Antitumor activity of Herceptin (R) in combination with STEALTH (R) liposomal cisplatin or nonliposomal cisplatin in a HER2 positive human breast cancer model

Single agent antitumor activity of Herceptin(R), a humanized monoclonal ant ibody directed against HER2, has been demonstrated in numerous preclinical and clinical studies. Additionally, combination therapy with Herceptin and chemotherapy (CRx) has demonstrated additive antitumor activity in both pre clinical models and early clinical trials. STEALTH(R) (pegylated) liposomal (PL) cisplatin; also known as SPI-077, is currently in clinical trials for a variety of solid tumors. The three studies reported here discuss the ant itumor activity of the combination of Herceptin and nonliposomal cisplatin or PL-cisplatin in two xenograft tumor models, initiated from the cell line s, BT474 and MDA453, that overexpress the oncogene, HER2. Herceptin alone h ad significant antitumor activity in all three experiments (p < 0.0001). No nliposomal cisplatin and PL-cisplatin were both effective antitumor agents but, at tolerable dose levels, PL-cisplatin was superior to nonliposomal ci splatin (p < 0.0003). The effect of combining Herceptin with the chemothera peutic cisplatin or PL-cisplatin, was most significant at moderate doses of H (0.5 mg/kg, p < 0.0001), but tended to be greater than either agent alon e in all experiments. The combination of PL-cisplatin with Herceptin had st atistically similar antitumor activity to that of nonliposomal cisplatin wi th Herceptin in all experiments. We conclude that combination therapy with PL-cisplatin and Herceptin results in significant antitumor activity with t he potential for reducing toxicity in metastatic breast cancer patients. (C )1999 Elsevier Science Inc. All rights reserved.