Phase I trial of weekly and every 3 weeks ixabepilone (Ix) and sunitinib (S) in advanced solid tumors (STs).

Profile and potential of ixabepilone in the treatment of pancreatic cancer

“… 26 When ixabepilone was paired with sunitinib, the side effect profile was again similar to that of ixabepilone monotherapy, with the addition of a single event of deep vein thrombosis. 28 While a similar adverse event profile was again seen when dasatinib was combined with ixabepilone, four patients did have to come off study due to drug intolerance before the first efficacy assessment. 29 In the Phase II evaluation of ixabepilone and cetuximab in pancreatic cancer, a similar side effect profile was observed, with the acneiform rash known to occur with cetuximab being the only additional side effect observed.…”

“…Sunitinib, a multitargeted receptor tyrosine kinase inhibitor, is approved for the management of gastrointestinal stromal tumors and renal cell carcinoma, and continues to be investigated in the management of other tumor types. In one study, sunitinib was administered orally at a constant dose in combination with one of two intravenous ixabepilone dose-escalation schedules 28. For these pairings, the maximum tolerated doses were ixabepilone of 20 mg/m 2 (when given on days 1, 8, and 15 in a 28-day cycle) and 30 mg/m 2 (when given on day 1 in a 21-day cycle); in both pairings, sunitinib was administered at a dose of 37.5 mg/m 2 daily, starting on day 8 of cycle 1.…”

“…A similar direct comparison of a combination of ixabepilone and irinotecan versus ixabepilone monotherapy cannot be considered, due to the differing dose schedules between the various trials 26. When ixabepilone was paired with sunitinib, the side effect profile was again similar to that of ixabepilone monotherapy, with the addition of a single event of deep vein thrombosis 28. While a similar adverse event profile was again seen when dasatinib was combined with ixabepilone, four patients did have to come off study due to drug intolerance before the first efficacy assessment 29.…”

“…In one study, sunitinib was administered orally at a constant dose in combination with one of two intravenous ixabepilone dose-escalation schedules. 28 For these pairings, the maximum tolerated doses were ixabepilone of 20 mg/m 2 (when given on days 1, 8, and 15 in a 28-day cycle) and 30 mg/m 2 (when given on day 1 in a 21-day cycle); in both pairings, sunitinib was administered at a dose of 37.5 mg/m 2 daily, starting on day 8 of cycle 1. Tumor types were not reported, and while there were three patients with a partial response and eight with stable disease, none of these responses were seen in patients with pancreatic cancer.…”