TY - JOUR
T1 - Fever-range whole-body thermal therapy combined with cisplatin, gemcitabine, and daily interferon-α
T2 - A description of a phase I-II protocol
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.
N1 - Funding Information:
This clinical investigation was carried out in the University of Texas Medical School at Houston and the study was supported in part by NIH grant #M01-RR 02558 through the University General Clinical Research Center (GCRC).
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
KW - Cisplatin
KW - Fever-range whole-body thermal therapy (FR-WB-TT)
KW - Gemcitabine
KW - Interferon-α (IFN-α)
KW - Optimized timing/schedule
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U2 - 10.1080/02656730802104740
DO - 10.1080/02656730802104740
M3 - Article
C2 - 18608594
AN - SCOPUS:57649229038
SN - 0265-6736
VL - 24
SP - 649
EP - 662
JO - International Journal of Hyperthermia
JF - International Journal of Hyperthermia
IS - 8
ER -