Preclinical and clinical aspects of carboplatin and gemcitabine combined with whole-body hyperthermia for pancreatic adenocarcinoma.
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 degrees C whole-body hyperthermia for pancreatic adenocarcinoma.


METHODS
DAN-G pancreatic carcinoma cells were treated with carboplatin and gemcitabine in vitro under hyperthermic conditions of 37 degrees C, 39 degrees C, 41.8 degrees C and 43 degrees 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 degrees 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 degrees C. Only temperatures of 43 degrees C led to increased hyperthermic damage. Clinical data showed that a therapy of whole-body hyperthermia at 41.8 degrees 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.


CONCLUSIONS
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 degrees with gemcitabine and carboplatin is feasible for patients with advanced disease.
Bakshandeh-Bath
Afsaneh
A
Division of Hematology, Medical Department I, Medical University of Schleswig-Holstein-Luebeck, Luebeck, Germany.
Stoltz
Anne S
AS
Homann
Nils
N
Wagner
Thomas
T
Stölting
Stephanie
S
Peters
Stefan O
SO
D000230:Adenocarcinoma / Q000556:secondary / Q000628:therapy*; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002453:Cell Cycle / Q000187:drug effects; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D008113:Liver Neoplasms / Q000556:secondary / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*; D010865:Pilot Projects; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
D003841:Deoxycytidine; D016190:Carboplatin; D000093542:Gemcitabine