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Wirkung der lokalen moderaten Hyperthermie in Kombination mit N-Nitroso-1,3-bis-(2-chlorethyl)-harnstoff (BCNU) und 5-Fluor-(tetrahydro-2-furyl)-uracil (Ftorafur) auf induzierte autochthone Coloncarcinome der Ratte

3. Mitteilung: Polychemotherapie in Kombination mit Hyperthermie

Effect of moderate local hyperthermia in combination with N-nitroso-1,3-bis(2-chloroethyl)urea (BCNU) and 5-fluoro(tetra hydro-2-furyl)uracil (ftorafur) on induced autochthonous colonic carcinomas in rats

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Summary

The use of hyperthermia for the treatment of tumors has been tested in in vitro and in vivo experiments as well as clinically for a long time. Combination of hyperthermia with chemotherapy was reported to result in overadditive cytostatic effects. In a clinically adapted, controlled animal experiment, local moderate hyperthermia (43.5°C, 3 × 60 min) alone and in combination with polychemotherapy (BCNU and Ftorafur) was used for the treatment of AMMN-(N-nitrosoacetoxymethyl-methylamine) induced autochthonous colonic carcinomas in Sprague-Dawley rats. Diagnosis and follow-up inspections were carried out endoscopically. The applied therapies did not result in prolonged survival times, nor was an additive effect seen after combined hyperthermia and chemotherapy in this “hard”, i. e. relatively chemotherapy-resistent, tumor model.

Zusammenfassung

Hyperthermie zur Behandlung von Tumoren wird seit längerem in In-vitro- und In-vivo-Versuchen und auch in der Klinik in verschiedenen Anwendungsformen erprobt. Bei der Kombination von Hyperthermie mit Chemotherapie wird eine überadditive cytostatische Wirkung beschrieben. In einem klinisch orientierten, kontrolliert durchgeführten Tierversuch wurde an einem durch N-Nitrosoacetoxymethylmethylamin (AMMN) induzierten autochthonen Coloncarcinom bei Sprague-Dawley-Ratten eine lokale, moderate Hyperthermie (43,5°C, 3 × 60 min) und eine Kombinationsbehandlung von Hyperthermie und Polychemotherapie (BCNU und Ftorafur) durchgeführt unter endoskopischer Diagnosestellung und Verlaufskontrolle. Es konnte keine Überlebenszeitverlängerung durch die angewendeten Therapien und keine additive Wirkung der lokalen moderaten Hyperthermie in Kombination mit der Chemotherapie bei diesem „harten”, d. h. relativ chemotherapieresistenten, Tumormodell gesehen werden.

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Literatur

  1. Barlogie B, Corry PM, Drewinko B (1980) In vitro thermochemotherapy of human colon cancer cells with cis-dichlorodiammineplatinum (II) and Mitomycin C. Cancer Res 40:1165–1168

    PubMed  Google Scholar 

  2. Blair RM, Levin W (1977) Clinical experience of the induction and maintenance of whole-body hyperthermia. In: Streffer C et al (eds) Cancer therapy by hyperthermia and radiation. Proceedings of the Second International Symposium, Essen, Germany, p 318–321

  3. Busch W (1866) Über den Einfluß, welchen heftigere Erysipeln zuweilen auf organisierte Neubildungen ausüben. Verh Naturh Preuss Rhein Westphal 23:28–30

    Google Scholar 

  4. Cavaliere R, Ciocatto EC, Giovanella BC, Heidelberger Ch, Johnson RO, Margottini M, Mondovi B, Moricca G, Rossi-Fanelli A (1967) Selective heat sensitivity of cancer cells. Cancer 20:1351–1381

    PubMed  Google Scholar 

  5. Cavaliere R, Moricca G, Di Filippo F, Aloe L, Monticelli G, Sartori FS (1981) Hyperthermic perfusion 16 years after its first clinical application. Henry Ford Hosp Med J 29:32–36

    PubMed  Google Scholar 

  6. Dahl O (1980) Effects of hyperthermia on a neurogenic rat cell line (BT4C) in culture. Acta Radiol Oncol 19:489–496

    PubMed  Google Scholar 

  7. 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 

  8. Eisenbrand G, Fiebig HH, Zeller WJ (1976) Some new congeners of the anticancer agent 1,3-bis-(2-chloroethyl)-1-nitrosurea (BCNU). Synthesis of bifunctional analogs and water soluble derivatives and preliminary evaluation of their chemotherapeutic potential. Z Krebsforsch 86:279–286

    Google Scholar 

  9. Fehleisen F (1883) Aetiologie des Erysipels, 21–30. Verlag von Theodor Fischer's Medicinischer Buchhandlung, Berlin

    Google Scholar 

  10. Fox RM, Woods RL, Tattersall MHN (1979) Allopurinol modulation of high-dose fluorouracil toxicity. Cancer Treat Rev 6:143–147

