ES 09.02 Cytotoxic Chemotherapy

Abstract

Untreated small-cell lung cancer (SCLC) is highly sensitive to both chemotherapy and radiotherapy, although its growth is very rapid. Clinically, SCLC is classified into limited-diseases (LD) and extensive-disease (ED). Although there is no distinct criteria, LD is generally accepted to be a disease which is confined to the hemithorax of origin, the mediastinum, or the supraclavicular lymph nodes without malignant effusion, i.e., a disease that curative radiotherapy is applicable. Nearly 30% of SCLC is LD at initial diagnosis. LD-SCLC is potentially curable disease, and standard treatment is chemo-radiotherapy, especially concurrent use of chemotherapy and radiotherapy is chosen if performance status of patient is 2 or less and organ function is good. Cisplatin plus etoposide is usually administered together with radiotherapy, since the combination chemotherapy is one of the most effective regimens and also risk of radiation pneumonia is low when the combination is chosen. Median survival time of LD-SCLC is 16 to 24 months and 5-year survival is nearly 15%. On the other hand, median survival time of ED-SCLC is 6-12 months, and long-term disease-free survival is rare. Chemotherapy alone is chosen to ED-SCLC. Globally, combination of cisplatin/carboplatin plus etoposide is recognized as a standard chemotherapy. In Japanese guideline, a combination with cisplatin plus irinotecan is the first choice if tolerable. One of the reasons why standard therapy is different between western and eastern countries is based on distribution of uridine diphosphate glucuronosyltransferase (UGT) 1A1 gene polymorphisms. Although drug therapy with cytotoxic agents to SCLC used be the only successful treatment modality for metastatic lung cancer in the past century, its development now appears to slow down. To maximize the effect of cytotoxic agents, combination with immune checkpoint inhibitors or novel targeted drugs would be critical. cytotoxic drug, chemoradiotherapy, UGT 1A1