Effect of Bleomycin and Liblomycin Combined With Whole Body Hyperthermia on Tumor and Normal Tissue in Rats

Ohno, Sho; Strebel, F. R.; Stephens, L. Clifton; Siddik, Zahid H.; Jenkins, G. C.; Bull, J. M.

doi:10.1016/b978-0-12-168561-4.50965-3

Cited by 15 publications

(19 citation statements)

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“…Determination of peripheral blood cell counts White blood cell (WBC), red blood cell (RBC) and platelet counts were determined on a Coulter Counter (model ZM, Coulter Electronics, Inc., Hialeah, FL), as described previously (Siddik et al, 1987;Ohno et al, 1991 . These rats were sacrificed on day 3, 5 or 7 after treatment, and the organs were processed for light microscopic evaluation as previously described .…”

Section: Haematological Toxicitymentioning

confidence: 99%

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Haematological toxicity of carboplatin and cisplatin combined with whole body hyperthermia in rats

Ohno¹,

Strebel²,

Stephens³

et al. 1993

Br J Cancer

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Summary Acute haematological toxicity induced by cis-diammine-1,1-cyclobutane dicarboxylate platinum (II) (carboplatin) and cis-diamminedichloroplatinum (II) (cisplatin) in combination with whole body hyperthermia (WBH) (2 h at 41.5°C) was examined using a F344 rat model. The thermal enhancement ratios (TERs) of drug-mediated thrombocytopenia, anaemia and leukopenia were determined from the dose-response curves of the nadir values of the peripheral platelet, RBC and WBC counts. Carboplatin produced profound depression of platelet counts which was over three-fold greater than cisplatin (14% vs 51% of the control), while the decrease in WBC and RBC counts induced by carboplatin did not differ significantly from those observed with cisplatin. These carboplatin or cisplatin-mediated haematological toxicities were significantly enhanced by WBH. The depth of decrease in platelet, RBC and WBC counts induced by the maximum tolerated dose (MTD) of carboplatin (30 mg kg-1) combined with WBH was identical to that induced by the MTD of carboplatin (70 mg kg-') alone. The TERs of carboplatin-mediated thrombocytopenia, anaemia and leukopenia were 2.0, 2.8 and 1.9, respectively. The thermal enhancement of cisplatin mediated haematological toxicity was similar to that of carboplatin, with TERs of 1.8 for thrombocytopenia, 2.4 for anaemia and 1.9 for leukopenia. These data, demonstrating thermal enhancement of cisplatin or carboplatin-mediated haematological toxicity, must be taken into account in the clinical application of the combination thereapy of platinum and WBH.Hyperthermia has been shown to increase the cytotoxicity of cisplatin (Hahn, 1979;Barlogie et al., 1980), a chemotherapeutic agent commonly used for wide spectrum of human malignancies (Durant, 1980;Zwelling, 1987). At normal temperature, the clinical use of cisplatin is limited by severe toxicity to several normal tissues, especially the kidney, the gastrointestinal tract, and the bone marrow (Rose et al., 1982;Von Hoff et al., 1979). Simultaneous application of cisplatin during WBH produces unacceptable renal toxicity in humans as well as in experimental animals (Gerard et al., 1983;Bull, 1984;Mella et al., 1987). Our previous studies demonstrated that administration of cisplatin combined with WBH caused a 3-fold increase in renal injury, resulting in a limited therapeutic gain of this combined modality .Carboplatin is a new platinum complex with a similar spectrum of antitumour activity as cisplatin (Wagstaff et al., 1989). The major advantage of carboplatin is that it produces minimal or no nephrotoxicity. The dose-limiting toxicity of this analog is myelosuppression, mainly in form of thrombocytopenia (Harrap et al., 1980;Calvert et al., 1982;Wiltshaw, 1985). As observed with cisplatin, the cytotoxicity of carboplatin was also enhanced when combined with hyperthermia in vitro (Cohen & Robbins, 1987;Xu & Alberts, 1988 The purpose of this study is therefore, to examine the severity of thrombocytopenia, anaemia and leukopenia induced by carboplatin or cisplatin...

