Fever-range whole-body thermal therapy combined with cisplatin, gemcitabine, and daily interferon-α: A description of a phase I-II protocol

Joan M C Bull, Glenna L. Scott, Frederick R. Strebel, Verne L. Nagle, Dwight Oliver, Michael Redwine, R. Wanda Rowe, Chul W. Ahn, Steven M. Koch

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Purpose: 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-α). The Phase II component aimed to assess which cancer diagnoses responded to the regimen, the response rate, and response duration. Materials and 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/m2, the cisplatin dose was escalated by 10 mg/m2 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-α. Results: Thirty-seven patients were treated on protocol. The MTD of cisplatin in the thermochemotherapy regimen was established to be 60 mg/m2. 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)649-662
Number of pages14
JournalInternational Journal of Hyperthermia
Volume24
Issue number8
DOIs
StatePublished - 2008

Fingerprint

gemcitabine
Interferons
Cisplatin
Fever
Hot Temperature
Maximum Tolerated Dose
Therapeutics
Neoplasms
Interferon-alpha
Appointments and Schedules
Peripheral Nervous System Diseases
Pancreatic Neoplasms
Pharmaceutical Preparations

Keywords

  • Cisplatin
  • Fever-range whole-body thermal therapy (FR-WB-TT)
  • Gemcitabine
  • Interferon-α (IFN-α)
  • Optimized timing/schedule

ASJC Scopus subject areas

  • Cancer Research
  • Physiology
  • Radiological and Ultrasound Technology
  • Physiology (medical)

Cite this

Fever-range whole-body thermal therapy combined with cisplatin, gemcitabine, and daily interferon-α : A description of a phase I-II protocol. / Bull, Joan M C; Scott, Glenna L.; Strebel, Frederick R.; Nagle, Verne L.; Oliver, Dwight; Redwine, Michael; Rowe, R. Wanda; Ahn, Chul W.; Koch, Steven M.

In: International Journal of Hyperthermia, Vol. 24, No. 8, 2008, p. 649-662.

Research output: Contribution to journalArticle

Bull, Joan M C ; Scott, Glenna L. ; Strebel, Frederick R. ; Nagle, Verne L. ; Oliver, Dwight ; Redwine, Michael ; Rowe, R. Wanda ; Ahn, Chul W. ; Koch, Steven M. / Fever-range whole-body thermal therapy combined with cisplatin, gemcitabine, and daily interferon-α : A description of a phase I-II protocol. In: International Journal of Hyperthermia. 2008 ; Vol. 24, No. 8. pp. 649-662.
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abstract = "Purpose: 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-α). The Phase II component aimed to assess which cancer diagnoses responded to the regimen, the response rate, and response duration. Materials and 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/m2, the cisplatin dose was escalated by 10 mg/m2 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-α. Results: Thirty-seven patients were treated on protocol. The MTD of cisplatin in the thermochemotherapy regimen was established to be 60 mg/m2. 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. Conclusion: 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.",
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AU - Bull, Joan M C

AU - Scott, Glenna L.

AU - Strebel, Frederick R.

AU - Nagle, Verne L.

AU - Oliver, Dwight

AU - Redwine, Michael

AU - Rowe, R. Wanda

AU - Ahn, Chul W.

AU - Koch, Steven M.

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