Metastatic colorectal cancer ( mCRC ) is commonly treated with 5-Fluorouracil, Folinic acid, and Oxaliplatin or Irinotecan.
The multitargeted kinase inhibitor, Regorafenib ( Stivarga ), was combined with chemotherapy as first- or second-line treatment of metastatic colorectal cancer to assess safety and pharmacokinetics ( primary objectives ) and tumor response ( secondary objective ).
Forty-five patients were treated every 2 weeks with 5-Fluorouracil 400 mg/m2 bolus then 2400 mg/m2 over 46 h, Folinic acid 400 mg/m2, and either Oxaliplatin 85 mg/m2 or Irinotecan 180 mg/m2.
On days 4-10, patients received Regorafenib 160 mg orally once daily.
The median duration of treatment was 108 ( range 2-345 days ).
Treatment was stopped for adverse events or death ( 17 patients ), disease progression ( 11 patients ), and consent withdrawal or investigator decision ( 11 patients ).
Six patients remained on Regorafenib at data cutoff ( two without chemotherapy ).
Drug-related adverse events occurred in 44 patients [ grade greater than or equal to 3 in 32 patients: mostly neutropenia ( 17 patients ) and leukopenia, hand-foot skin reaction, and hypophosphatemia ( four patients each ) ].
Thirty-three patients achieved disease control ( partial response or stable disease ) for a median of 126 ( range 42-281 days ).
In conclusion, Regorafenib had acceptable tolerability in combination with chemotherapy, with increased exposure of Irinotecan and SN-38 but no significant effect on 5-Fluorouracil or Oxaliplatin pharmacokinetics. ( Xagena )
Schultheis B et al, Ann Oncol 2013;24:1560-1567