Potentiation by Interleukin 1α of Cisplatin and Carboplatin Antitumor Activity: Schedule-dependent and Pharmacokinetic Effects in the RIF-1 Tumor Model

Abstract We have previously demonstrated that the cytokine interleukin 1α (IL-1α) significantly potentiates the antitumor activity of a variety of chemotherapeutic agents, including cisplatin (cDDP). In studies described here, we examined the potential of combining IL-1α and the platinum analogue carboplatin (CBDCA) and compared the schedule-dependent and pharmacokinetic effects for IL-1α combinations with cDDP and CBDCA. RIF-1 tumor-bearing mice (C3H/HeJ) received i.p. injections of varying doses of CBDCA, alone or concurrently with IL-1α (48 or 480 µg/kg). Clonogenic cell kill and tumor regrowth delay were significantly increased when CBDCA was combined with IL-1α, at both doses, compared to either CBDCA or IL-1α alone ( P P P