Small Cell Lung Cancer Treatment Protocols 

Updated: May 04, 2020
  • Author: Marvaretta M Stevenson, MD; Chief Editor: Nagla Abdel Karim, MD, PhD  more...
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Treatment Protocols

Treatment protocols for small cell lung cancer (SCLC) are provided below, including the following:

  • First-line therapy
  • Therapy for limited-stage disease
  • Therapy for extensive-stage disease

Treatment recommendations for limited-stage SCLC

Stages I-III disease:

  • Limited-stage disease is typically treated with systemic therapy, with or without radiation therapy. [1]

  • Chemotherapy and radiation therapy are typically given concurrently, but can also be given sequentially for limited-stage disease in 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]

  • A select group of patients may be eligible for surgical resection. Clinical stage I - IIA (T1 - 2, N0, M0) patients who are surgical candidates should undergo pathological mediastinal staging to determine whether there is medastinal lymph node involvement.

  • Patients with pathologically negative medastinal lymph nodes should go on to lobectomy with mediastinal lymph node dissection or sampling.

  • Patients found to have pN0 disease at the time of surgical resection should receive adjuvant systemic therapy (see options below).

  • Patients found to have pN1 or pN2 disease should receive systemic therapy with or without mediastinal radiation therapy.

Concurrent chemotherapy recommendationswith radiation for limited-stage disease:

  • Cisplatin 60 mg/m2 IV on day 1 plus etoposide 120 mg/m2 IV on days 1-3 every 21-28d [3, 1]

  • Cisplatin 75 - 80 mg/m2 IV on day 1 plus  etoposide 100 mg/m2 IV on days 1-3 every 21-28d [4, 1]

  • Cisplatin 25 mg/m2 IV on days 1 - 3 plus  etoposide 100 mg/m2 IV on days 1-3 every 21-28d  [1]

  • Carboplatin area under the curve (AUC) 5-6 IV day 1 plus  etoposide 100 mg/m2 IV days 1-3 every 21-28d [5, 1]

  • Chemotherapy should be given up to four to six cycles.

  • 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 [3, 4] or

  • Carboplatin AUC 5-6 IV on day 1 plus  etoposide 80-100 mg/m2 IV on days 1-3 every 28d [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 four to six cycles:

  • Atezolizumab 1200 mg IV on day 1 plus  carboplatin AUC 5 on day 1 plus  etoposide 100 mg/m2 IV on days 1-3 every 21d x four cycles; follow with maintenance atezolizumab every 21d [7]

  • Durvalumab 1500 mg IV on day 1 plus  etoposide 80-100 mg/m2 IV on days 1-3 plus  carboplatin AUC 5 or 6 on day 1 or cisplatin 75-80 mg/m2 every 21d x four cycles; follow with maintenance atezolizumab every 21d [8]

  • Cisplatin 60-80 mg/m2 IV on day 1 plus  etoposide 80-120 mg/m2 IV on days 1-3 every 21-28d [9, 10, 11, 12, 13, 14, 15, 16]

  • Carboplatin AUC 5-6 IV on day 1 plus  etoposide 80-100 mg/m2 IV on days 1-3 every 28d [16, 17, 18, 19]

  • Cisplatin 60 mg/m2 IV on day 1 plus irinotecan 60 mg/m2 IV on days 1, 8, and 15 every 28d [11, 14, 15]

  • 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 [10, 12]

  • Carboplatin AUC 5 IV on day 1 plus  irinotecan 50 mg/m2 IV on days 1, 8, and 15 every 28d [17, 19]

  • Carboplatin AUC 4-5 IV on day 1 plus  irinotecan 150-200 mg/m2 IV on day 1 every 21d [20, 21, 22]

  • Cisplatin 25 mg/m2 IV on days 1 - 3 plus  etoposide 100 mg/m2 IV on days 1-3 every 21-28d  [1]

  • 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 [23, 24, 25]

Second-line chemotherapy for relapsed or refractory disease

Stage IV disease [10] :

  • 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 an expected response rate of 62-100% [2, 1]

Systemic therapy recommendationsfor relapsed or refractory SCLC:

  • Etoposide 50 mg/m2 PO daily for 3wk every 4wk [26]

  • Topotecan 2.3 mg/m2 PO on days 1-5 every 21d [27, 28, 29]

  • Topotecan 1.5 mg/m2 IV on days 1-5 every 21d [27, 28, 30]

  • Carboplatin AUC 5 IV on day 1 plus  irinotecan 50 mg/m2 IV on days 1, 8, and 15 every 28d [17, 19]

  • Carboplatin AUC 4 - 5 IV on day 1 plus  irinotecan 150-200 mg/m2 IV on day 1 every 21d [20, 21, 22]

  • 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 [31]

  • Cisplatin 60 mg/m2 IV on day 1 plus  irinotecan 60 mg/m2 IV on days 1, 8, and 15 every 28d [11, 15]

  • 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 [10, 12]

  • Paclitaxel 80 mg/m2 IV weekly for 6wk every 8wk [32]

  • Paclitaxel 175 mg/m2 IV on day 1 every 3wk [33]

  • 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 [1]

  • Pembrolizumab 200 mg IV every 3 weeks or 400 mg IV every 6 weeks until disease progression [34, 35]

  • Nivolumab 240 mg IV every 2wk or nivolumab 480 mg IV every 4 wk until disease progression [36, 1, 37]

  • Nivolumab 1 mg/kg IV plus ipilimumab 3 mg/kg IV every 21 days for 4 cycles followed by nivolumab maintenance (240 mg IV every 2wk or nivolumab 480 mg IV every 4 wk) [1, 36, 37]

  • Institution Review Board (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]

  • Thoracic radiation therapy should be considered for patients with extensive stage disease after they complete systemic therapy. [1]

  • 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, because chemotherapy produces high response rates. [1, 2]

  • 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. [38]