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Local hyperthermia enhances cyclophosphamide, ifosfamide andcis-diamminedichloroplatinum cytotoxicity on human-derived breast carcinoma and sarcoma xenografts in nude mice

  • Original Papers
  • Experimental Oncology
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Summary

Antitumour response and toxicity of locally applied hyperthermia with or without cyclophosphamide, ifosfamide, andcis-diamminedichloroplatinum (cisplatin) have been compared. The model systems were human breast carcinoma (MX1/3) and human sarcoma (S117) grown in nude mice. In order to detect changes of tumour oxygenation intratumoralPO2 and pH were measured before, during and following hyperthermia. In both human tumour lines a monotherapy with one of the cytotoxic drugs or with hyperthermia caused a transient growth delay, while the combination of the same dose of the drugs with hyperthermia (at 43° C for 1 h) resulted in complete tumour remissions. During hyperthermia, in both tumour types oxygenation was improved. Intratumoral pH remained practically unchanged.

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Abbreviations

CY:

cyclophosphamide

IFO:

ifosfamide

References

  • Bicher HJ, Mitagvaria NP (1984) Changes in tumor tissue oxygenation during microwave hyperthermia. Clinical relevance. In: Overgaard J (ed) Hyperthermic oncology, Taylor and Francis, London, pp 169–172

    Google Scholar 

  • Dahl O (1982) Effects of hyperthermia on a neurogenic rat cell line (BT4A) in vivo. Acta Radiol Oncol 21:67–77

    PubMed  Google Scholar 

  • Dahl O (1988) Hyperthermia and chemotherapy: biological and clinical Studies. In: Issels RD, Wilmanns W (eds) Application of hyperthermia in the treatment of cancer. Springer, Berlin Heidelberg New York, pp 157–169

    Google Scholar 

  • Dahl O, Mella O (1983) Effect of timing and sequence of hyperthermia and cyclophosphamide on a neurogenic rat tumor (BT4A) in vivo. Cancer 52:983–987

    PubMed  Google Scholar 

  • Engelhardt R (1987) Hyperthermia and drugs. In Streffer C (ed) Hyperthermia and the therapy of malignant tumours. Springer, Berlin Heidelberg New York, pp 25–70

    Google Scholar 

  • Engelhardt R, Müller U, Weth-Simon R, Neumann HA, Löhr GW (1990) Treatment of disseminated malignant melanoma with cis-platin in combination with whole body hyperthermia and doxorubicin. Int J Hyperthermia 3:511–515

    Google Scholar 

  • Fisher GA, Hahn GM (1982) Enhancement ofcis-diaminedichloro-platinum (cis-DDP) cytotoxicity by hyperthermia. Natl Cancer Inst Monogr 61:255–257

    Google Scholar 

  • Hahn GM (1982) Hyperthermia and cancer. Plenum, New York

    Google Scholar 

  • Herman TS (1983) Effect of temperature of exposure on the cytotoxicity of three new anticancer drugs. Cancer Treat Rep 67:1019–1022

    PubMed  Google Scholar 

  • Herman TS, Sweets CC, White DM, Gerner EW (1982) Effects of rate of heating on lethality due to hyperthermia and selected chemotherapeutic drugs. J Natl Cancer Inst 68:487–492

    PubMed  Google Scholar 

  • International Consensus Meeting on Hyperthermia (1990) Int J Hyperthermia 6:837–877

    Google Scholar 

  • Issels RD, Prenninger SW, Nagele A, Boehm E, Sauer H, Jauch KW, Denecke H, Berger H, Peter K, Wilmanns W (1990) Ifosfamide plus etoposide combined with regional hyperthermia in patients with locally advanced sarcomas: a phase II study. J Clin Oncol 11:1818–1829

    Google Scholar 

  • Kowal CD, Bertino JR (1979) Possible benefits of hyperthermia to chemotherapy. Cancer Res 39:2285–2289

    PubMed  Google Scholar 

  • Müller-Klieser W, Vaupel P (1984) Effect of hyperthermia on tumor blood flow. Biorheology 21:529–538

    PubMed  Google Scholar 

  • Neumann HA, Fiebig HH, Löhr GW, Engelhardt R (1985) Effects of cytostatic drugs and 40.5° C hyperthermia on human bone marrow progenitors (CFU-C) and human clonogenic tumor cells implanted into mice. J Natl Cancer Inst 75:1059–1066

