title: Phase II trial of fortnightly irinotecan (CPT-11) in the treatment of colorectal cancer patients resistant to previous fluoropyrimidine-based chemotherapy.
abstract: BACKGROUND
  This phase II study investigated the anti-tumour activity and toxicity of CPT-11 (250 mg/m2 i.v. infusion over 60 minutes) administered every 2 weeks as second-line chemotherapy in patients with advanced colorectal cancer (CRC).
  
  
  METHODS
  Patients (n = 63) with histology diagnosis of advanced CRC and proven resistance to previous fluoropyrimidine therapy were enrolled.
  
  
  RESULTS
  A total of 510 CPT-11 cycles were administered, with a mean of 8 cycles per patient (range: 1-32). The median relative dose intensity was 93%. Partial response (PR) was obtained in 11 patients (17.5%; 95%CI: 8.1%-26.7%) and 29 patients (46.0%) showed stable disease (clinical benefit of 63.5%). The median duration of response was 6.8 months (95%CI: 6.1-7.5 months), median survival was 8.8 months (95%CI: 6.3-11.5 months) and median time to disease progression was 4.5 months (95%CI: 3.9-5.0 months). Overall, this schedule of CPT-11 chemotherapy was well tolerated by the patient. Neutropenia was the most frequent grade 3/4 haematological toxicity (20.6% of patients and 4.1% of cycles). Neutropenia with concurrent fever or infection occurred in 7 patients (11.1%). Late onset diarrhoea was the most frequent grade 3/4 non-haematological toxicity (19.0% of patients and 2.3% of cycles). Other, lower-incidence, toxicities were anaemia, fever, infection, mucositis, nausea and vomiting. There were no toxic deaths.
  
  
  CONCLUSIONS
  We found that CPT-11, administered as 250 mg/m2 i.v. infusion over 60 minutes every 2 weeks, was active and well tolerated schedule in the second-line chemotherapy of advanced CRC patients. This bi-weekly scheme could be used as an alternative to the weekly or the every-three-week schedule as well as in combined therapies with other chemotherapeutic agents for the treatment of advanced, metastatic, CRC.
authors.affiliation: Servicio de Oncologia Medica, Hospital General Yagüe, Burgos, Spain. giron@bio.hgy.es
authors.forename: Carlos
authors.initials: C
authors.lastname: García-Girón
authors.forename: Andrés
authors.initials: A
authors.lastname: García Palomo
authors.forename: Carmen
authors.initials: C
authors.lastname: Alonso López
authors.forename: Angel
authors.initials: A
authors.lastname: León Carbonero
authors.forename: Miguel
authors.initials: M
authors.lastname: Méndez Ureña
authors.forename: Encarna
authors.initials: E
authors.lastname: Adróver Cebrián
authors.forename: Ramón
authors.initials: R
authors.lastname: Barceló Galíndez
authors.forename: Mónica
authors.initials: M
authors.lastname: Arroyo Yustos
authors.forename: José
authors.initials: J
authors.lastname: Alvarez Gallego
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil; D006801:Humans; D000077146:Irinotecan; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016019:Survival Analysis
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin