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Background Small cell lung cancer (SCLC) is an aggressive disease and chemotherapy (CT) is the mainstay of treatment. Despite good response rates most patients (pts) will relapse and die of this disease. Standard 1st-line CT in limited (LD) and extensive stage disease is usually etoposide with platinum (P) or CAV (cyclophosphamide, doxorubicin, vincristine). At progression, 2nd-line CT may involve re-challenging with the 1st-line regimen. For pts who progress after 2 lines of CT, there is little evidence to guide treatment decisions, and the benefit of 3rd-line CT is unclear. Objective To determine the clinical benefit of 3rd-line CT for SCLC. Study design An international multi-centre retrospective analysis of pts who received 3 lines of CT for SCLC from 2001-2011 was performed. Baseline demographics, known prognostic factors and CT details were recorded. The main end-points were response rate (RR) and overall survival (OS) after 3rd-line CT. Results A total of 124 eligible pts were identified; 59% male, median age 61, 89% ECOG 0-1, 40% LD. First-line P-based CT was given to 99% of pts, with a RR of 90%. In the 2nd-line, 70 pts (56%) were re-challenged with similar CT, with the remaining receiving either CAV or topotecan based CT, with an RR of 50%. In the 3rd-line, 35 pts (28%) were re-challenged with CT similar to a prior regimen. Only 27 pts (22%) received 3 distinct lines of CT. Median progression free survival (PFS) in the 1st, 2nd and 3rd-lines were: 9.0, 4.6 and 2.0 months respectively. The RR in the 3rd-line was 17%, with no complete responses. Median 3rd-line OS was 4.8 months. Factors associated with longer OS were: normal baseline serum LDH (p = 0.02), response to 2nd-line CT (p = 0.04) and PFS >3 months after 2nd-line CT (p = 0.05). Age, sex, initial disease stage, and CT re-challenges did not predict longer survival. After the 3rd-line, 35 pts received further CT. Conclusions In 5 cancer centres, over 10 years, few SCLC pts received 3 lines of CT. Most who received 3 lines had been re-challenged with a similar regimen at least once. OS and RR in the 3rd-line are modest. Lack of response to, or progression after 2nd-line CT may predict particular lack of benefit in the 3rd-line. Prospective research in this area is needed. Disclosure All authors have declared no conflicts of interest. |
