During chemotherapy plus radiation therapy, cisplatin/etoposide therapy is preferred.1
  • Clinical trial preferred in second-line/relapsed disease setting.1

Small Cell Lung Cancer (SCLC)

Limited Stage

Cisplatin + etoposide1,22,23

NOTE: Category 1

Day 1: Cisplatin 60mg/m2 IV, plus

Days 1–3: Etoposide 120mg/m2 IV.

Repeat cycle every 3 weeks for at least 4 cycles.

Radiotherapy 1.8Gy once daily to 54–61Gy or 1.5Gy twice daily to 45Gy.

Cisplatin + etoposide1,24

NOTE: Category 1

Day 1: Cisplatin 80mg/m2 IV, plus

Days 1–3: Etoposide 100mg/m2 IV.

Repeat every 4 weeks for 4–6 cycles.

Carboplatin + etoposide1,25

Day 1: Carboplatin AUC 5–6 IV, plus

Days 1–3: Etoposide 100mg/m2 IV.

Repeat cycle every 3 weeks for 4–6 cycles.

Extensive Stage

Cisplatin + etoposide1,26

Day 1: Cisplatin 80mg/m2 IV.

Days 1–3: Etoposide 80mg/m2 IV.

Repeat every 3 weeks for 4–6 cycles.

Cisplatin + etoposide1,27

Days 1: Cisplatin 75mg/m2 IV.

Days 1–3: Etoposide 100mg/m2 IV.

Repeat every 3 weeks for 4–6 cycles.

Cisplatin + etoposide1,28

Days 1–3: Cisplatin 25mg/m2 IV + etoposide 100mg/m2.

For 4–6 cycles.

Cisplatin + irinotecan1,22,29,30

Day 1: Cisplatin 60mg/m2 IV.

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

Repeat cycle every 4 weeks for 4 cycles.

OR

Day 1 and 8: Cisplatin 30mg/m2 IV.

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

Repeat every 3 weeks for 4–6 cycles.

Carboplatin + irinotecan1,31

Day 1: Carboplatin AUC=5mg/mL/min IV, plus

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

Repeat cycle every 4 weeks for 4–6 cycles.

Carboplatin + Etoposide1,32

Day 1: Carboplatin AUC 5–6.

Days 1–3: Etoposide 100mg/m2 IV.

Repeat every 4 weeks for 4–6 cycles.

Second-Line/Relapse Disease

Topotecan (for relapse >2–3 months up to 6 months)1,33–35

NOTE: Category 1

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

Repeat every 3 weeks.

OR

Days 1–5: Topotecan 1.5mg/m2 day IV over 30 min.

Repeat every 3 weeks.

References

  1. NCCN Clinical Practice Guidelines in Oncology™.

      Non-Small Cell Lung Cancer. v 3.2012. Available at http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed April 20, 2012.

      Small Cell Lung Cancer. v 2.2012. Available at http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. Accessed April 20, 2012.

  2. Winton T, Livingston R, Johnson D, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-lung cancer. N Engl J Med. 2005;352:2589–2597.

  3. Arriagada R, Bergman B, Dunant A, et al. The International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small cell lung cancer. N Engl J Med. 2004;350:351–360.

  4. Douillard JY, Rosell R, De Lena M, et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol. 2006;7:719–727.

  5. Fossella F, Pereira JR, von Pawel J, et al. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003;21:3016–3024.

  6. Strauss GM, Herndon JE III, Maddaus MA, et al. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study groups. J Clin Oncol. 2008;26:5043–5051.

  7. Albain KS, Crowley JJ, Turrisi AT III, et al. Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB non-small-cell lung cancer: a Southwest Oncology Group phase II study, SWOG 9019. J Clin Oncol. 2002;20:3454–3460.

  8. Curran WJ, Scott CB, Langer CJ, et al. Long-term benefit is observed in a phase III comparison of sequential vs concurrent chemo-radiation for patients with unresectable stage III NSCLC: RTOG 94-10. Proc Am Soc Clin Oncol. 22:621a, 2003 (abstr 2499).

9. Gandara DR, Chansky K, Albain KS, et al. Consolidation docetaxel after concurrent chemoradiotherapy in stage IIIB non-small-cell lung cancer: phase II Southwest Oncology Group study S9504. J Clin Oncol. 2003;21:2004–2010.

10. Avastin [prescribing information]. South San Francisco, CA: Genentech, Inc.; 2011.

11. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Eng J Med. 2006;355:2542–2550.

12. Pirker R, Pereira JR, Szczesna A, et al. FLEX Study Team. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009;373:1525–1531.

13. Cappuzzo F, Ciuleanu T, Stelmakh L, et al. SATURN investigators. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2010;11:521–529.

14. Tarceva [prescribing information]. S. San Francisco, CA: Genentech, Inc.; 2011.

15. Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Eng J Med. 2002;346:92–98.

16. Alimta® [prescribing information]. Indianapolis, IN: Eli Lilly & Co.; 2011.

17. Scagliotti GV, Parikh P, von Pawel J, et al. 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. 2008;26:3543–3551.

18. Xalkori [prescribing information]. New York, NY: Pfizer, Inc.; 2011.

19. Fossella FV, DeVore R, Kerr RN, et al. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non–small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. J Clin Oncol. 2000;18:2354–2362.

20. Hanna N, Shepherd FA, Fossella FV, et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004;22:1589–1597.

21. Shepherd FA, Rodrigues Pereira J, Ciuleanu T et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005;353:123–132.

22. 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.

23. 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 Eng J Med. 1999;340:265–271.

24. Saito H, Takada Y, Ichinose Y, et al. West Japan Thoracic Oncology Group 9902. Phase II study of etoposide and cisplatin with concurrent twice-daily thoracic radiotherapy followed by irinotecan and cisplatin in patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology Group 9902. J Clin Oncol. 2006;24:5247–5252.

25. 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.

26. 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;12:2022–2034.

27. Sundstrom S, Bremnes RM, Kaasa S, et al. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002;20:4665–4672.

28. 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.

29. Natale RB 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) [Abstract 7512]. 2008 ASCO annual meeting.

30. 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.

31. Schmittel A, Sebastian M, Fischer von Weikersthal L, et al. For the Arbeitsgemeinschaft Internistische Onkologie thoracic oncology study group. A German multicenter, randomized phase III trial comparing irinotecan-carboplatin with etoposide-carboplatin as first-line therapy for extensive-disease small-cell lung cancer. Ann Oncol. 2011 Jan 25. [Epub ahead of print].

32. 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.

33. 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.

34. O'Brien M, 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.

35. Ardizzoni A, 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; 15:2090–2096.


Lung Cancer Drug Monographs

Respiratory And Thoracic Cancers

Adriamycin Adriamycin Solution Alimta
Avastin Etopophos Gemzar
Hycamtin Hycamtin Capsules Iressa
Methotrexate for Injection Methotrexate Injection Mustargen
Navelbine Photofrin Tarceva
Taxol Taxotere Toposar
Trexall Vepesid Xalkori

Data provided by the Monthly Prescribing Reference (MPR) Hematology/Oncology Edition.
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