Small Cell Lung Cancer Treatment Protocols 

Updated: Mar 23, 2021
Author: Marvaretta M Stevenson, MD; Chief Editor: Nagla Abdel Karim, MD, PhD 

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 plusetoposide 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 (if patient’s body weight ≤30 kg, dose at 20 mg/kg 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 durvalumab 1500 mg IV every 28 days (if patient’s body weight ≤30kg, dose at 10 mg/kg every 14 days until weight >30 kg); continue until disease progression or unacceptable toxicity[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 plusirinotecan 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 plusdoxorubicin 40-50 mg/m2 IV on day 1 plusvincristine 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 plusdoxorubicin 40-50 mg/m2 IV on day 1 plusvincristine 1-1.4 mg/m2 IV on day 1 every 21-28d[1]

  • Lurbinectedin 3.2 mg/m2 IV every 21 days until disease progression or unacceptable toxicity[36]

  • 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.[37]

  • Two monoclonal antibodies to programmed cell death–1 protein (PD-1) had been granted accelerated approval for treatment of metastatic SCLC in patients with progression after platinum-based chemotherapy and at least 1 other line of therapy—nivolumab in 2018 and pembrolizumab in 2020. However, in 2021, this indication was voluntarily withdrawn from the US market for both agents, after further study failed to confirm significant improvement in overall survival.[38, 39]