title: Cisplatin-based chronotherapy for advanced non-small cell lung cancer patients: a randomized controlled study and its pharmacokinetics analysis.
abstract: OBJECTIVE
  We intended to evaluate the superiority of cisplatin-based chronotherapy in the treatment of patients with advanced non-small cell lung cancer (NSCLC) and investigate the relationship between the circadian rhythm and the variability of pharmacokinetics for cisplatin.
  
  
  METHODS
  Forty-one patients with advanced NSCLC were divided into two groups with minimization randomization, including routine group (24 cases) and chronotherapy group (17 cases). The clinical effect and toxicity between the two groups were investigated. The population pharmacokinetics of cisplatin was calculated using nonlinear mixed-effects modeling method.
  
  
  RESULTS
  There is no significant difference in total response rate between chronotherapy group (52.94%) and routine chemotherapy group (50.00%), p = 0.853. The rate of leucopenia (grade 3 or 4) in chronotherapy group (11.76%) is significantly lower than that in routine chemotherapy (37.50%), p < 0.05. The rate of neutropenia (grade 3 or 4) in chronotherapy group (11.76%) is significantly lower than that in routine chemotherapy group (33.33%), p < 0.05. The proportion of gastrointestinal toxicity (nausea, grade 1 vs 2) in chronotherapy group is significantly lower than that in routine chemotherapy, p < 0.05. When cisplatin was administered at 18:00, the CL was 1.38- and 1.22-fold higher than those administered at 6:00 for total and unbound cisplatin, respectively (p < 0.05).
  
  
  CONCLUSIONS
  Cisplatin-based chronotherapy has advantage in relieving side effects of chemotherapy, and circadian could influence the metabolism of cisplatin, and more clinical researches are needed.
authors.affiliation: Department of Clinical pharmacy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiang Su, China, Lavendercz@sina.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Rong
authors.initials: R
authors.lastname: Chen
authors.forename: Mei
authors.initials: M
authors.lastname: Ji
authors.forename: Su-Lan
authors.initials: SL
authors.lastname: Zou
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Zhu
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D055870:Drug Chronotherapy; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging
chemical_list: D002945:Cisplatin