Treatment Paradigms for Patients with Metastatic Non-Small-Cell Lung Cancer: First-, Second-, and Third-Line

Abstract

Treatment paradigms for patients with metastatic non-small-cell lung cancer: first-, second-, and third-line Curr Oncol, Vol. 19, pp. S52-S58; doi: http://dx.doi.org/10.3747/co.19.1114 ABSTRACT Metastatic non-small-cell lung cancer (nsclc) is the leading cause of cancer mortality in Canada. Although treatment outcomes in advanced disease remain modest, with paradigm shifts in the approach to treatment, they are steadily improving. Customizing treatment based on histology and molecular typing has become the standard of care. EGFR genotyping and pathology subtyping should be considered routine in new diagnoses of metastatic nsclc. Treatment options for those with somatic EGFR activating mutations include gefitinib until progression, followed by standard chemotherapy. For patients with wild-type EGFR, or in patients whose EGFR genotype is unknown, platinum-based chemotherapy remains the firstline standard, with single-agent chemotherapy as an option for older patients and those who are unfit for platinum-doublet therapy. Patients with nonsquamous histology may receive treatment regimens incorporating pemetrexed or bevacizumab. In patients with squamous cell carcinoma, the latter agents should be avoided because of concerns about enhanced toxicity or decreased efficacy. Secondline chemotherapy is offered to a selected subgroup of patients upon progression and may include pemetrexed in non-squamous histology and docetaxel or erlotinib (or both) in all histologies. Currently, only erlotinib is offered as a third-line option in unselected nsclc patients after failure of first-and second-line chemotherapy. Maintenance therapy is emerging as a new option for patients, as are targeted therapies for particular molecular subtypes of nsclc, such as crizotinib in tumours harbouring the EML4-ALK gene rearrangement. KEY WORDSMetastatic non-small-cell lung cancer, nsclc, advanced, systemic therapy, chemotherapy INTRODUCTIONAt more than 25,000 new cases, lung cancer remains the most commonly diagnosed cancer among Canadians (excluding non-melanoma skin cancer); it also causes the greatest number of cancer-related deaths (more than 20,000 deaths per year) 1 . As well, more than half the Canadians diagnosed with lung cancer present with metastatic disease. Most lung cancer patients, approximately 85%, have non-small-cell lung cancer (nsclc). Of those, approximately 40%-60% have adenocarcinoma histology; 10%-15%, squamous histology; 5%, neuroendocrine histology; and the rest, "not otherwise specified" 2,3 .Survival is short in the setting of advanced nsclc, a median of 4-6 months, and more than 80% patients have multiple severe cancer-related symptoms 4-6 . Systemic therapy, the mainstay of treatment in advanced nsclc, can improve survival by up to 8-12 months in selected patients and can improve symptom control and quality of life in 60%-70% despite treatment toxicity 4,[6][7][8] .Since the year 2000, exciting developments have occurred in the treatment of lung cancer, resulting in a paradigm shift. The approach to lung cancer h...

A Pooled Study on Combination of Gemcitabine and Nedaplatin for Treating Patients with Non-small Cell Lung Cancer

“…And these regimens usually consist of cisplatin or carboplatin with another cytotoxic agent, sometimes in combination with a biologic agent, e.g., bevacizumab. In this setting, the second-line or thirdline treatments recommended for patients with NSCLC could be a platinum with docetaxel, erlotinib, pemetrexed or gemcitabine (Shepherd et al, 2000;Hanna et al, 2004;Shepherd et al, 2005;Leighl et al, 2012 has emerged as an ideal partner for platinum compounds, and its theoretical ability of interfering with the inhibition of repair of platinum-induced DNA damage. Based on the results of several phase III trials, ( Crino et al, 1999;Cardenal et al, 1999;Sandler et al, 2000;Schiller et al, 2002;Scagliotti et al, 2002) gemcitabine in combination with a platinum now represents a commonly used first-line treatment for patients with advanced NSCLC.…”

Surfactant-based drug delivery systems for treating drug-resistant lung cancer

“…Antitumor activity has formerly been showed in numerous studies. In recent studies, novel drugs are examined that develop chemotherapy and target on identifying prospective aspects for beneficial management of cancer (Leighl, 2012). Further research on these pathways may progress our information of the anticancer efficiency and durability, which will confidently progress in management of lung cancer.…”

Bronchoscopic staging of lung cancer

“…Other targeted therapies such as crizotinib in tumors harboring the EML4-ALK gene rearrangement have also recently been highlighted [Leighl, 2012]. Most patients with metastatic NSCLC have inoperable disease and therefore surgical samples from the primary tumor or metastatic lymph nodes are not available for molecular analysis.…”