title: Chronomodulated administration of oxaliplatin plus capecitabine (XELOX) as first line chemotherapy in advanced colorectal cancer patients: phase II study.
abstract: BACKGROUND
  The combination of 5-fluorouracil (5-FU), leucovorin (LV), and oxaliplatin (I-OHP) was shown to be both more active against metastatic colorectal carcinoma and better tolerated if the drug delivery rate was chronomodulated according to circadian rhythms rather than constant. The aim of the present study was to define the feasibility and efficacy of XELOX administered through a new chronomodulated schedule in untreated advanced colorectal cancer (CRC) patients.
  
  
  METHODS
  Chemotherapy-naive patients with advanced CRC were considered eligible for the study accrual.
  
  
  METHODS
  oxaliplatin 70 mg/m(2) continuous infusion (c.i.) for 12 h (8:00 a.m. to 8:00 p.m.) days 1, 8 plus chronomodulated oral capecitabine 1,750 mg/m(2)/die (h 8:00 a.m. 25% of total dose; h 6:00 p.m. 25% of total dose; h 11:00 p.m. 50% of total dose), days 1-14 every 21 days.
  
  
  RESULTS
  Forty-six patients were evaluated for safety and efficacy (male/female, 20/26). Median age was 64 years (range 28-77 years). Median Eastern Cooperative Oncology Group performance status (PS) was 0 (range 0-1). A total of 324 cycles have been administered: median per patient 6 (range 3-10 courses). Median number of metastatic sites was 1. Metastatic sites distribution was as follows: liver (65.2%), lung (34.8%), and nodes (32.6%). Median follow-up was 14 months (range 6.0-40.3 months). In an intent-to-treat efficacy analysis, objective response and stable disease were recorded in 27 (58.6%) and in 16 patients (34.9%), respectively. The median response duration was 8.0 months (95% CI; 5.03-10.96 months). The median time to progression (TTP) was 9.0 months (95% CI; 6.47-11.52 months). The overall survival (OS) was not reached, with a median value > 24 months (95% CI; 23.66-36.30 months). The grade 3 toxicities were diarrhea (8.7%), liver toxicity (13.1%), fatigue (8.7%), neurotoxicity (2.2%), neutropenia (8.7%), and thrombocytopenia (2.2%).
  
  
  CONCLUSIONS
  This regimen resulted of particular interest for patients with untreated metastatic CRC.
authors.affiliation: Medical Oncology, University Campus Bio-Medico, Via Emilio Longoni, 69, 00155 Rome, Italy. d.santini@unicampus.it
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.forename: Gaia
authors.initials: G
authors.lastname: Schiavon
authors.forename: Marisa
authors.initials: M
authors.lastname: Di Seri
authors.forename: Vladimir
authors.initials: V
authors.lastname: Virzí
authors.forename: Bruno
authors.initials: B
authors.lastname: Spalletta
authors.forename: Marco
authors.initials: M
authors.lastname: Caricato
authors.forename: Roberto
authors.initials: R
authors.lastname: Coppola
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077150:Oxaliplatin; D010071:Oxaloacetates; D011355:Prodrugs / Q000008:administration & dosage; D018401:Sample Size; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D004338:Drug Combinations; D009944:Organoplatinum Compounds; D010071:Oxaloacetates; D011355:Prodrugs; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil