Hyperthermia enhances the cytotoxicity and platinum-DNA adduct formation of lobaplatin and oxaliplatin in cultured SW 1573 cells

Abstract

Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Abstract The cytotoxicity of cisplatin and cisplatin-DNA adduct formation in vitro and in vivo is clearly enhanced by hyperthermia. We investigated whether cytotoxicity and platinum-DNA adduct formation of two promising new third-generation platinum derivatives, lobaplatin [1,2-diamminomethylcyclobutane platinum(II) lactate] and oxaliplatin [oxalato-l,2-diaminocyclohexane platinum(II)], are also enhanced by hyperthermia. Cisplatin was used for comparison. SW 1573 cells were incubated with cisplatin, lobaplatin or oxaliplatin at different concentrations for 1 h at 37 ~ 41 ~ and 43~ The reproductive capacity of cells was determined by cloning experiments. Immunocytochemical detection of platinum-DNA adducts was performed with the rabbit antiserum NKI-A59. At 37~ cisplatin was the most cytotoxic, followed by oxaliplatin and lobaplatin. Hyperthermia clearly enhanced the cytotoxicity of cisplatin, lobaplatin and oxaliplatin. There was no further increase in cytotoxicity at 43~ compared to 41~ for cisplatin and oxaliplatin. A further increase in cytotoxicity at 43~ was observed for lobaplatin. At 43~ thermal enhancement was higher for lobaplatin than for oxaliplatin, with the reverse pattern at 41~ For both drugs, thermal enhancement of cytotoxicity was lower than observed for cisplatin. Immunocytochemical detection of platinum-DNA adducts was feasible for all the drugs. Adduct formation was enhanced at 43~ for cisplatin, lobaplatin and oxaliplatin with a relative increase of 410%, 170% and 180%. These results seem to confirm that an increase in platinum-DNA adduct formation is involved in the in vitro thermal enhancement of cytotoxicity. The observed thermal enhancement of cytotoxicity of lobaplatin and oxaliplatin in vitro warrants further in vivo investigations.

Human Pharmacokinetic Study of Heated Intraperitoneal Oxaliplatin in Increasingly Hypotonic Solutions after Complete Resection of Peritoneal Carcinomatosis

“…LOHP is currently the most interesting drug for local use with hyperthermia for colorectal carcinoma [10]. It has the highest response rate of a single agent in intravenous second-line therapy (24% of patients with metastases) [13].…”

“…chemotherapy must be immediate to avoid trapping residual tumor cells in postoperative fibrin adhesions [6, 7]. IPCH leads to high local concentrations of antineoplastic agents [8, 9]and their cytotoxicity is improved by hyperthermia [8, 9]; for example, oxaliplatin (LOHP) cytotoxicity increases by 180% [10]. IPCH was superior to i.p.…”

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in recurrent ovarian cancer with peritoneal metastasis: a prospective registry study on 41 patients

“…HIPEC combines the regional pharmacokinetic advantage of the intraperitoneal drug delivery with the enhanced cytotoxicity of the drug by heat [19,20]. CRS and HIPEC have been evaluated in the primary, advanced and recurrent ovarian cancer settings [21].…”

Peritoneal Carcinomatosis

“…From first demonstrations of the rationale [152] and the pharmacokinetic [153] during hyperthermic application, few phase Ⅱ trials included OXt in their protocols [145,154] . In particular, Elias et al [133] published a series of 24 patients treated with Oxaliplatin in the perfusate at 460 mg/m 2 in 2 L/m 2 , during 30 min at 43 ℃ and later a revised protocol including 106 consecutive patients treated with lower dose of oxaliplatin (360 mg/m 2 ) combined with irinotecan (360 mg/m 2 ) in 2 L/m 2 of 5% dextrose, for the same time at 43 ℃.…”