Takayuki Yoshino1, Kentaro Yamazaki2, Masahiro Gotoh3, Federico Nasroulah4, Ling Gao4, Naoto Yoshizuka5, Atsushi Ohtsu6. 1. National Cancer Center Hospital East, Kashiwa, Japan tyoshino@east.ncc.go.jp. 2. Shizuoka Cancer Center, Shizuoka, Japan. 3. Osaka Medical College Hospital, Takatsuki, Osaka, Japan. 4. Eli Lilly and Company, Bridgewater, NJ, U.S.A. 5. Eli Lilly Japan K.K., Kobe, Japan. 6. National Cancer Center Hospital East, Kashiwa, Japan.
Abstract
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. Copyright
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. Copyright
Authors: Linda T Vahdat; Rachel Layman; Denise A Yardley; William Gradishar; Mohamad A Salkeni; Anil Joy; Agustin A Garcia; Patrick Ward; James Khatcheressian; Joseph Sparano; Gladys Rodriguez; Shande Tang; Ling Gao; Rita P Dalal; John Kauh; Kathy Miller Journal: Oncologist Date: 2017-02-20
Authors: Joannes A A Reijers; Martijn J C Dane; Anton Jan van Zonneveld; Jacobus Burggraaf; Matthijs Moerland Journal: Eur J Drug Metab Pharmacokinet Date: 2018-02 Impact factor: 2.441