title: Phase-II study of dose attenuated schedule of irinotecan, capecitabine, and celecoxib in advanced colorectal cancer.
abstract: BACKGROUND
  The cyclooxygenase-2 (COX-2) enzyme plays a major role in tumor progression and resistance to chemotherapy. A Phase-II study was undertaken to determine the activity of a dose attenuated schedule of irinotecan, capecitabine, and the COX-2 inhibitor celecoxib in patients with advanced colorectal cancer.
  
  
  METHODS
  The eligibility criteria included a pathologically or cytologically confirmed diagnosis of adenocarcinoma of the colon or rectum that was metastatic. Patients received a combination of irinotecan 70 mg/m2 over 30 min I.V. on days 1 and 8, capecitabine 1,000 mg/m2 twice per day orally on days 1-14, and celecoxib at a daily dose of 800 mg continuously. Cycles were repeated every 21 days.
  
  
  RESULTS
  Fifty-one patients were enrolled (median age 58 years; M : F 31 : 20). The objective response rate was 21/51 = 41% [95% confidence intervals (CI), 0.28-0.55]. The median time to progression was 7.7 months (95% CI, 6.2-8.6 months). Median survival time and probability of survival at 1 year were 21.2 months (95% CI, 13.8-n/a), and 75% (95% CI, 0.63-0.88), respectively. The major toxicity was Grade 3 or 4 diarrhea, seen in 24 and 10% of patients, respectively. There were no treatment related deaths.
  
  
  CONCLUSIONS
  The lower dose intensity of irinotecan appeared to maintain activity and improve tolerability when combined with capecitabine. The addition of celecoxib to irinotecan and capecitabine did not appear to significantly increase the activity of this doublet based on the RECIST criteria for objective response.
authors: Karmanos Cancer Institute, Wayne State University, 4100 John R Street, Detroit, MI 48201, USA. elrayesb@karmanos.org
authors: Bassel F
authors: BF
authors: El-Rayes
authors: Mark M
authors: MM
authors: Zalupski
authors: Stephanie G
authors: SG
authors: Manza
authors: Barbara
authors: B
authors: Rusin
authors: Ann Marie
authors: AM
authors: Ferris
authors: Ulka
authors: U
authors: Vaishampayan
authors: Lance K
authors: LK
authors: Heilbrun
authors: Raghu
authors: R
authors: Venkatramanamoorthy
authors: Anthony F
authors: AF
authors: Shields
authors: Philip A
authors: PA
authors: Philip
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine; D000068579:Celecoxib; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage; D016019:Survival Analysis; D017211:Treatment Failure
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D000068579:Celecoxib; D005472:Fluorouracil; D002166:Camptothecin