Preclinical and Clinical Aspects of Carboplatin and Gemcitabine Combined with Whole-body Hyperthermia for Pancreatic Adenocarcinoma

AFSANEH BAKSHANDEH-BATH1, ANNE S. STOLTZ1, NILS HOMANN2, THOMAS WAGNER1, STEPHANIE ST.LTING1* and STEFAN O. PETERS1*

Divisions of 1Hematology and 2Gastroenterology, Medical Department I, Medical University of Schleswig-Holstein-Luebeck, Luebeck, Germany

Abstract. Advanced pancreatic adenocarcinoma is usually treated with single-agent gemcitabine chemotherapy or combinations that include gemcitabine application that have palliative benefit but do not lead to survival benefits. We present the results of preclinical and clinical studies using combination chemotherapies that include 41.8˚C whole-body hyperthermia for pancreatic adenocarcinoma. Materials and Methods: DAN-G pancreatic carcinoma cells were treated with carboplatin and gemcitabine in vitro under hyperthermic conditions of 37˚C, 39˚C, 41.8˚C and 43˚C and cytotoxic drug effects were measured under various conditions using crystal violet assays. Data on outcome and toxicity of a clinical study using gemcitabine and carboplatin with 41.8˚C whole-body hyperthermia in a compassionate manner in patients with advanced and heavily pretreated pancreatic adenocarcinoma are also shown. Results: In vitro data showed the DAN-G cells did not show increased responses to gemcitabine with or without carboplatinum under hyperthermic culture conditions at 39 and 41.8˚C. Only temperatures of 43˚C led to increased hyperthermic
damage. Clinical data showed that a therapy of whole-body hyperthermia at 41.8˚C with gemcitabine and carboplatin was well tolerated leading mainly to the expected hematological side-effects due to chemotherapy. The median overall survival after whole-body-hyperthemia was of 357 days, with a median progression-free survival of 140 days.

Conclusion: Preclinical data indicate that hyperthermia does not increase the chemosensitivity of DAN-G pancreatic carcinoma cells to gemcitabine and carboplatin. Clinical data show that a treatment of pancreatic adenocarcinoma with C whole-body hyperthermia at 41.8˚ with gemcitabine and carboplatin is feasible for patients with advanced disease.

 

WBH Pancreatic Ca 2009
WBH Pancreatic Ca 2009
WBH Pancreatic Ca 2009.pdf
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