title: Irinotecan and cisplatin with concurrent thoracic radiotherapy in a once-every-three-weeks schedule in patients with limited-disease small-cell lung cancer: a phase I study.
abstract: BACKGROUND
  Irinotecan and cisplatin with concurrent radiotherapy is a powerful treatment combination for patients with limited-disease small-cell lung cancer (LD-SCLC). The objective was to determine the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of irinotecan and cisplatin with concurrent thoracic radiotherapy (TRT) as a once-every-three-weeks schedule.
  
  
  METHODS
  Patients with LD-SCLC received a fixed-dose of irinotecan (340 mg) and cisplatin (135mg) at day 1 in cycles 1 and 4. During cycles 2 and 3, irinotecan and cisplatin were given in a dose-escalation schedule with concurrent TRT (once daily, total dose 45Gray).
  
  
  RESULTS
  No DLT was observed at first two levels (irinotecan 100mg or 120 mg and cisplatin 100mg at day 1 of cycles 2 and 3). In the first five patients, four episodes of grade III diarrhoea/dehydration were observed at cycles 1 and 4. Therefore, from the sixth patient on, fixed-dose irinotecan at cycles 1 and 4 was reduced to 250 mg. At the subsequent level of irinotecan 140 mg and cisplatin 100mg in cycles 2 and 3, two DLTs (severe oesophagitis and late vertebral radiation toxicity) were observed in one patient.
  
  
  CONCLUSIONS
  Irinotecan 140 mg and cisplatin 100mg with concurrent TRT was considered the MTD. Irinotecan and cisplatin in a once-every-three-weeks schedule is not recommended due to severe toxicity. Irinotecan may be more suited for intermittent weekly administration.
authors.affiliation: Department of Pulmonology, University Medical Center Groningen, University of Groningen, The Netherlands. w.k.de.jong@int.umcg.nl
authors.forename: W K
authors.initials: WK
authors.lastname: de Jong
authors.forename: M J A
authors.initials: MJ
authors.lastname: de Jonge
authors.forename: A H D
authors.initials: AH
authors.lastname: van der Leest
authors.forename: J P
authors.initials: JP
authors.lastname: van Meerbeeck
authors.forename: H J M
authors.initials: HJ
authors.lastname: Groen
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011878:Radiotherapy / Q000009:adverse effects
chemical_list: D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin