title: A dose-escalation study of irinotecan (CPT-11) in combination with cisplatin in patients with advanced non-small cell lung cancer previously treated with a docetaxel-based front line chemotherapy.
abstract: OBJECTIVE
  A phase I study was conducted to determine the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of a CPT-11 plus cisplatin combination as salvage treatment in patients with advanced non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Twenty-two patients with histologically confirmed NSCLC, who had failed taxotere-based front-line chemotherapy, were enrolled. The patients' median age was 61 years, 19 (86%) were male, and 17 (77%) had a performance status (World Health Organization (WHO)) 0-1. CPT-11 was administered as a 60-min i.v. infusion at a fixed dose of 100 mg/m2 on day 1 and at escalating doses on day 8, starting from 100 mg/m2 with increments of 10 mg/m2; cisplatin was administered at a fixed dose of 80 mg/m2 on day 8, 2 h after CPT-11 administration. Treatment was repeated every 3 weeks.
  
  
  RESULTS
  At the dose of CPT-11 120 mg/m2, three out of four enrolled patients presented DLTs (grade 4 neutropenia, febrile neutropenia and delayed diarrhea); the addition of G-CSF at this level did not permit further dose-escalation. Grade 3/4 neutropenia was observed in 12 (18%) cycles, febrile neutropenia in four (6%), and grade 3/4 thrombocytopenia in four (6%). Grade 3/4 diarrhea was seen in six (29%) patients, and grade 2/3 nausea and vomiting in 12 (57%). Neurotoxicity grade 2 was observed in six (29%) patients and grade 3 in one (5%). Other toxicities were mild. The MTD was CPT-11 100 mg/m2 on day 1 and 110 mg/m2 on day 8 in combination with CDDP 80 mg/m2 on day 8. Among 12 patients evaluable for response, partial response was achieved in two (16.7%) patients and stable disease in five (41.7%).
  
  
  CONCLUSIONS
  The combination of CPT-11 and cisplatin has substantial but manageable toxicity and marginal activity as salvage treatment of patients with NSCLC who have failed taxotere-based front-line chemotherapy: further investigation is warranted to define its precise role in the second-line setting.
authors.affiliation: Department of Medical Oncology, School of Medicine, University General Hospital of Heraklion, Greece. georgoul@med.uch.gr
authors.forename: S
authors.initials: S
authors.lastname: Kakolyris
authors.forename: J
authors.initials: J
authors.lastname: Souglakos
authors.forename: S
authors.initials: S
authors.lastname: Agelaki
authors.forename: C H
authors.initials: CH
authors.lastname: Kourousis
authors.forename: D
authors.initials: D
authors.lastname: Mavroudis
authors.forename: E
authors.initials: E
authors.lastname: Sarra
authors.forename: P
authors.initials: P
authors.lastname: Malliotakis
authors.forename: V
authors.initials: V
authors.lastname: Georgoulias
mesh_terms: D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003967:Diarrhea / Q000139:chemically induced; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology; D016879:Salvage Therapy; D043823:Taxoids
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D000077146:Irinotecan; D017239:Paclitaxel; D002945:Cisplatin; D002166:Camptothecin