In Chemotherapy for Lung Cancer, Sometimes Less is More
Authors: Eric Roeland, Charles Loprinzi, Timothy J. Moynihan, Thomas J. Smith, Jennifer Temel
Journal: Journal of the National Comprehensive Cancer Network (2013)

Chemotherapy remains the backbone of care for patients with metastatic cancer and provides increasing hope for patients and their families as novel drug targets and therapeutic agents are discovered.Over the past decade, the therapeutic arsenal has markedly expanded, from nitrogen mustard and folic acid antagonists of the mid-20th century to the targeted regimens of "personalized" medicine today.In patients with metastatic disease, chemotherapy can slow disease progression, leading to prolonged survival, and palliate symptoms.Lung cancer remains the leading cause of cancerrelated mortality in the United States because of both the high prevalence of advanced disease at diagnosis and the low rate of cure of early-stage disease.Thus, many patients with metastatic non-small cell lung cancer (NSCLC) receive chemotherapy with the goal of prolonging life, relieving symptoms, and improving quality of life (QOL).Although chemotherapy can achieve these goals in selected patients with metastatic NSCLC and a good performance status (PS), it has a limited role in patients whose cancer has progressed through multiple lines of therapy and those with a poor PS (eg, ECOG 3 or 4).The response rates for patients with metastatic NSCLC treated with both a platinum and a taxane have been reported to be only 2% for third-line and 0% for fourth-line chemotherapy, 1 which is insufficient to provide a significant survival benefit. 2 Data regarding patients with NSCLC with a PS of 2 remains an unsolved issue, and carefully designed phase III trials are necessary to better define optimal treatment for patients with a borderline PS. [3][4][5] Thus, ASCO and NCCN guidelines have concluded that patients with a PS greater than 3 do not benefit from chemotherapy, except erlotinib for epidermal growth factor receptor mutation-positive patients and crizotinib for ALK-positive patients. 6-8Despite these published national guidelines, the current trend is for patients with metastatic NSCLC to receive multiple lines of chemotherapy, even in the face of a declining or poor PS. [9][10][11][12] The continued discoveries of novel, targeted therapies are making it increasingly more challenging for patients and oncologists to forgo additional treatment, because of the hope of finding one that will lead to long-term progression-free survival.We all hope that the next erlotinib or crizotinib is on the horizon and that we will have effective targeted therapies available for all patients with metastatic NSCLC.This hope makes it difficult for oncologists to not offer that "one additional treatment" when faced with a patient whose condition is declining.However, the downside to this eternal optimism is that patients may receive additional lines of therapy with no clear benefit and with real potential harm.Although data have not conclusively demonstrated that prolonged chemotherapy may truly harm or even decrease survival in patients with metastatic cancer, one study examining Medicare patients with congestive heart failure or any 1 of 5 different malignancies supported the theory that hospice referral led to an improved survival, 13 and another study examining continued chemotherapy to the premortem period suggested that it only delays hospice referral and does not improve survival. 14 recently conducted prospective, randomized, single-institution clinical trial provides important insight into the question of prolonged chemotherapy administration in patients with incurable NSCLC. 15In this study, 151 patients with