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    Small Cell Lung Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Extensive-Stage Small Cell Lung Cancer Treatment

    Standard Treatment Options for Patients With Extensive-Stage Small Cell Lung Cancer (SCLC)

    Standard treatment options for patients with extensive-stage SCLC include the following:

    1. Combination chemotherapy.
    2. Radiation therapy.
    3. Prophylactic cranial irradiation.

    Combination chemotherapy

    Chemotherapy for patients with extensive-stage disease (ED) SCLC is commonly given as a two-drug combination of platinum and etoposide in doses associated with at least moderate toxic effects (as in limited-stage [LD] SCLC).[1] Cisplatin is associated with significant toxic effects and requires fluid hydration, which can be problematic in patients with cardiovascular disease. Carboplatin is active in SCLC, is dosed according to renal function, and is associated with less nonhematological toxic effects.

    Other regimens appear to produce similar survival outcomes but have been studied less extensively or are in less common use.

    Table 2. Combination Chemotherapy For Extensive-Stage Small Cell Lung Cancer

    Standard treatment Etoposide + cisplatin
    Etoposide + carboplatin
    Other regimens Cisplatin + irinotecan
    Ifosfamide + cisplatin + etoposide
    Cyclophosphamide + doxorubicin + etoposide
    Cyclophosphamide + doxorubicin + etoposide + vincristine
    Cyclophosphamide + etoposide + vincristine
    Cyclophosphamide + doxorubicin + vincristine

    Doses and schedules used in current programs yield overall response rates of 50% to 80% and complete response rates of 0% to 30% in patients with ED.[2,3][Level of evidence: 1iiA]

    Intracranial metastases from small cell carcinoma may respond to chemotherapy as readily as metastases in other organs.[4,5]

    Evidence (standard regimens):

    1. Two meta-analyses evaluating the role of platinum combinations versus nonplatinum combinations have been published.
      • A Cochrane analysis did not identify a difference in 6-, 12-, or 24-month survival.[6]
      • A meta-analysis of 19 trials published between 1981 and 1999 showed a significant survival advantage for patients receiving platinum-based chemotherapy compared with those not receiving a platinum agent.[3][Level of evidence: 1iiA]
    2. The Hellenic Oncology Group conducted a phase III trial comparing cisplatin and etoposide with carboplatin plus etoposide.[7] The median survival was 11.8 months in the cisplatin arm and 12.5 months in carboplatin-treated patients.[7][Level of evidence: 1iiA] Although this difference was not statistically significant, the trial was underpowered to prove equivalence of the two treatment regimens in patients with either LD or ED.

    Evidence (other combination chemotherapy regimens):

    1. Irinotecan. Five trials and two meta-analyses have evaluated the combination of etoposide and cisplatin versus irinotecan and cisplatin. Only one of the trials showed the superiority of the irinotecan and cisplatin combination.[8][Level of evidence: 1iiA] Subsequent trials and the meta-analyses support that the regimens provide equivalent clinical benefit with differing toxicity profiles.[9,10,11,12,13,14][Level of evidence: 1iiA] Irinotecan and cisplatin regimens led to less grade 3 to 4 anemia, neutropenia, and thrombocytopenia but more grade 3 to 4 vomiting and diarrhea than etoposide and cisplatin regimens. Treatment-related deaths were comparable between the two groups.
    2. Topotecan. In a randomized trial of 784 patients, the combination of oral topotecan given with cisplatin for 5 days was not found to be superior to etoposide and cisplatin.[15] The 1-year survival rate was 31% (95% confidence interval [CI], 27%-36%) and was deemed to be noninferior, as the difference of -0.03 met the predefined criteria of no more than 10% absolute difference in 1-year survival.[15][Level of evidence: 1iiA]
    3. Paclitaxel. No consistent survival benefit has resulted from the addition of paclitaxel to etoposide and cisplatin.[16,17]
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