Small cell carcinoma of the lung medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Patients with small cell carcinoma (SCC) of the lung have many treatment options. The selection depends on the stage of the tumor. The options are radiation therapy, chemotherapy, surgery, or a combination of these methods. Before treatment starts, ask your health care team about possible side effects and how treatment may change your normal activities. Because cancer treatments often damage healthy cells and tissues, side effects are common. Side effects may not be the same for each person, and they may change from one treatment session to the next.

Initial Medical Therapy

Limited Stage SCC

 
 
 
 
 
 
 
 
 
 
 
 
Limited stage SCC
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical stage T(1-2),N(0)
 
 
 
 
 
 
 
 
 
Limited stage in excess of T(1-2),N(0)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
What is the statuses of the pathologic mediastinal staging AND operability of the patient?
 
 
 
 
 
 
 
 
 
What is the performance status of the patient?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Negative pathologic mediastinal staging
AND
Patient is medically operable
 
 
 
 
 
Positive pathologic mediastinal staging
OR
Patient is medically operable
 
Good (PS 0-2)
 
Poor (PS 3-4) due to SCC
 
Poor (PS 3-4) not due to SCC
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Lobectomy
PLUS
Lymph node dissection or sampling
 
 
 
 
 
What is the performance status of the patient?
 
Chemotherapy
PLUS
Thoracic radiation therapy
 
Chemotherapy
WITH/WITHOUT
Thoracic radiation therapy
 
Individualized treatment
PLUS
supportive care
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
What is the status of involvement of the lymph nodes?
 
 
 
Good (PS 0-2)
 
Poor (PS 3-4) due to SCC
 
Poor (PS 3-4) not due to SCC
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
N0
 
N+
 
Chemotherapy
PLUS
Thoracic radiation therapy
 
Chemotherapy
WITH/WITHOUT
Thoracic radiation therapy
 
Individualized treatment
PLUS
supportive care
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chemotherapy
 
Chemotherapy
PLUS
Mediastinal radiotherapy
 
 

Extensive Stage

 
 
 
 
 
 
 
 
 
 
Extensive stage
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Is there symptomatic localized metastasis
OR
brain metastasis?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
 
 
 
 
Yes, there is symptomatic localized metastasis
 
 
 
 
 
Yes, there is brain metastasis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
What is the performance status of the patient?
 
 
 
 
 
What metastasis related symptoms does the patient have?
 
 
 
 
 
Is the patient symptomatic?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Good (PS 0-2)
OR
Poor (3-4) due to SCLC
 
Poor (3-4) not due to SCLC
 
Superior vena cava syndrome
OR
Lobar obstruction
OR
Bone metastasis
 
Spinal cord compression
 
Yes
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Combination chemotherapy
PLUS
Supportive care
 
Individualized therapy
PLUS
Supportive care
 
Chemotherapy
WITH/WITHOUT
Radiation therapy to the sites of metastasis
 
Radiation therapy to the sites of metastasis
THEN
Chemotherapy (unless medical therapy is immediately necessary)
 
Whole brain radiation therapy
THEN
Chemotherapy (unless medical therapy is immediately necessary)
 
Chemotherapy
THEN
Whole brain radiation therapy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Is the patient at elevated risk for fracture?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Palliative external beam radiation therapy
PLUS
Orthopedic stabilization
 
No additional measures
 
 
 
 
 
 
 
 
 

Adjuvant Medical Therapy

Choices for Initial or Adjuvant Chemotherapy

Shown below is a table depicting the different choices of regimens for the initial or adjuvant chemotherapy of patients with small cell carcinoma of the lung. The list of regimens has been adapted from the National Comprehensive Cancer Network (NCCN) guidelines.[1]

