Updated January 2014
Extensive Stage SCLC
The prognosis for most cases of extensive stage SCLC is guarded and treatment is palliative. Without chemotherapy, the average survival is only 8-10 weeks. Thoracic radiotherapy alone may palliate local symptoms but has little impact on survival. The majority of patients (70-80%) respond to chemotherapy and complete responses occur in 15-20%. Median survival with standard regimens is 8-11 months. Prophylactic cranial irradiation in patients responding to chemotherapy extends survival (Slotman 2007). Almost all patients relapse and only 5-10% are alive at 2 years. The small proportion (1-2%) of long-term survivors usually had low bulk metastatic disease and an exceptional response to chemotherapy.
Standard Chemotherapy of Extensive Stage SCLC
Guideline: Combination chemotherapy is superior to monotherapy in SCLC.
Level of Evidence: I
Monotherapy with oral etoposide has been proved inferior to combination chemotherapy in SCLC (Souhami, 1997). Combination chemotherapy should be recommended to all extensive SCLC patients fit enough to receive it. However, randomized trials of various combination chemotherapy protocols have not demonstrated a superior regimen.
Standard regimens are the same as for limited SCLC (see above 6.4.2.1) including four cycles of sequential platinum plus etoposide (Protocol LUSCPE). Carboplatin-based chemotherapy appears iso-effective compared to cisplatin-based chemotherapy in a meta-analysis (Rossi 2012).
Although cyclophosphamide and doxorubicin regiments (LUSCCAV) perform as well as platinum and etoposide in the extensive stage setting, six cycles of non-platinum containing chemotherapy appear required to generate a similar result (Roth).
A recent meta-analysis of seven randomized studies showed similar results with irinotecan-platinum compared to etoposide-cisplatin. Irinotecan led to more gastrointestinal toxic effects while more hematological toxic effects were observed with etoposide (Shao 2012). Etoposide and platinum remains the standard of care for first line treatment of advanced non-small cell lung cancer suitable for combination chemotherapy.
Frail or elderly patients that are judged unsuitable for intravenous combination chemotherapy or refuse such therapy may derive some palliative benefit from oral etoposide (LUSCPOE).
References:
Souhami RL, Spiro SG, Rudd RM et al: Five day oral etoposide treatment for advanced small-cell lung cancer: randomized comparison with intravenous chemotherapy. J Natl Cancer Inst 89:577-80, 1997.
Rossi A, Di Maio M, Chiodini P, et al. Carboplatin or cisplatin-based chemotherapy in first-line treatment of small-cell lung cancer: the COCIS meta-analysis of individual patient data. J Clin Oncol 30:1692-1698, 2012
Roth B, Johnson D, Einhorn L, et al. Randomized study of cyclophosphamide, doxorubicin and vincristine versus etoposide and cisplatin versus alternation of these two regimens in extensive small cell lung cancer: A phase III trial of the Southeastern Cancer Study Group. J Clin Oncol 10:282-291, 1992.
Shao N, Jin S, Zhu W. An updated meta-analysis of randomized controlled trials comparing irinotecan/platinum with etoposide/platinum in patients with previously untreated extensive stage small cell lung cancer. J Thoracic Oncol 7:470-472, 2012
Radiotherapy for Extensive Stage SCLC
Thoracic irradiation is not routinely recommended for patients with extensive stage SCLC that achieve satisfactory palliation with chemotherapy. Integrated chemoradiation may be used for selected patients with equivocal, minimal or "regional" extensive stage (pleural effusion, contralateral supraclavicular nodes, cervical nodes).
Palliative thoracic irradiation after palliative chemotherapy for extensive stage SCLC is indicated for regional disease that is symptomatic. Additionally, if the original local disease was bulky, the cancer is likely to progress first at that site. Palliative radiotherapy to local disease after response to chemotherapy is reasonable particularly if the patient resides at a region remote from a radiotherapy facility. It may prolong time to progression but has no proven effect on overall survival.
Guideline: Prophylactic cranial irradiation for extensive stage small cell lung cancer with response to chemotherapy decreases the risk of brain metastases and prolongs survival.
Level of Evidence: 2
One randomized trial in extensive stage SCLC responding to induction chemotherapy showed PCI to cause an impressive reduction in symptomatic brain metastases, with a hazard ratio of 0.27 (p<0.001). Overall survival was also improved (HR 0.68, p=0.003) with PCI with a 1-year survival from time of randomization of 27.1% in the treated group and 13.3% in the untreated group (Slotman). PCI radiotherapy dose in extensive SCLC responders is 25 Gy in 10 fractions or 20 Gy in 5 fractions.
Patients with brain metastases have traditionally received therapeutic brain irradiation followed by chemotherapy but it is now clear that brain metastases respond to chemotherapy and good performance status patients can be palliated with chemotherapy followed by therapeutic brain irradiation. Urgent therapeutic brain irradiation is recommended for rapidly evolving or more severe neurological deficits.
Palliative radiotherapy for locally advanced or metastatic SCLC is guided by the same principles as NSCLC (see above 6.4.1).
Reference:
1. Slotman B, Faivre-Finn C, Kramer G, et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 357:664-72, 2007
