NCCN's new lung cancer guidelines called a useful reference

February 11, 2008

NCCN's new guidelines for nonsmall cell lung cancer contain new recommendations relating to drug therapy.

The National Comprehensive Cancer Network (NCCN) has recently updated its non-small cell lung cancer (NSCLC) guidelines.

The updated NSCLC guidelines provide information on additional cisplatin-based postoperative adjuvant chemotherapy regimens. Results from recent studies on adjuvant chemotherapy have shown favorable results with cisplatin-based regimens. The International Adjuvant Lung Cancer Trial (IALT) reported a statistically significant survival benefit with cisplatin-based adjuvant therapy compared with observation at a median of 56 months in patients with completely resected NSCLC. Patients who received the cisplatin-based regimen demonstrated a significantly higher survival rate (44.5% vs. 40.4%) and disease-free survival (39.4% vs. 34.3%). The NCCN panel has also included cisplatin combined with vinorelbine, vinblastine, or etoposide as adjuvant chemotherapy regimens. The guidelines provide alternative treatments which are mainly carboplatin-based regimens for patients with comorbidities or who are unable to tolerate cisplatin.

Another update to the guidelines involves the use of molecular markers to individualize therapy for patients. "Patients receiving individualized therapy will hopefully get more benefit and experience less unnecessary toxicity from medications that may not work in treating NSCLC," added Cooper. Pathologic evaluation is performed to determine the molecular abnormalities of lung cancer that may be able to predict sensitivity and resistance to epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKI). Epidermal growth factor receptor (EGFR) is often over expressed in various malignancies. There is a significant association between EGFR and response to tyrosine kinase inhibitors (TKI). K-ras is an effector of the EGFR pathway that has been found mutated in approximately 15%-30% of lung adenocarcinomas and to be associated with tobacco smoke exposure. K-ras mutations are associated with intrinsic TKI resistance. Therefore gene sequencing may be useful for selecting patients who may benefit from TKI therapy.

NCSLC patients who have never smoked and whose tumors contain an EGFR mutation will respond to TKI therapy such as erlotinib (Tarceva, Genentech/OSI). Thus, the NCCN guidelines now state that erlotinib may be used with or without chemotherapy as a first-line agent in patients with advanced disease who have never smoked and whose tumors have a known EGFR mutation or gene amplification. "Learning where therapies like erlotinib will be beneficial to patients will be important in the future," stated Rowena Schwartz, Pharm.D., and pharmacy director at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore, Md. Erlotinib was approved in 2004 by the Food & Drug Administration for the treatment of patients with locally advanced or metastatic NSCLC after failure of at least one chemotherapeutic regimen.

"These guidelines are extremely beneficial to pharmacists because we often use them as a reference and to determine where therapies fit in the treatment spectrum," concluded Schwartz.

THE AUTHOR is a writer based in New Jersey.