Choices for initial or adjuvant chemotherapy (maximum number of cycles: 4-6)
Limited stage SCLC
Cisplatin 60 mg/m2 (day 1)
PLUS
Etoposide 120 mg/m2 (day 1, 2, 3)[2]
Cisplatin 80 mg/m2 (day 1)
PLUS
Etoposide 100 mg/m2 (day 1, 2, 3)[3]
Carboplatin AUC 5-6 (day 1)
PLUS
Etoposide 100 mg/m2 (day 1, 2, 3)[4]
Extensive stage SCLC
Cisplatin 75 mg/m2 (day 1)
PLUS
Etoposide 100 mg/m2 (day 1, 2, 3)[5]
Cisplatin 80 mg/m2 (day 1)
PLUS
Etoposide 80 mg/m2 (day 1, 2, 3)[6]
Cisplatin 25 mg/m2 (day 1, 2, 3)
PLUS
Etoposide 100 mg/m2 (day 1, 2, 3)[7]
Carboplatin AUC 5-6 (day 1)
PLUS
Etoposide 100 mg/m2 (day 1, 2, 3)[8]
Cisplatin 60 mg/m2 (day 1)
PLUS
Irinotecan 60 mg/m2 (day 1, 8, 15)[9]
Cisplatin 30 mg/m2 (day 1)
PLUS
Irinotecan 65 mg/m2 (day 1, 8, 21)[10]
Carboplatin AUC 5 (day 1)
PLUS
Irinotecan 50 mg/m2 (day 1, 8, 15)[11]

Therapy for Relapse or Progressive Disease

 
 
Therapy for relapse of progressive disease
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
What is the performance status of the patient?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Good (PS 0-2)
 
Poor (PS 3-4)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chemotherapy
OR
Palliative therapy
 
Palliative therapy
 
 

Choices for Chemotherapy for Relapse or Progressive Disease

  • Among patients receiving chemotherapy for relapse, the involvement in clinical trials is encouraged.[1]
  • The suggested choices for chemotherapy depend on the duration of time that elapsed between the completion of the initial regimen and the relapse.
    • If the relapse occurred more than 6 months following the initial treatment, the initial chemotherapy regimen should be repeated.[1]

References

  1. 1.0 1.1 1.2 1.3 1.4 NCCN Clinical Practice Guidelines in Oncology. Small Cell Lung Cancer, version 2.2014
  2. Turrisi AT, Kim K, Blum R, Sause WT, Livingston RB, Komaki R; et al. (1999). "Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide". N Engl J Med. 340 (4): 265–71. doi:10.1056/NEJM199901283400403. PMID 9920950.
  3. Saito H, Takada Y, Ichinose Y, Eguchi K, Kudoh S, Matsui K; et al. (2006). "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. 24 (33): 5247–52. doi:10.1200/JCO.2006.07.1605. PMID 17114657.
  4. Skarlos DV, Samantas E, Briassoulis E, Panoussaki E, Pavlidis N, Kalofonos HP; et al. (2001). "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. 12 (9): 1231–8. PMID 11697833.
  5. Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R; et al. (2002). "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. 20 (24): 4665–72. PMID 12488411.
  6. Ihde DC, Mulshine JL, Kramer BS, Steinberg SM, Linnoila RI, Gazdar AF; et al. (1994). "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. 12 (10): 2022–34. PMID 7931470.
  7. Evans WK, Shepherd FA, Feld R, Osoba D, Dang P, Deboer G (1985). "VP-16 and cisplatin as first-line therapy for small-cell lung cancer". J Clin Oncol. 3 (11): 1471–7. PMID 2997406.
  8. Okamoto H, Watanabe K, Nishiwaki Y, Mori K, Kurita Y, Hayashi I; et al. (1999). "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. 17 (11): 3540–5. PMID 10550152.
  9. Noda K, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A; et al. (2002). "Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer". N Engl J Med. 346 (2): 85–91. doi:10.1056/NEJMoa003034. PMID 11784874.
  10. Hanna N, Bunn PA, Langer C, Einhorn L, Guthrie T, Beck T; et al. (2006). "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. 24 (13): 2038–43. doi:10.1200/JCO.2005.04.8595. PMID 16648503.
  11. Schmittel A, Fischer von Weikersthal L, Sebastian M, Martus P, Schulze K, Hortig P; et al. (2006). "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. 17 (4): 663–7. doi:10.1093/annonc/mdj137. PMID 16423848.


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