title: Fever-range whole-body thermal therapy combined with cisplatin, gemcitabine, and daily interferon-alpha: a description of a phase I-II protocol.
abstract: OBJECTIVE
  The purpose of the Phase I component of this study was to find the maximally tolerated dose (MTD) of cisplatin administered within a regimen of fever-range whole body thermal therapy (FR-WB-TT), cisplatin, gemcitabine, and low-dose interferon-alpha (IFN-alpha). The Phase II component aimed to assess which cancer diagnoses responded to the regimen, the response rate, and response duration.
  
  
  METHODS
  The protocol design derived from a schedule-optimized preclinical regimen. Drugs were administered together, and also with thermal therapy in a schedule that optimized the therapeutic index. Eligible patients were those with therapy-resistant, metastatic or advanced solid malignancies. Beginning at 40 mg/m(2), the cisplatin dose was escalated by 10 mg/m(2) to the maximally tolerated dose (MTD) in successive cohorts of 3 patients. A treatment cycle consisted of cisplatin on day one, followed by thermal therapy and simultaneous gemcitabine 36 hours later; then a second dose of gemcitabine one week later; and daily IFN- alpha.
  
  
  RESULTS
  Thirty-seven patients were treated on protocol. The MTD of cisplatin in the thermochemotherapy regimen was established to be 60 mg/m(2). The dose limiting toxicities (DLT) were peripheral neuropathy and ototoxicity. Complete and partial responses combined were 43%. The therapy improved the quality of life of responding patients.
  
  
  CONCLUSIONS
  The protocol was well tolerated and was associated with antitumor activity in patients with a variety of advanced metastatic solid tumors. Tumor response occurred with the thermochemotherapy treatment despite treating malignancies that had progressed on the same chemotherapy drugs administered as standard treatment. Notably, good responses were observed in patients with high-grade neuroendocrine and pancreas cancers. This regimen will be tested in a phase II study.
authors.affiliation: The Division of Oncology, The University of Texas Medical School at Houston, Houston, TX 77030, USA. joan.m.bull@uth.tmc.edu
authors.forename: Joan M C
authors.initials: JM
authors.lastname: Bull
authors.forename: Glenna L
authors.initials: GL
authors.lastname: Scott
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Strebel
authors.forename: Verne L
authors.initials: VL
authors.lastname: Nagle
authors.forename: Dwight
authors.initials: D
authors.lastname: Oliver
authors.forename: Michael
authors.initials: M
authors.lastname: Redwine
authors.forename: R Wanda
authors.initials: RW
authors.lastname: Rowe
authors.forename: Chul W
authors.initials: CW
authors.lastname: Ahn
authors.forename: Steven M
authors.initials: SM
authors.lastname: Koch
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D002945:Cisplatin / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018450:Disease Progression; D004334:Drug Administration Schedule; D000093542:Gemcitabine; D006979:Hyperthermia, Induced; D016898:Interferon-alpha / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D020714:Maximum Tolerated Dose; D009369:Neoplasms / Q000628:therapy; D011788:Quality of Life; D012107:Research Design
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D002945:Cisplatin; D003841:Deoxycytidine; D000093542:Gemcitabine; D016898:Interferon-alpha