title: Rescue chemotherapy using multidrug chronomodulated hepatic arterial infusion for patients with heavily pretreated metastatic colorectal cancer.
abstract: BACKGROUND
  : Hepatic arterial infusion (HAI) chemotherapy delivers a high concentration of drugs both to liver metastases and to healthy liver with specific, limiting, hepatobiliary toxicities. Relevant detoxification and cellular proliferation pathways are controlled by the molecular circadian clock in normal liver but not in advanced tumors. In this article, the authors report their experience with chronomodulated HAI chemotherapy as rescue therapy in heavily pretreated patients who had metastatic colorectal cancer.
  
  
  METHODS
  : Data from all consecutive patients with colorectal cancer liver metastases who received HAI with chronomodulated, multidrug chemotherapy regimens in the authors' center after failure on standard chemotherapy were reviewed for efficacy and safety.
  
  
  RESULTS
  : Twenty-nine patients were treated, including 76% with liver metastasis only and 24% with liver and lung metastases. Seventy-five percent of patients had received > or =3 chemotherapy lines, including intravenous, chronomodulated chemotherapy in 59% of patients. Patients received a median of 4 HAI courses (range, 1-9 courses). The most frequent grade (according to National Cancer Institute of Canada Common Toxicity Criteria [version 3]) 3 and 4 nonhematologic toxicities were vomiting, diarrhea, abdominal pain, and fatigue. No severe hematologic or hepatic toxicities and no chemical cholangitis were reported. An objective tumor response was observed in 10 patients (34.5%), including 4 patients who subsequently underwent R0 or R1 hepatic resection. The median progression-free survival and overall survival were 4.5 months (95% confidence limits, 2.4-6.5 months) and 18 months (95% confidence limits, 5.8-30.2 months), respectively.
  
  
  CONCLUSIONS
  : HAI chronomodulated chemotherapy had well tolerated activity in selected, heavily pretreated patients, and the authors believe it deserves to be assessed prospectively in clinical trials among patients who have less advanced disease. Cancer 2009. (c) 2009 American Cancer Society.
authors.affiliation: Chronotherapy Unit, Medical Oncology Department, Hepatobiliary Center, Public Assistance Hospital of Paris, Paul Brousse Hospital, Villejuif, France. mohamed.bouchahda@pbr.aphp.fr
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bouchahda
authors.forename: René
authors.initials: R
authors.lastname: Adam
authors.forename: Sylvie
authors.initials: S
authors.lastname: Giacchetti
authors.forename: Denis
authors.initials: D
authors.lastname: Castaing
authors.forename: Catherine
authors.initials: C
authors.lastname: Brezault-Bonnet
authors.forename: Dominique
authors.initials: D
authors.lastname: Hauteville
authors.forename: Pasquale F
authors.initials: PF
authors.lastname: Innominato
authors.forename: Christian
authors.initials: C
authors.lastname: Focan
authors.forename: David
authors.initials: D
authors.lastname: Machover
authors.forename: Francis
authors.initials: F
authors.lastname: Lévi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D010478:Chemotherapy, Cancer, Regional Perfusion; D002940:Circadian Rhythm; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D019233:Retreatment; D012189:Retrospective Studies