title: Three-week versus four-week schedule of cisplatin and gemcitabine: results of a randomized phase II study.
abstract: BACKGROUND
  The cisplatin and gemcitabine (GC) regimen is usually administered as a 4- or 3-week schedule; however, the best schedule to use is still unclear. We therefore started a randomized phase II trial to compare toxicity and dose intensity (DI) between these two GC schedules.
  
  
  METHODS
  Ninety-six patients with non-small-cell lung cancer (NSCLC) and an additional 11 patients with an advanced epithelial neoplasm [bladder (n = 5), head and neck (n = 3), cervix (n = 1), esophageal (n = 1) or unknown primary carcinoma (n = 1)] were randomized to receive cisplatin 70 mg/m(2) intravenously on day 2 plus either gemcitabine 1000 mg/m(2) on days 1, 8 and 15 of a 28-day cycle or gemcitabine 1000 mg/m(2) on days 1 and 8 of a 21-day cycle. Planned DI (PDI) for the 4-week schedule was 750 mg/m(2)/week for gemcitabine and 17.5 mg/m(2)/week for cisplatin; for the 3-week regimen PDI was 666 mg/m(2)/week and 23 mg/m(2)/week for gemcitabine and cisplatin, respectively.
  
  
  RESULTS
  From July 1998 to March 2000, 107 patients were randomized. Grade 3/4 neutropenia was observed in 27.8% of patients in the 3-week versus 22.5% in the 4-week arm (P = 0.69), while grade 3/4 thrombocytopenia was higher in the 4-week arm (29.5% versus 5.5% of patients; P = 0.14). A total of 398 cycles of therapy were delivered. Overall, 51% of cycles were modified in dose, timing or both in the 4-week arm, and 19% in the 3-week arm. The 21-day schedule of GC leads to a similar received DI of gemcitabine and higher cisplatin DI. Both regimens had activity in NSCLC, with a response rate of 39% (38% for the 4-week arm, and 42% for the 3-week arm).
  
  
  CONCLUSIONS
  The 3-week schedule has similar DI to the 4-week schedule. However the 3-week regimen has a better compliance profile and a comparable response rate in NSCLC, supporting the use of such a schedule.
authors.affiliation: Department of Medical Oncology and Hematology and Division of Thoracic Surgery, Istituto Clinico Humanitas, Rozzano-Milan, Italy. hector.sotoparra@humanitas.it
authors.forename: H
authors.initials: H
authors.lastname: Soto Parra
authors.forename: R
authors.initials: R
authors.lastname: Cavina
authors.forename: F
authors.initials: F
authors.lastname: Latteri
authors.forename: A
authors.initials: A
authors.lastname: Sala
authors.forename: M
authors.initials: M
authors.lastname: Dambrosio
authors.forename: G
authors.initials: G
authors.lastname: Antonelli
authors.forename: E
authors.initials: E
authors.lastname: Morenghi
authors.forename: M
authors.initials: M
authors.lastname: Alloisio
authors.forename: G
authors.initials: G
authors.lastname: Ravasi
authors.forename: A
authors.initials: A
authors.lastname: Santoro
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D016001:Confidence Intervals; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D012016:Reference Values; D016019:Survival Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine