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 ...
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Chapter 085. Neoplasms of the Lung (Part 16) Chapter 085. Neoplasms of the Lung (Part 16) Chemotherapy Chemotherapy palliates symptoms, improves the quality of life, andimproves survival in newly diagnosed patients with stage IV NSCLC, particularlyin patients with good performance status. Whereas the median survival foruntreated patients is roughly 4–6 months, and 1-year survival is 5–10%, withcombination chemotherapy the median survival is 8–10 months, 1-year survival is30–35%, and 2-year survival 10–15%. Combination chemotherapy produces anobjective tumor response in 20–30% of patients, although the response is completein Chemotherapy for previously untreated, good-performance-status patientstypically consists of two drugs (doublets). Traditionally, one of the two drugshas been either cisplatin or carboplatin, and the other drug is a taxane (paclitaxelor docetaxel), gemcitabine, or a vinca alkaloid such as vinorelbine. No majordifference in outcome has been observed between the standard chemotherapydoublets, although they differ in terms of schedule, side effects, and cost.Cytotoxic chemotherapy for first-line chemotherapy is typically administered forfour to six cycles; no benefit has been shown for continuing the samechemotherapy beyond that point. After four to six cycles, chemotherapy is usuallystopped and the patient observed closely for tumor progression, at which pointsecond-line chemotherapy may be started if the patients performance statusremains good. Nausea with typical first-line regimens is usually mild, particularlywhen 5-HT3 serotonin antagonists are used as antiemetics. Hair loss depends onthe choice of regimen and should be discussed with the patient. All regimens causemyelosuppression, but the incidence of neutropenic fevers, bleeding episodes, oranemia requiring transfusions is low. Growth-factor support is rarely needed.Elderly patients without significant comorbid conditions benefit from and toleratechemotherapy much the same as their younger counterparts. However, patientswith a poorer performance status seem to obtain less benefit. Docetaxel and pemetrexed are second-line agents for patients who haveprogressive disease on first-line chemotherapy and still have a good performancestatus. Docetaxel improves progression-free survival and overall survivalcompared to best supportive care, and pemetrexed has roughly the same efficacyas 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 diseasewhen combined with chemotherapy (paclitaxel/carboplatin). Median, 1-year, and2-year survival in response to chemotherapy plus bevacizumab was 12.3 months,51%, and 23%, compared, respectively, to 10.3 months, 44%, and 15% withchemotherapy alone (hazard ratio 0.79, p = 0.003). A 1-year survival of >50% anda 2-year survival of >20% represents a significant improvement in long-termprognosis. The dose of bevacizumab administered on this trial was 15 mg/kg IVevery 3 weeks. Bevacizumab side effects include bleeding, hypertension, andproteinuria, and the hemorrhagic side effects make this agent risky to use. Patientswith squamous cancer cannot receive bevacizumab because of their tendencytoward serious hemorrhagic side effects. Patients with brain metastases,hemoptysis, and bleeding disorders or who need anticoagulation are also noteligible to receive the agent. Despite these restrictions and careful patientselection, 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- andthird-line therapy of NSCLC. Clinical responses have been seen in a large fractionof the small subset of patients with tumors bearing mutations in the EGFR.Prolonged survival with EGFR TKI treatment has also been observed in somepatients whose tumors have amplification of the EGFR gene or overexpression ofthe receptor. Side effects of erlotinib differ from chemotherapy side effects of hairloss, nausea, and neutropenia, but they include acneiform skin rash and diarrhea.For patients whose tumors respond to EGFR TKI therapy, substantial clinicalbenefit is seen. Small Cell Lung Cancer SCLC is a chemotherapy-sensitive disease. Patients with limited stagedisease 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 ...