title: Is fourth-line chemotherapy routine practice in advanced non-small cell lung cancer?
abstract: BACKGROUND
  Despite advances in palliative chemotherapy, patients with advanced non-small cell lung cancer (NSCLC) eventually experience disease progression during or after completion of first-line chemotherapy, which requires salvage therapy. Second- or third-line therapy in selected patients is recommended in the current guidelines. Although fourth-line therapy is often performed in daily practice in some countries, there are few reports about the clinical benefits of fourth-line therapy.
  
  
  METHODS
  A retrospective review was conducted on 383 patients who underwent at least first-line palliative chemotherapy for advanced NSCLC (stage IV or stage IIIB/recurrent disease unsuitable for definitive local therapy). Overall survival (OS) and clinicopathological characteristics were analyzed according to the lines of chemotherapy as well as for all study patients.
  
  
  RESULTS
  The median OS for all patients after the initiation of first-line therapy was 11 months. The median OS for patients who received fourth- or further-line therapy (77 patients) was longer than that of patients who received third- or lesser-line therapy (27 versus 9 months, p<0.0001). In multivariate analysis, fourth- or further-line therapy was independently associated with favorable OS (hazard ratio: 0.44, 95% confidence interval: 0.34-0.57, p<0.0001) along with recurrent disease, female, age <70 years, and ECOG performance status (PS) 0 or 1. Median OS after the start of fourth-line therapy was 9 months. Good PS (ECOG PS 0, 1) at the initiation of fourth-line therapy (10 versus 2 months, p<0.0001) and disease control (10 versus 7 months, p=0.011) after first-line therapy were associated with favorable OS in univariate analysis, while poor PS (ECOG PS ≥2) was an independent prognostic factor for poor outcome (p<0.0001).
  
  
  CONCLUSIONS
  The present study suggests that advanced NSCLC patients with good PS after progression from third-line therapy could be considered as reasonable candidates for fourth-line therapy in clinical practice.
authors.affiliation: Department of Hematology-Oncology, Ajou University School of Medicine 164 Worldcup-ro, Yeongtong-gu, Suwon, 443-380, Republic of Korea.
authors.forename: Yong Won
authors.initials: YW
authors.lastname: Choi
authors.affiliation: Department of Hematology-Oncology, Ajou University School of Medicine 164 Worldcup-ro, Yeongtong-gu, Suwon, 443-380, Republic of Korea.
authors.forename: Mi Sun
authors.initials: MS
authors.lastname: Ahn
authors.affiliation: Department of Hematology-Oncology, Ajou University School of Medicine 164 Worldcup-ro, Yeongtong-gu, Suwon, 443-380, Republic of Korea.
authors.forename: Geum Sook
authors.initials: GS
authors.lastname: Jeong
authors.affiliation: Department of Hematology-Oncology, Ajou University School of Medicine 164 Worldcup-ro, Yeongtong-gu, Suwon, 443-380, Republic of Korea. Electronic address: hwlee71@gmail.com.
authors.forename: Hyun Woo
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Hematology-Oncology, Ajou University School of Medicine 164 Worldcup-ro, Yeongtong-gu, Suwon, 443-380, Republic of Korea.
authors.forename: Seong Hyun
authors.initials: SH
authors.lastname: Jeong
authors.affiliation: Department of Hematology-Oncology, Ajou University School of Medicine 164 Worldcup-ro, Yeongtong-gu, Suwon, 443-380, Republic of Korea.
authors.forename: Seok Yun
authors.initials: SY
authors.lastname: Kang
authors.affiliation: Department of Hematology-Oncology, Ajou University School of Medicine 164 Worldcup-ro, Yeongtong-gu, Suwon, 443-380, Republic of Korea.
authors.forename: Joon Seong
authors.initials: JS
authors.lastname: Park
authors.affiliation: Department of Hematology-Oncology, Ajou University School of Medicine 164 Worldcup-ro, Yeongtong-gu, Suwon, 443-380, Republic of Korea. Electronic address: jhchoimd@ajou.ac.kr.
authors.forename: Jin-Hyuk
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Preventive Medicine & Public Health, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Soon Young
authors.initials: SY
authors.lastname: Lee
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D019233:Retreatment; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
keywords: Advanced; Fourth-line chemotherapy; Multivariate analysis; Non-small cell lung cancer; Overall survival; Univariate analysis