    PubMed  Google Scholar 

  11. Giovanella BC, Morgan AC, Stehlin JS, Williams LJ (1973) Selective lethal effect of supranormal temperatures on mouse sarcoma cells. Cancer Res 33:2568–2578

    PubMed  Google Scholar 

  12. Giovanella BC, Stehlin JS, Morgan AC (1976) Selective lethal effect of supranormal temperatures on human neoplastic cells. Cancer Res 36:3944–3950

    PubMed  Google Scholar 

  13. Habs M, Schmähl D (1976) On the carcinogenicity of acetoxymethyl-methyl-nitrosoamine by different routes of application in rats. Med Biol Environ 4:205–210

    Google Scholar 

  14. Habs M, Schmähl D (1978) Experimental testing of chemotherapeutic agents in autochthonous tumors with special reference to colorectal cancer. In: Grundmann E (ed) Cancer campaign, Vol 2, Colon cancer. Fischer, Stuttgart, p 217–226

    Google Scholar 

  15. Habs M (1981) Methoden, Ergebnisse und Probleme der experimentellen Chemotherapie. In: Schmähl D (Hrsg) Maligne Tumoren. Entstehung, Wachstum und Chemotherapie. Editio Cantor, Aulendorf, 3. Aufl, S 455–498

    Google Scholar 

  16. Hafström L, Jönssen PE (1980) Hyperthermic perfusion of recurrent malignant melanome on the extremities. Acta Chir Scand 146:313–318

    PubMed  Google Scholar 

  17. Hahn GM (1979) Potential for therapy of drugs and hyperthermia. Cancer Res 39:2264–2268

    PubMed  Google Scholar 

  18. Herman TS, Zukoski CF, Anderson RM, Hutter JJ, Blitt CD, Malone JM, Larson DF, Dean JC, Roth HB (1982) Whole-body hyperthermia and chemotherapy for treatment of patients with advanced, refractory malignancies. Cancer Treat Rep 66:259–265

    PubMed  Google Scholar 

  19. Kase K, Hahn GM (1975) Differential heat response of normal and transformed human cells in tissue culture. Nature 255:228–230

    PubMed  Google Scholar 

  20. Koga S, Izumi A, Maeta M, Shimizu N, Osaki Y, Kanayama H (1983) The effects of total-body hyperthermia combined with anticancer drugs on immunity in advanced cancer patients. Cancer 52:1173–1177

    PubMed  Google Scholar 

  21. Lange J, Zänker KS, Siewert JR, Eisler K, Landauer B, Kolb E, Blümel G, Remy W (1983) Extrakorporal induzierte Ganzkörperhyperthermie bei konventionell inkurablen Malignompatienten. Dtsch Med Wochenschr 108:504–509

    PubMed  Google Scholar 

  22. Lavin P, Mittelman A, Douglass H, Engstrom P, Klaassen D (1980) Survival and response to chemotherapy for advanced colorectal adenocarcinoma. Cancer 46:1536–1543

    PubMed  Google Scholar 

  23. Lorenz M, Habs M, Schmähl D (1983) Wirkung der lokalen moderaten Hyperthermie in Kombination mit einer Chemotherapie durch Cyclophosphamid oder N-Nitroso-1,3-bis-(2-chlorethyl)harnstoff (BCNU) auf das in das Colon descendens der Ratte transplantierte Yoshida-Sarkom. 1. Mitteilung: Zweimalige Hyperthermie im Abstand von 8 Tagen sowie Kombination von Chemotherapie mit 24 h später folgender Hyperthermie. Langenbecks Arch Chir 359:205–213

    PubMed  Google Scholar 

  24. Lorenz M, Biwer E, Habs M, Schmähl D. Wirkung der lokalen moderaten Hyperthermie in Kombination mit einer Chemotherapie durch N-Nitroso-1,3-bis-(2-chloroethyl)-harnstoff(BCNU) auf das in das Colon descendens der Ratte transplantierte Yoshida-Sarkom. 2. Mitteilung: Monochemotherapie in Kombination mit nachfolgender Hyperthermie in unterschiedlichen Zeitintervallen. Langenbecks Arch Chir362:253–261

  25. Marmor JB (1979) Interactions of hyperthermia and chemotherapy in animals. Cancer Res 39:2269–2276

    PubMed  Google Scholar 

  26. Merz R, Wagner I, Habs M, Schmähl D (1981) Endoscopic diagnosis of chemically induced autochthonous colonic tumors in rats. Hepato-Gastroenterol 28:53–57

