A phase I study of pazopanib in combination with FOLFOX 6 or capeOx in subjects with colorectal cancer.
Brady J., Middleton M., Midgley RS., Mallath MK., Corrie P., Sirohi B., Chau I., Digumarti R., Botbyl J., Lager JJ.
4133 Background: Pazopanib (paz) is a tyrosine kinase inhibitor of VEGFR-1, -2, -3, PDGF-α, -β, and c-kit. Inhibition of angiogenic pathways in combination with chemotherapy has been shown to benefit patients (pts) with colorectal cancer (CRC). METHODS: Pts with previously untreated advanced or metastatic CRC and adequate organ function were assigned to paz with FOLFOX6 (FO) or capeOx (CO) by their physician. Doses of paz were escalated with full strength chemotherapy, starting at 400mg daily. The optimally tolerated regimen (OTR) was the combination dose at which <1/6 pts experienced dose-limiting toxicity (DLT). RESULTS: Fifty pts were enrolled in FO (paz 400 mg, n=6; 800, 15), CO (400, 12; 800, 9) and reduced capecitabine (rc) CO (800, 8) cohorts: median age = 55.5, M/F = 37/13. Pts have remained on therapy for a median of 3 (range 0-17) months. Three pts remain on study. Safety data is available on 41. The most common AEs are summarized in the table below. The OTR was exceeded with CO in combination with 800 mg and 400 mg of pazopanib, but was not exceeded with 800 mg pazopanib when capecitabine was reduced to 850 mg/m(2) twice daily or with FO with 800 mg pazopanib. Efficacy and pharmacokinetic analyses are ongoing. CONCLUSIONS: The OTRs were achieved at 800 mg paz with full-dose FO, and at 800mg paz with rcCO. [Table: see text] [Table: see text].