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Section: Haematological Toxicitymentioning

confidence: 99%

“…Carboplatin was synthesised in-house as described previously (Baer et al, 1985;Khokhar et al, 1988;Ohno et al, 1991). Carboplatin and cisplatin (Platinol; Bristol Myers, Syracuse, NY) were dissolved in 5%-Dextrose in water and in sterile water, respectively, immediately prior to use.…”

Section: Drugsmentioning

confidence: 99%

Haematological toxicity of carboplatin and cisplatin combined with whole body hyperthermia in rats

Ohno¹,

Strebel²,

Stephens³

et al. 1993

Br J Cancer

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“…Many studies have reported synergistic antitumor response when hyperthermia was simultaneously combined with either DOX or CDDP in tumor models (Hahn and Strande, 1976;Barlogie et al, 1980;Baba et al, 1989). Previously, we reported the antitumor and normal tissue effects of SH-WBH (41.5°C for 2 hr) combined simultaneously with a number of cytotoxic drugs (Ohno et al, 1991;Wondergem et al, 1988a). Therapeutic gain was limited by SH-WBH enhancement of normal tissue toxicity.…”

mentioning

confidence: 99%

Therapeutic efficacy and apoptosis and necrosis kinetics of doxorubicin compared with cisplatin, combined with whole-body hyperthermia in a rat mammary adenocarcinoma

Toyota

Strebel²,

Stephens

et al. 1998

Int. J. Cancer

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“…Hyperthermia is one modality which increases the therapeutic effects of various anticancer drugs [1][2][3] and may have a supportive role to circumvent drug resistance, one of the reasons for the ineffectiveness of chemotherapy [4,5]. For these reasons, many institutes have applied hyperthermia to treat patients with various forms of malignancies, locally [6] and systematically [7][8][9], In our institute we have applied 43 °C hyperthermia in combina tion with chemotherapy -c/s-diamminedichloroplatinum(II) (CDDP) or bleomycin -and radiation against esophageal cancer [10,11].…”

Section: -Smentioning

confidence: 99%

Interaction of cis-Diamminedichloro-platinum(ll) and Its Analogues cis-1,1-Cyclobutanedicarboxylato(2R)-2-Methyl-1,4 Butanediammineplatinum(ll) and cis-Diammine(glycolato)platinum with Hyperthermia in vivo

et al. 1996

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The interaction of cis-1,1-cyclobutanedicarboxylato(2R)-2-methyl-1,4-buta-nediammineplatinum(II) (NK121) and ds-diammme(glycolato)platinum(II) (254-S), analogues of cis-diamminedichloroplatinum(II) (CDDP), with hyperthermia was examined in vivo. Antitumor activity of the platinum complexes at the maximum tolerated dose (MTD) with or without hyperthermia was evaluated by the tumor growth delay assay using B16F10 melanoma growing in the legs of C57BL/6J mice. MTD of CDDP, NK121 or 254-S at the single intraperitoneal injection with hyperthermia was 8, 50 or 30 mg/kg, respectively. Treatment of the tumor-bearing limb at 43 °C for 30min resulted in a tumor growth delay of 1.1 days. A single dose of CDDP produced a 3.3-day tumor growth delay. When CDDP was injected just before hyperthermia (43°C, 30 min), the growth delay increased to 5.5 days (1.7-fold increase). With NK121, there was a 1.5-day growth delay. In combination with hyperthermia, the tumor growth delay by NK121 was 3.2 days (2.1-fold increase). Injection of 254-S led to a growth delay of 3.5 days, and this delay was extended to 5.7 days (1.6-fold increase) when combined with hyperthermia. Changes in serum blood urea nitrogen (BUN) were determined 5 days after intraperitoneal drug administration with or without hyperthermia. A single administration of CDDP 8 mg/kg resulted in an elevated BUN level, and this was enhanced in combination with hyperthermia (66.3 mg/dl, 2.7-fold over control). NK121 50 mg/kg at 37°C did not result in elevation of BUN, but mild nephrotoxicity was noted in combination with hyperthermia (40.3 mg/ dl, 1.6-fold increase over control). The administration of 254-S 30 mg/kg resulted in an elevated BUN level, and this elevation was enhanced in combination with hyperthermia (48.6 mg/dl, 2.0-fold increase over control). Our data showed that NK121 and 254-S as well as CDDP produced greater tumor growth delay together with hyperthermia than did the drug alone. Though these new compounds were designed with reduced nephrotoxicity, attention should be paid to increased nephrotoxicity when combined with hyperthermia.

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Effect of Bleomycin and Liblomycin Combined With Whole Body Hyperthermia on Tumor and Normal Tissue in Rats

Cited by 15 publications

References 0 publications

Haematological toxicity of carboplatin and cisplatin combined with whole body hyperthermia in rats

Haematological toxicity of carboplatin and cisplatin combined with whole body hyperthermia in rats

Therapeutic efficacy and apoptosis and necrosis kinetics of doxorubicin compared with cisplatin, combined with whole-body hyperthermia in a rat mammary adenocarcinoma

Interaction of <i>cis</i>-Diamminedichloro-platinum(ll) and Its Analogues <i>cis</i>-1,1-Cyclobutanedicarboxylato(2R)-2-Methyl-1,4 Butanediammineplatinum(ll) and <i>cis</i>-Diammine(glycolato)platinum with Hyperthermia in vivo

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