title: Hepatic arterial infusion with irinotecan in patients with liver metastases of colorectal cancer: results of an extended phase I study.
abstract: BACKGROUND
  To define the maximum tolerated dose (MTD) tolerability and efficacy of intra-arterial chemotherapy with irinotecan in patients with liver metastases of colorectal carcinoma (CRC).
  
  
  METHODS
  Superselective intra-arterial irinotecan was applied on days 1, 14, 28 and 42. The initial dose was 140 mg/m² with escalation in the subsequent patient group to 160 mg/m². The final protocol toxicity evaluation was 260 mg/m². Patients required histologically proven disease and adequate bone marrow, liver and renal function, no extrahepatic metastasis and a life expectancy >12 weeks. results: Thirty-three patients were enrolled (median age 65, range 49-78 years). On dose level VI (240 mg/m²), 1 case of dose-limiting toxicity (DLT) (granulocytopenia) was observed, leading to an enlarged cohort of 6 patients. As no additional DLT was detected on this level, an escalation to level VII was performed. On the dose level of 260 mg/m², irinotecan DLTs were observed, resulting in the termination of escalation and the declaration of dose level VI as MTD. Imaging follow-up with Response Evaluation Criteria in Solid Tumors (RECIST) criteria revealed a complete response in 1 patient, stable disease in 31 patients, and progressed disease in 1 patient. The median time to progression was 4.7 months, the median overall survival 15.6 months.
  
  
  CONCLUSIONS
  The method of intra-arterial chemotherapy with irinotecan is well tolerated and shows promising local response rates in liver metastases of CRC.
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Johann Wolfgang Goethe University, Frankfurt am Main, Germany. k.eichler@em.uni-frankfurt.de
authors.forename: K
authors.initials: K
authors.lastname: Eichler
authors.forename: T
authors.initials: T
authors.lastname: Dufas
authors.forename: R
authors.initials: R
authors.lastname: Hammerstingl
authors.forename: T
authors.initials: T
authors.lastname: Gruber-Rouh
authors.forename: T J
authors.initials: TJ
authors.lastname: Vogl
authors.forename: S
authors.initials: S
authors.lastname: Zangos
mesh_terms: D000368:Aged; D000380:Agranulocytosis / Q000209:etiology; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007269:Injections, Intra-Arterial; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D014057:Tomography, X-Ray Computed
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin