title: Outcomes of Platinum-Sensitive Small-Cell Lung Cancer Patients Treated With Platinum/Etoposide Rechallenge: A Multi-Institutional Retrospective Analysis.
abstract: Small-cell lung cancer has a high chemotherapeutic sensitivity but with disappointing outcome results. Patients with “sensitive disease” are those who respond to treatment with a long relapse-free interval (RFI): in these cases rechallenge with first-line chemotherapy might represent a therapeutic opportunity. Our largest retrospective experience confirmed that rechallenge is feasible with interesting outcome results; there are no statistical differences between RFI and outcome.
  
  
  BACKGROUND
  Patients with small-cell lung cancer (SCLC) that progresses after first-line (FL) chemotherapy have a poor prognosis and second-line (SL) chemotherapy has limited efficacy. Patients whose disease relapses/progresses > 90 days after FL platinum-based treatment are considered platinum-sensitive and could be rechallenged with a similar regimen. We conducted a multicenter retrospective analysis to evaluate outcomes of SCLC patients rechallenged with platinum/etoposide.
  
  
  METHODS
  Records of all SCLC patients treated in 7 institutions between January 2007 and December 2011 were reviewed. The primary end point was overall survival from the time of rechallenge (OS-R); secondary end points were progression-free survival (PFS) and overall survival from the time of diagnosis (OS-D). Survival curves were calculated using the Kaplan-Meier method.
  
  
  RESULTS
  Of the 2000 SCLC patients identified, 112 (5.6%) had sensitive disease treated with rechallenge platinum/etoposide; 65% were men with a median age of 64 years. At the time of diagnosis, 44% of patients had limited disease, 82% had an Eastern Cooperative Oncology Group performance status of 0 to 1. A median of 4 cycles of rechallenge was administered. Tumor response was 3% for complete response and 42% for partial response, 19% of patients maintained stable disease, 27% progressive disease, and 9% were not evaluable. Median PFS from the time of rechallenge was 5.5 months (95% confidence interval [CI], 4.4-6.3). Median OS-R and OS-D were 7.9 months (95% CI, 6.9-9.7) and 21.4 months (95% CI, 19.8-24.1), respectively. Subgroup analysis according to relapse-free interval (90-119 vs. 120-149 vs. > 150 days) did not show any statistically significant difference in PFS or OS-R.
  
  
  CONCLUSIONS
  The outcome for SL chemotherapy for SCLC is poor. Rechallenge platinum/etoposide is a reasonable option with potentially better outcomes than standard chemotherapy.
authors.affiliation: Department of Medical Oncology, AUSL Bologna, Italy. Electronic address: g.genestreti@ausl.bologna.it.
authors.forename: Giovenzio
authors.initials: G
authors.lastname: Genestreti
authors.affiliation: Department of Medical Oncology, University Hospital of Parma, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Tiseo
authors.affiliation: Division of Thoracic Oncology, Shizouka Cancer Center, Shizouka, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Kenmotsu
authors.affiliation: Division of Thoracic Oncology, Shizouka Cancer Center, Shizouka, Japan.
authors.forename: Wakuda
authors.initials: W
authors.lastname: Kazushige
authors.affiliation: Department of Medical Oncology, AUSL Bologna, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Di Battista
authors.affiliation: Department of Medical Oncology, AUSL Bologna, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cavallo
authors.affiliation: Department of Medical Oncology, AUSL Rimini, "Cervesi" Hospital, Cattolica, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Carloni
authors.affiliation: Department of Medical Oncology, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Meldola, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bongiovanni
authors.affiliation: Department of Medical Oncology, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Meldola, Italy.
authors.forename: Marco Angelo
authors.initials: MA
authors.lastname: Burgio
authors.affiliation: Department of Medical Oncology, "Santa Maria delle Croci" Hospital, Ravenna, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Casanova
authors.affiliation: Department of Medical Oncology, "S. Maria della Misericordia" Hospital, Perugia, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Metro
authors.affiliation: Unit of Biostatistics and Clinical Trials, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Meldola, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Scarpi
authors.affiliation: Dr Luffi Kirdar Research and Training Hospital, Istanbul, Turkey.
authors.forename: Taner
authors.initials: T
authors.lastname: Korkmaz
authors.affiliation: Marmara University Hospital, Department of Medical Oncology, Istambul, Turkey.
authors.forename: Seber
authors.initials: S
authors.lastname: Selcuk
authors.affiliation: Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: Kurup
authors.initials: K
authors.lastname: Roopa
authors.affiliation: Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Califano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D017671:Platinum Compounds / Q000627:therapeutic use*; D012189:Retrospective Studies; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D017671:Platinum Compounds; D005047:Etoposide; D019772:Topotecan; D002945:Cisplatin
keywords: Extended disease; Platinum sensitive; Rechallenge chemotherapy; SCLC; Second-line