CHEMOTHERAPY FOR METASTATIC SMALL CELL LUNG CANCER
A 62-year-old Caucasian male with an 80 pack-year smoking history, chronic obstructive pulmonary disease (COPD), and diabetes presents with progressively worsening shortness of breath over the past week. He is saturating 86% on room air in the emergency room, requiring oxygen at 5 L per nasal cannula and eventually bilevel positive airway pressure (BiPAP). Examination of the arterial blood gas (ABG) shows he is hypoxic and hypercapnic. His breathing becomes more labored, and he is electively intubated. Chest computed tomography (CT) shows bilateral pulmonary nodules with bulky mediastinal and hilar adenopathy. Abdominal/pelvic CT shows multiple hepatic lesions. Brain magnetic resonance imaging (MRI) is negative for brain metastases. Biopsy of a liver lesion returns with presence of small cell carcinoma.
When should you expect to see a response in small cell lung cancer (SCLC)?
What is a common chemotherapy regimen for SCLC?
What is the recommended first line treatment for extensive stage SCLC?
As with early stage SCLC, metastatic SCLC also has a dramatic response initially, with response rates of 60%-70% with chemotherapy alone. However, even with appropriate treatment, the median survival rates are only 9-11 months, and the 2-year survival rate is less than 5% in these patients.1
Small cell lung cancer is very sensitive to chemotherapy and often has a dramatic response within 1-2 cycles.
Many chemotherapy combinations have been evaluated for extensive stage SCLC, but none has had consistent benefit when compared to cisplatin/etoposide. A Japanese phase 3 trial showed promising results, with 154 patients randomized to either cisplatin/irinotecan or cisplatin/etoposide.2 Those treated with cisplatin and irinotecan had a significantly better overall response rate (84.4% vs. 67.5%), median survival (12.8 months vs. 9.4 months), and 1-year survival (58.4% vs. 37.7%) compared to those treated with cisplatin and etoposide, respectively. The irinotecan arm had more grade 3 and 4 diarrhea, while the etoposide arm had higher rates of myelosuppression.
The Southwest Oncology Group (SWOG) tried replicating the trial using the same schema but failed to show a significant difference in response rate or overall survival.3 However, another phase 3 trial involving 220 patients did find that median overall survival was slightly improved (8.5 months vs. 7.1 months, p = .04) with carboplatin/irinotecan compared to carboplatin/oral etoposide.4 A meta-analysis went on to suggest improved progression-free survival and overall survival with irinotecan plus a platinum drug when compared to etoposide with a platinum drug, but this meta-analysis did not use individual data, and the small absolute survival benefit needed to be balanced with toxicities from irinotecan.5 Based on these findings, the National Comprehensive Cancer Network (NCCN) guidelines consider carboplatin and irinotecan as an option for extensive-stage SCLC but continue to recommend etoposide plus platinum regimens.
The standard doublet for small cell lung cancer is ...