This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Robins, H. I. Articles by Borden, E. C. Search for Related Content PubMed PubMed Citation Articles by Robins, H. I. Articles by Borden, E. C.

Phase I Trial of Human Lymphoblastoid Interferon with Whole Body Hyperthermia in Advanced Cancer¹

University of Wisconsin Clinical Cancer Center, Madison, Wisconsin 53792

Laboratory studies have shown a potentiation of the biological effects of interferons (IFN) by elevated temperatures (39.5–40.5°C). Based on such observations a Phase I clinical trial involving 17 cancer patients was conducted to assess the toxicity and biological effects of combining whole body hyperthermia (WBH) (40.5°C for 75 min) and IFN. The study design incorporated a treatment schedule which allowed comparisons of WBH alone, to IFN administered i.m., to combinations of the two modalities. Human lymphoblastoid IFN was given for 6 days in weeks, 2, 4, and 6. At least 4 patients were entered at each of three IFN dose levels (1 x 10⁶ units/m²; 3 x 10⁶ units/m²; 10 x 10⁶ units/m²). WBH was delivered on day 1 of week 1, day 6 of week 4, and days 4 and 6 of week 6. IFN was administered 1 h prior to WBH. The schedule used allowed for the development of tachyphylaxis to IFN-induced fever. Maximum temperatures were not significantly higher 24 h post-IFN/WBH than after a comparable number of days of human lymphoblastoid IFN alone. There was no statistically significant difference in toxicity assessments, hematological and hepatic blood parameters, serum IFN levels, or biological response modulation (i.e., 2',5'-oligoadenylate synthetase activity; ß₂-microglobulin levels; natural killer cell cytotoxicity, using K562 target cells and Change cells) 24 h posttreatment between human lymphoblastoid IFN alone or combined modality therapy. No cumulative toxicity was observed in 6 patients receiving maintenance therapy for up to 1 year. Prior preclinical observations, together with the clinical safety reported in this study, encourage further investigation into the interactions between IFNs and hyperthermia.

¹ Supported by USPHS Grant RO1-35361-04 and Contract CM07434 awarded by the National Cancer Institute; Department of Health and Human Services NIH Grant RR-03186 from the Division of Research Resources to the University of Wisconsin; and Grant NCI-CM07434. H. I. R. and E. C. B. are supported in part by the American Cancer Society.

² To whom requests for reprints should be addressed, at K4/666 Clinical Science Center, 600 Highland Avenue, Madison, WI 53792.

³ Present address: Biologic Evaluation Section, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD.

Received 8/18/88. Revised 11/10/88. Accepted 12/21/88.

This article has been cited by other articles:

				R. A Vertrees, A. Leeth, M. Girouard, J. D Roach, and J. B Zwischenberger Whole-body hyperthermia: a review of theory, design and application Perfusion, July 1, 2002; 17(4): 279 - 290. [Abstract] [PDF]

				A. Bakhshandeh, V. Bath, G. J Wiedemann, W. Longo, B. M Lerner, C. L Tiggelaar, and H I. Robins Year 2000 guidelines for clinical practice of whole body hyperthermia combined with cytotoxic drugs from the University of Lubeck and the University of Wisconsin Journal of Oncology Pharmacy Practice, September 1, 1999; 5(3): 131 - 134. [PDF]

				S. K Alpard, R. A Vertrees, Weike Tao, D. J Deyo, R. L Brunston JR, and J. B Zwischenberger Therapeutic hyperthermia Perfusion, November 1, 1996; 11(6): 425 - 435. [PDF]