Safety and Pharmacokinetics of Second-line Ramucirumab plus FOLFIRI in Japanese Patients with Metastatic Colorectal Carcinoma.

BACKGROUND: This phase Ib study evaluated the pharmacokinetic profile and safety of ramucirumab, a recombinant human IgG1 neutralizing monoclonal antibody specific for vascular endothelial growth factor receptor 2, in combination with irinotecan, levofolinate and 5-fluorouracil (FOLFIRI) in Japanese patients with metastatic colorectal carcinoma (mCRC). PATIENTS AND METHODS: Eligible patients had Eastern Cooperative Oncology Group performance status 0-1, and disease progression during or within 6 months following first-line therapy with bevacizumab, oxaliplatin and a fluoropyrimidine. Six enrolled patients received 8 mg/kg ramucirumab plus FOLFIRI every 2 weeks. RESULTS: One out of six patients experienced a dose-limiting toxicity (grade 2 proteinuria and grade 4 neutropenia, resulting in a dose delay >2 weeks). All patients experienced at least one grade 3 or higher adverse event: neutropenia (five patients, 83%), proteinuria (two patients; 33%) and anemia, thrombocytopenia and hypertension (one patient each, 17%). There were no serious adverse events or deaths. CONCLUSION: Ramucirumab plus FOLFIRI was well-tolerated in Japanese patients with mCRC, warranting further investigation of this combination therapy.