Hematology/oncology clinics of North America
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Hematol. Oncol. Clin. North Am. · Feb 2004
ReviewRadiotherapy and chemotherapy in locally advanced non-small cell lung cancer: preclinical and early clinical data.
Over the past 20 years, combined treatment with radiotherapy and second-generation chemotherapy drugs was extensively studied in patients with locally advanced NSCLC and became the standard over radiotherapy alone in patients with good performance status. Radiosensitizing properties of cisplatin have been identified in the laboratory. Close temporal administration of cisplatin and radiation is mandatory for enhanced antitumor efficacy, but results in significant toxicity to normal tissues. ⋯ The respective benefits of either induction or consolidation full-dose chemotherapy with these drugs, before or after concurrent chemoradiotherapy with second- or third-generation chemotherapy, are presently being evaluated in phase III studies. As a result of improved survival and enhanced local control, most of these studies show a significant increase in the incidence of brain metastases. Because the brain is often the first site of relapse after concurrent chemoradiotherapy with or without surgery, the issue of prophylactic cranial irradiation is currently being addressed in a phase III trial.
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All of the third-generation chemotherapeutic agents reviewed in this article are independently active against NSCLC, although the agents differ significantly in their cellular and molecular mechanisms of cytotoxicity. All have also been shown to potentiate radiation effects, and thus are promising in exerting further cytotoxicity when used in combination chemoradiation therapy for locally advanced NSCLC. Although the toxicity to normal tissue varies among these agents when used alone, phase I/II clinical results consistently demonstrated higher risk and severity of esophagitis and pneumonitis when these agents were administered concurrently with thoracic radiation. ⋯ Although direct statistical comparison between the treatment arms was not valid for a phase II setting, such an analysis did indeed reveal similar overall response rates for these three arms. Chemoradiation using third-generation chemotherapeutic agents has improved local tumor response rates, with enhanced radiation toxicity such as esophagitis and pneumonitis. The challenge of targeting distant disease control for locally advanced NSCLC continues.