title: Gemcitabine and cisplatin combined with regional hyperthermia as second-line treatment in patients with gemcitabine-refractory advanced pancreatic cancer.
abstract: OBJECTIVE
  There is no standard second-line therapy for patients with advanced pancreatic cancer (APC) after gemcitabine (G) failure. Cisplatin (Cis)-based chemotherapy has shown activity in APC. It is proven that cytotoxicity of G and Cis is enhanced by heat exposure at 40° to 42°C. Therefore G plus Cis with regional hyperthermia (RHT) might be beneficial for patients with G-refractory APC.
  
  
  METHODS
  We retrospectively analysed 23 patients with advanced (n = 2) or metastatic (n = 21) pancreatic cancer with relapse after G mono first-line chemotherapy (n = 23). Patients had received G (day 1, 1000 mg/m(2)) and Cis (day 2 and 4, 25 mg/m(2)) in combination with RHT (day 2 and 4, 1 h) biweekly for 4 months. We analysed feasibility, toxicity, time to second progression (TTP2), overall survival (OS) and clinical response.
  
  
  RESULTS
  Between October 1999 and August 2008 23 patients were treated. Haematological toxicity was low with no grade 4 event. Hyperthermia-associated toxicity consisted of discomfort because of bolus pressure (3%), power-related pain (7%) or position-related pain (17%). Median TTP1 was 5.9 months (95% confidence interval (CI): 2.6-9.2), median TTP2 was 4.3 months (95%CI: 1.2-7.4) and OS 12.9 months (95%CI: 9.9-15.9). The disease control rate in 16 patients with available CT scans was 50%.
  
  
  CONCLUSIONS
  We show first clinical data of G plus Cis with RHT being clinically active in G-pretreated APC with low toxicity. A prospective controlled phase II second-line clinical trial (EudraCT: 2005-003855-11) and a randomised phase III adjuvant clinical trial offering this treatment (HEAT; EudraCT: 2008-004802-14) are currently open for recruitment.
authors.affiliation: Department of Internal Medicine III, Klinikum Grosshadern Medical Centre, Ludwig-Maximilians-University, Munich, Germany. Katharina.Lechner@med.uni-muenchen.de
authors.forename: Katharina Elisabeth
authors.initials: KE
authors.lastname: Tschoep-Lechner
authors.forename: Valeria
authors.initials: V
authors.lastname: Milani
authors.forename: Frank
authors.initials: F
authors.lastname: Berger
authors.forename: Nelli
authors.initials: N
authors.lastname: Dieterle
authors.forename: Sultan
authors.initials: S
authors.lastname: Abdel-Rahman
authors.forename: Christoph
authors.initials: C
authors.lastname: Salat
authors.forename: Rolf-Dieter
authors.initials: RD
authors.lastname: Issels
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D021441:Carcinoma, Pancreatic Ductal / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000628:therapy*; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine