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in vitro thermo-chemosensitivity screening of spontaneous human tumors: Significant potentiation for cisplatin but not adriamycin

✍ Scribed by Annamaria Calabro; S. Eva Singletary; Susan Tucker; Arthur Boddie; Gary Spitzer; Renato Cavaliere


Book ID
102868547
Publisher
John Wiley and Sons
Year
1989
Tongue
French
Weight
638 KB
Volume
43
Category
Article
ISSN
0020-7136

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✦ Synopsis


The in vitro thermal enhancement of Adriamycin (ADR) and Cisplatin (CDDP) was investigated in 18 surgical biopsy specimens of human tumors cultured in the Adhesive Tumor Cell Culture System. Experimental conditions were adopted to simulate "therapeutic" trials: (a) temperature of 37.0°C, 40.5"C or 42.5OC; (b) hyperthermic duration of 30,60, or I20 min; and (c) 4-dose drug range normalized to human bone marrow toxicity. Drug concentrations that inhibited 90% of tumor growth (IC,) at 37.0% were compared to the IC, at 40.5"C and 42.5"C, adjusted for the effect of heat alone. CDDP plus heat was a better combination than ADR plus heat, regardless of the temperature and the exposure duration: significant synergism (p < 0.001) occurred in 37% of heat-CDDP combinations, as compared with 15% of heat-ADR combinations, and antagonism was significantly lower <g < 0.001) for heat-CDDP than for heat-ADR (4.4% versus 21 /o of combinations, respectively). Within the CDDP group, higher temperature and longer heat exposure resulted in an increased incidence of chemosensitivity. No specific pattern of synergism was evident within the ADR group, but a trend toward a higher incidence of antagonistic effects with increasing hyperthermic duration was observed.