We would like to test our experimental treatment of cancer on nude mice with xenograft tumor, one of our control groups is cisplatin. Our treatment is given to the mice by IV injection three times a day. If someone can supply us the dose and the frequency for cisplatin? From our knowledge cisplatin is given once per week over three weeks. We would like to know if it possible to give cisplatin more frequently?
Check Lauren E. Ta paper @Mayo clinic. 2.3mg/kg cisplatin for 10 days IP (5 days on + 5 days of for 2cycles due to possible renal toxicity. Hope this helps.
The dose has to depend on the clearance rate in the mouse. Humans have a much slower clearance rate so the human dose (in mg/kg) may be way off due to different pharmacokinetics. We can cure cancer in mice because they clear many agents before they become toxic while in humans, the clearance is too slow to permit high doses to be used.I'm sure someone has done this in mice, so check the literature on cis-Pt dosage in mice or better yet, the stain of mouse you plan to used.
If there is no lit on the strain that you are using, do a half-life and ld50 test, the values will be based on the lit. Of similar strains
Here an epub for a nature study just published using single/combo cisplat therapy in nude mice with human tumor xenografts:
Cancer Gene Ther. 2013 Mar 8. doi: 10.1038/cgt.2013.14. [Epub ahead of print]
Enhanced tumor suppression by adenoviral PTEN gene therapy combined with cisplatin chemotherapy in small-cell lung cancer.
Li D, Zhang Y, Xie Y, Xiang J, Zhu Y, Yang J.
Here's another recent one in PLOSOne (open access); they dosed the nudes with cisplat at 3.5 mg/kg, 2x/wk, for 3 wks, once they bore tumors that were 100mm^3 in size.
PLoS One. 2013;8(2):e57391. doi: 10.1371/journal.pone.0057391. Epub 2013 Feb 21.
Klotho Sensitizes Human Lung Cancer Cell Line to Cisplatin via PI3k/Akt Pathway.
Wang Y, Chen L, Huang G, He D, He J, Xu W, Zou C, Zong F, Li Y, Chen B, Wu S, Zhao W, Wu J.
Hope this helps- searching the NLM database at PubMed is usually very fruit-full, especially if you constrain your search using the limiting tools provided. At the end of the day, if you would like to administer a higher or more frequent dose then commonly performed, you need to perform a pilot experiment to explore proof of principle, and answer two important questions: 1) is the increased cisplat causing unacceptable morbidity (usually chemotherapy is administered at or near 1/2 MTD anyway), and 2) why do you think that more cisplat would be a relevant comparison to human therapy, unless your agent somehow decreases the morbidity that would otherwise result from the increased dosing?
Humans receive pre-hydration to offset the acute nephrotoxicity induced by cisplatin. If you are shooting for a treatment regimen with multiple cisplatin doses in the mice (i.p.) you can also pre-hydrate a mouse with an injection of saline (i.p. also), that helps the mouse to cope with higher cisplatin doses.
Hi,
I would like to use Cisplatin model with a single dose in mice ip. However I have difficulty to dissolve the products. I add 25ml of saline 0.9% to 50mg of Cisplatin to have 2mg/mL for in vivo use. We have some precipitate after resuspension. Please do you have some tips ? As well we freeze the solution as it says in the datasheet. Do you if freezing affects the stability of the product ? Thank you very much, Julie
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