Combination chemotherapy involving orally administered etoposide and JM-216 in murine tumor models.
OBJECTIVE
Orally administered VP-16 (etoposide) was evaluated in combination with an orally administered platinum analog, JM-216 [ammine/cyclohexylamine diacetatodichloride Pt(IV)], in mice bearing murine tumors, for therapeutic synergy.


METHODS
The treatment schedules used involved two courses of therapy, each course consisting of administration every day for 5 days beginning on either day 4 or day 5 posttumor implantation, and again on day 11 or day 12 postimplantation.


RESULTS
The amounts of each drug tolerated in the combination treatment setting were much less than their individual maximum tolerated doses (MTDs). Thus, to be used safely, each drug's dose had to be greatly reduced from the amount tolerated when the drugs were given individually. Multiple experiments using a staged P388 leukemia model implanted intravenously yielded confirmatory data supporting the existence of a therapeutic synergy for the drug combination. Identical regimens applied in the staged M5076 sarcoma model implanted subcutaneously, however, were not considered to have yielded data indicative of therapeutic synergy.


CONCLUSIONS
A clinical phase I study using this combination chemotherapy can be recommended on the basis of the results obtained in the leukemia model.
Rose
W C
WC
Pharmaceutical Research Institute, Bristol-Myers Squibb Company, Inc., Lawrenceville, New Jersey, USA.
D000284:Administration, Oral; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005047:Etoposide / Q000008:administration & dosage* / Q000633:toxicity; D005260:Female; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000633:toxicity
D009944:Organoplatinum Compounds; D005047:Etoposide; C081294:satraplatin