title: Duodenal ischemia and upper GI bleeding are dose-limiting toxicities of 24-h continuous intra-arterial pancreatic perfusion of gemcitabine following vascular isolation of the pancreatic head: early results from the Regional Chemotherapy in Locally Advanced Pancreatic Cancer (RECLAP) study.
abstract: BACKGROUND
  Regional chemotherapy is used successfully in the treatment of both primary and secondary malignancies, in particular of the peritoneal surface and the liver, and is currently explored as an attractive approach for patients with locally advanced pancreatic ductal adenocarcinoma. To establish the feasibility and toxicity of regional intra-arterial gemcitabine delivered as a 24-h continuous infusion to the pancreas as a novel treatment option for patients with locally advanced PDAC a phase I clinical trial was conducted.
  
  
  METHODS
  Between April 2011 and September 2013 six patients with biopsy confirmed, borderline or unresectable pancreatic adenocarcinoma, and having received at least one line of systemic chemotherapy, underwent vascular redistribution of the inflow to the head of the pancreas by arterial coil embolization followed by perfusion catheter placement within the splenic artery. Patients were treated with increasing doses of gemcitabine administered by continuous splenic arterial infusion over 24 h with inter-patient and intra-patient dose escalation scheme. The primary endpoint was toxicity of the intra-arterial gemcitabine regimen and to establish the maximum tolerated dose.
  
  
  RESULTS
  Catheter placement and gemcitabine infusion was successful in all patients enrolled to date (n = 6). Four out of six patients experienced catheter tip migration requiring replacement or revision. Patients received a median of four doses of 24-h gemcitabine infusion. Two patients developed grade 3 and 4 duodenal ischemia and upper gastrointestinal bleeding. Median overall survival was 15.3 months and median time to progression was 3 months. Three patients (50 %, n = 3/6) progressed systemically. Two patients had stable disease >4 months following treatment and underwent pancreaticoduodenectomy.
  
  
  CONCLUSIONS
  While technically feasible to treat locally advanced pancreatic ductal adenocarcinoma, prolonged regional pancreatic perfusion with gemcitabine following pancreatic arterial redistribution carries a high risk for gastrointestinal toxicity. Shorter infusion schedules with frequent on treatment evaluations should be considered for future clinical trials.
authors.affiliation: Thoracic & GI Oncology Branch, National Cancer Institute, Hatfield Center, CCR - 4 West/5940 10 Center Drive, Bethesda, MD, 20892-0001, USA.
authors.forename: Joal D
authors.initials: JD
authors.lastname: Beane
authors.forename: Kayla F
authors.initials: KF
authors.lastname: Griffin
authors.forename: Elliot B
authors.initials: EB
authors.lastname: Levy
authors.forename: Prakash
authors.initials: P
authors.lastname: Pandalai
authors.forename: Bradford
authors.initials: B
authors.lastname: Wood
authors.forename: Nadine
authors.initials: N
authors.lastname: Abi-Jaoudeh
authors.forename: Tatiana
authors.initials: T
authors.lastname: Beresnev
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Shutack
authors.forename: Carole C
authors.initials: CC
authors.lastname: Webb
authors.forename: Itzhak
authors.initials: I
authors.lastname: Avital
authors.forename: Udo
authors.initials: U
authors.lastname: Rudloff
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy; D002404:Catheterization; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004378:Duodenal Diseases / Q000139:chemically induced*; D004386:Duodenum / Q000098:blood supply / Q000187:drug effects; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced*; D006801:Humans; D007511:Ischemia / Q000139:chemically induced*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010179:Pancreas / Q000098:blood supply; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D010477:Perfusion; D013157:Splenic Artery; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine