Response of murine tumors to matrix-associated cisplatin intratumoral implants

The response to collagen matrix-associated cisplatin (cis-DDP-CM) implanted intratumorally into KHT and RIF-1 fibrosarcomas grown sc in C3H mice was studied. The effects on tumor growth as well as body weight and animal survival were assessed. The effect of cis-DDP-CM (8 mg/kg) on the growth of KHT tumor was assessed by determining the number of days required for tumors to grow to three times the pretreatment volume of 100-150 mm3. When cisplatin (cis-DDP) was administered ip, the number of days required for threefold growth was 11.1 +/- 2.5 SE. Administration of cis-DDP-CM intratumorally resulted in a value of 17.2 +/- 1.7 days. Epinephrine (0.1-5.0 mg/kg) was also added to the matrix as a vasoconstrictor to further localize the activity of cis-DDP. This resulted in enhanced antitumor activity and, presumably, lower systemic exposure to cis-DDP. For cis-DDP administered ip, the dose required to kill 50% of the test group at 10 days after injection was approximately 14 mg/kg. When cis-DDP-CM was administered intratumorally in doses less than or equal to 30 mg/kg, no mice died. Loss in mouse body weight (greater than 3 g) was detected with ip doses of cis-DDP at 8 mg/kg, but no weight loss was detected for mice treated with matrix implant delivering cis-DDP doses less than or equal to 25 mg/kg.