    Google Scholar 

  27. Narisawa T, Wong ChQ, Weisburger JH (1975) Evaluation of endoscopic examination of colon tumors in rats. Dig Dis 20:928–934

    Google Scholar 

  28. Overgaard J, Suit HD, Walker AM (1980) Multifractionated hyperthermia treatment of malignant and normal tissue in vivo. Cancer Res 40:2045–2050

    PubMed  Google Scholar 

  29. Peto R (1974) Guidelines on the analysis of tumor rates and death rates in experimental animals. Br J Cancer 29:101–105

    PubMed  Google Scholar 

  30. Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV, Mantel N, McPherson K, Peto J, Smith PG (1977) Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples. Br J Cancer 35:1–39

    PubMed  Google Scholar 

  31. Pettigrew RT, Ludgate CM, Gee AP, Smith AN (1977) Whole body hyperthermia combined with chemotherapy in the treatment of advanced human cancer. In: Streffer et al (eds) Cancer therapy by hyperthermia and radiation. Proceedings of the Second International Symposium, Essen, Germany, p 337–339

  32. Pinedo HM (1979) Cancer chemotherapy 1979. EORTC Cancer Chemotherapy Annual 1. Excerpta Medica, Amsterdam, New York

    Google Scholar 

  33. Queisser W, Heim ME (1981) Chemotherapy in alimentary tract malignoma. Hepato-Gastroenterol 28:275–283

    Google Scholar 

  34. Schmähl D (1976) Utilisation of nitrosamine-induced tumors as models for cancer chemotherapy. 233–238 In: Hellmann K, Connors TA (eds) Chemotherapy, Vol. 7. Plenum Publishing Corporation, New York, p 233–338

    Google Scholar 

  35. Schmähl D (Hrsg) (1981) Maligne Tumoren. Entstehung, Wachstum, Chemotherapie. 3. Aufl, Editio Cantor, Aulendorf

    Google Scholar 

  36. Shiu MH, Fortner JG (1980) Intraperitoneal hyperthermic treatment of implanted peritoneal cancer in rats. Cancer Res 40:4081–4084

    PubMed  Google Scholar 

  37. Smith GV, MacMillan R, Strobling J (1983) Intraperitoneal approach to regional hyperthermia — Possible anticancer applications. World J Surg 7:732–737

    PubMed  Google Scholar 

  38. Spratts JS, Adcock RA, Muskovin M, Sherill W, McKeown J (1980) Clinical delivery system for intraperitoneal hyperthermic chemotherapy. Cancer Res 40:256–260

    PubMed  Google Scholar 

  39. Stehlin JS, Giovanella BC, de Ipolyi PD, Anderson RF (1979) Eleven years' experience with hyperthermic perfusion for melanoma of the extremities. World J Surg 3:305

    PubMed  Google Scholar 

  40. Sych F, Habs M, Schmähl D (1978) Chemotherapy studies in autochthonous rat tumors. Intestinal cancer. Z Krebsforsch 92:105–117

    Google Scholar 

  41. Urano M, Rice L, Epstein R, Suit HD, Chu AM (1983) Effect of whole-body hyperthermia on cell survival, metastasis frequency, and host immunity in moderately and weakly immunogenic murine tumors. Cancer Res 43:1039–1043

    PubMed  Google Scholar 

  42. Wagner I, Habs M, Schmähl D, Amberger H, Bachmann U (1982) Chemotherapeutic studies on N-nitrosoacetoxymethyl-methylamine and 1,2-dimethyl-hydrazine-induced colonic tumors in rats: Monotherapy with 5-fluoruracil. Ftorafur, CGP 6809 and CGP 15′720A. J Cancer Res Clin Oncol 104:115–131

    PubMed  Google Scholar 

  43. Wiessler M (1975) Chemie der Nitrosamine II. Synthese α-funktioneller Dimethylnitrosamine. Tetrahedron Lett 30: 2575–2578

    Google Scholar 

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Authors and Affiliations

  1. Institut für Toxikologie und Chemotherapie, Deutsches Krebsforschungszentrum Heidelberg, Im Neuenheimer Feld 280, D-69110, Heidelberg

    E. Biwer, M. Lorenz, M. Habs & D. Schmähl

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  1. E. Biwer
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  2. M. Lorenz
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  3. M. Habs
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  4. D. Schmähl
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Biwer, E., Lorenz, M., Habs, M. et al. Wirkung der lokalen moderaten Hyperthermie in Kombination mit N-Nitroso-1,3-bis-(2-chlorethyl)-harnstoff (BCNU) und 5-Fluor-(tetrahydro-2-furyl)-uracil (Ftorafur) auf induzierte autochthone Coloncarcinome der Ratte. Langenbecks Arch Chiv 363, 5–15 (1984). https://doi.org/10.1007/BF01255773

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