Chapter 085. Neoplasms of the Lung (Part 16)

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Chemotherapy Chemotherapy palliates symptoms, improves the quality of life, and improves survival in newly diagnosed patients with stage IV NSCLC, particularly in patients with good performance status. Whereas the median survival for untreated patients is roughly 4–6 months, and 1-year survival is 5–10%, with combination chemotherapy the median survival is 8–10 months, 1-year survival is 30–35%, and 2-year survival 10–15%. Combination chemotherapy produces an objective tumor response in 20–30% of patients, although the response is complete in ...

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Chapter 085. Neoplasms of the Lung (Part 16) Chemotherapy Chemotherapy palliates symptoms, improves the quality of life, and improves survival in newly diagnosed patients with stage IV NSCLC, particularly in patients with good performance status. Whereas the median survival for untreated patients is roughly 4–6 months, and 1-year survival is 5–10%, with combination chemotherapy the median survival is 8–10 months, 1-year survival is 30–35%, and 2-year survival 10–15%. Combination chemotherapy produces an objective tumor response in 20–30% of patients, although the response is complete in
Chemotherapy for previously untreated, good-performance-status patients typically consists of two drugs ("doublets"). Traditionally, one of the two drugs has been either cisplatin or carboplatin, and the other drug is a taxane (paclitaxel or docetaxel), gemcitabine, or a vinca alkaloid such as vinorelbine. No major difference in outcome has been observed between the standard chemotherapy doublets, although they differ in terms of schedule, side effects, and cost. Cytotoxic chemotherapy for first-line chemotherapy is typically administered for four to six cycles; no benefit has been shown for continuing the same chemotherapy beyond that point. After four to six cycles, chemotherapy is usually stopped and the patient observed closely for tumor progression, at which point second-line chemotherapy may be started if the patient's performance status remains good. Nausea with typical first-line regimens is usually mild, particularly when 5-HT3 serotonin antagonists are used as antiemetics. Hair loss depends on the choice of regimen and should be discussed with the patient. All regimens cause myelosuppression, but the incidence of neutropenic fevers, bleeding episodes, or anemia requiring transfusions is low. Growth-factor support is rarely needed. Elderly patients without significant comorbid conditions benefit from and tolerate chemotherapy much the same as their younger counterparts. However, patients with a poorer performance status seem to obtain less benefit. Docetaxel and pemetrexed are second-line agents for patients who have progressive disease on first-line chemotherapy and still have a good performance
status. Docetaxel improves progression-free survival and overall survival compared to best supportive care, and pemetrexed has roughly the same efficacy as docetaxel, but with fewer side effects. VEGF Targeted Therapy Bevacizumab, a monoclonal antibody to VEGF, improves response rate, progression-free survival, and overall survival of patients with advanced disease when combined with chemotherapy (paclitaxel/carboplatin). Median, 1-year, and 2-year survival in response to chemotherapy plus bevacizumab was 12.3 months, 51%, and 23%, compared, respectively, to 10.3 months, 44%, and 15% with chemotherapy alone (hazard ratio 0.79, p = 0.003). A 1-year survival of >50% and a 2-year survival of >20% represents a significant improvement in long-term prognosis. The dose of bevacizumab administered on this trial was 15 mg/kg IV every 3 weeks. Bevacizumab side effects include bleeding, hypertension, and proteinuria, and the hemorrhagic side effects make this agent risky to use. Patients with squamous cancer cannot receive bevacizumab because of their tendency toward serious hemorrhagic side effects. Patients with brain metastases, hemoptysis, and bleeding disorders or who need anticoagulation are also not eligible to receive the agent. Despite these restrictions and careful patient selection, significant bleeding is noted in about 4% of patients. EGFR Targeted Therapy
Erlotinib is an oral inhibitor of the EGFR kinase that is used in second- and third-line therapy of NSCLC. Clinical responses have been seen in a large fraction of the small subset of patients with tumors bearing mutations in the EGFR. Prolonged survival with EGFR TKI treatment has also been observed in some patients whose tumors have amplification of the EGFR gene or overexpression of the receptor. Side effects of erlotinib differ from chemotherapy side effects of hair loss, nausea, and neutropenia, but they include acneiform skin rash and diarrhea. For patients whose tumors respond to EGFR TKI therapy, substantial clinical benefit is seen. Small Cell Lung Cancer SCLC is a chemotherapy-sensitive disease. Patients with limited stage disease have high response rates (60–80%) and a 10–30% complete response rate. The response rates in patients with extensive disease are somewhat lower (50%) and almost always partial responses. Tumor regressions usually occur quickly, within the first two cycles of treatment, and provide rapid palliation of tumor- related symptoms. Chemotherapy significantly prolongs survival. Untreated, patients with limited-stage SCLC have a median survival of 12 weeks; the median survival with chemotherapy is 18 months, and long-term (>3 year) survival is 30–40%. The median survival of extensive-stage patients is 9 months;
years. Thus, although initially responsive, most patients with SCLC relapse, presumably due to the emergence of chemotherapy resistance.