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Therapeutic efficacy and apoptosis and necrosis kinetics of doxorubicin compared with cisplatin, combined with whole‐body hyperthermia in a rat mammary adenocarcinoma
Author(s) -
Toyota Nobuhiko,
Strebel Frederick R.,
Stephens L. Clifton,
Matsuda Hiroyuki,
Oshiro Tatuso,
Jenkins Gaye N.,
Bull Joan M. C.
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980518)76:4<499::aid-ijc10>3.0.co;2-3
Subject(s) - hyperthermia , apoptosis , doxorubicin , medicine , cisplatin , necrosis , chemotherapy , pharmacology , biology , biochemistry
We have compared the therapeutic efficacy as well as the kinetics of treatment‐induced apoptosis and necrosis of the maximum tolerated dose (MTD) of doxorubicin (DOX) or cisplatin (CDDP) combined with long‐duration, low‐temperature whole‐body hyperthermia (LL‐WBH, at 40.0°C for 6 hr), with the combination of the MTDs of either DOX or CDDP with short‐duration, high‐temperature WBH (SH‐WBH, at 41.5°C for 2 hr), in a rat mammary adenocarcinoma (MTLn3). The MTD of LL‐WBH + DOX resulted in increased therapeutic efficacy, compared with the MTD of DOX alone and SH‐WBH + DOX. The MTD of LL‐WBH + CDDP, however, did not increase therapeutic efficacy, when compared with the MTD of CDDP alone or SH‐WBH + CDDP. The MTD of LL‐WBH + DOX caused a significant delay in the development of spontaneous axillary lymph node (ALN) metastasis and tended to cause longer mean survival, compared with SH‐WBH + DOX. The peak of treatment‐induced apoptosis was higher for the MTD of DOX + LL‐WBH, compared with SH‐WBH + DOX, whereas the apoptosis peak of the MTD of SH‐WBH + CDDP was higher than that of LL‐WBH + CDDP. The most extensive levels of tumor necrosis appeared to occur earlier with SH‐WBH alone and the MTD of SH‐WBH + DOX or CDDP than with other groups. Our results suggest that LL‐WBH + DOX may be a promising therapy for breast cancer, and the extent of treatment‐induced tumor apoptosis appears to correlate with antitumor response for MTDs of LL‐WBH + DOX and SH‐WBH + DOX, but not for the MTDs of CDDP with SH‐WBH or LL‐WBH. Int. J. Cancer 76:499–505, 1998.© 1998 Wiley‐Liss, Inc.