    PubMed  Google Scholar 

  • Olch AJ, Kaiser LR, Silberman AW, Storm FK, Graham LS, Morton DL (1983) Blood flow in human tumors during hyperthermia therapy: demonstration of vasoregulation and an applicable physiological model. J Surg Oncol 23:125–132

    PubMed  Google Scholar 

  • Overgaard J (1976) Influence of extracellular pH on the viability and morphology of tumor cells exposed to hyperthermia. J Natl Cancer Inst 56:1243–1250

    PubMed  Google Scholar 

  • Reinhold HS, Endrich B (1986) Tumour microcirculation as a target for hyperthermia. Int J Hyperthermia 2:111–137

    PubMed  Google Scholar 

  • Roszinski S, Wiedemann G, Jiang SZ, Baretton G, Wagner T, Weiss C (1991) Effects of hyperthermia and/or hyperglycemia on pH and pO2 in well oxygenated xenotransplanted human sarcoma. Int J Radiat Oncol Biol Physics 20:1273–1280

    Google Scholar 

  • Song CW (1984) Effect of local hyperthermia on blood flow and microenvironment: a review. Cancer Res 44:4721–4730

    Google Scholar 

  • Song CW, Kang MS, Rhee JG, Levitt SH (1980a) The effect of hyperthermia on vascular function, pH, and cell survival. Radiology 137:795–803

    PubMed  Google Scholar 

  • Song CW, Rhee JG, Levitt SH (1980b) Blood flow in normal tissue and tumors during hyperthermia. J Natl Cancer Inst 64:119–124

    PubMed  Google Scholar 

  • Urano M, Rice I, Kalm J, Sedlacek RS (1982) Studies on fractionated hyperthermia in experimental animal systems: I. The foot reaction after equal doses: heat resistance and repopulation. Int J Radiat Oncol Biol Phys 6:1519–1523

    Google Scholar 

  • Urano M, Kahn J, Kenton LA (1990) The effect ofcis-diamminedi-chloroplatinum (II) treatment at elevated temperatures on murine fibrosarcoma, FSa-II. Int J Hyperthermia 6:563–570

    PubMed  Google Scholar 

  • Vaupel P, Frinak S, Mueller-Klieser W, Bicher HI (1982) Impact of localized hyperthermia on the cellular microenvironment in solid tumors. Natl Cancer Inst Monogr 61:207–209

    Google Scholar 

  • Vaupel P, Okunieff P, Kallinowski F, Neuringer LJ (1989) Correlations between31P-NMR spectroscopy and tissue O2 tension measurements in a murine fibrosarcoma. Radiat Res 120:477–493

    PubMed  Google Scholar 

  • Wagner T, Mittendorf F, Wiedemann G (1986) Intracavitary chemotherapy with activated cyclophosphamides and simultaneous systemic detoxification with protector thiols in sarcoma 180 ascites tumor. Cancer Res 46:2214–2219

    PubMed  Google Scholar 

  • Waterman FM, Nerlinger RE, Moylan DJ, Leeper DB (1987) Response of human tumor blood flow to local hyperthermia. Int J Radiat Oncol Biol Phys 13:75–82

    PubMed  Google Scholar 

  • Weiss CH, Fleckenstein W (1986) Local tissue pO2 measured with “thick” needle probes. In: Funktionsanalyse biologischer Systeme. Steiner, Stuttgart, pp 15–155

    Google Scholar 

  • Woo SY, Rice GC, Kapp DS, Hahn GM (1988) A predictive assay for human tumor cellular response to hyperthermia using dansyl lysine staining and flow cytometry. Int J Radiat Oncol Biol Phys 14:361–365

    PubMed  Google Scholar 

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Wiedemann, G., Roszinski, S., Biersack, A. et al. Local hyperthermia enhances cyclophosphamide, ifosfamide andcis-diamminedichloroplatinum cytotoxicity on human-derived breast carcinoma and sarcoma xenografts in nude mice. J Cancer Res Clin Oncol 118, 129–135 (1992). https://doi.org/10.1007/BF01187501

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  • DOI: https://doi.org/10.1007/BF01187501

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