Phase Ib study of FOLFOXIRI plus ramucirumab as first-line treatment for patients with metastatic colorectal cancer.

Abstract

PURPOSE:

Ramucirumab, an anti-vascular endothelial growth factor (VEGF) receptor2 monoclonal antibody, inhibits VEGF-A, VEGF-C, and VEGF-D binding and endothelial cell proliferation. We conducted a phase Ib study to determine the recommended phase II dose (RP2D) of fluorouracil, l-leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus ramucirumab.

METHODS:

This phase Ib study investigated three dose levels of FOLFOXIRI plus ramucirumab (three dose levels of irinotecan and fluorouracil with fixed dose of oxaliplatin 85 mg/m2 and ramucirumab 8 mg/kg on day 1, repeated every 2 weeks) in chemotherapy-naïve patients with metastatic colorectal cancer (mCRC). Dose-limiting toxicity (DLT) was assessed during the first cycle.

RESULTS:

A total of ten patients were enrolled. The first four patients received the treatment at dose level 0 (irinotecan 150 mg/m2 and fluorouracil 2400 mg/m2), and subsequent six patients were treated at dose level 1 (irinotecan 165 mg/m2 and fluorouracil 3200 mg/m2). No DLT was observed in the nine DLT-evaluable patients, which indicated that the RP2D was dose level 1. Grade 3 or worse adverse events included neutropenia (70%), hypertension (20%), and febrile neutropenia (10%). No treatment-related death was observed in any cycle. The overall response rate was 70%.

CONCLUSION:

The RP2D of FOLFOXIRI plus ramucirumab was determined to be 8 mg/kg of ramucirumab, 165 mg/m2 of irinotecan, 85 mg/m2 of oxaliplatin, 200 mg/m2 of l-leucovorin, and 3200 mg/m2 of fluorouracil.

TRIAL REGISTRATION NUMBER:

UMIN000023277.

• Authors: Yosuke Kito, Hironaga Satake, Hiroya Taniguchi, Takeshi Yamada, Yoshiki Horie, Taito Esaki, Tadamichi Denda, Hisateru Yasui, Naoki Izawa, Toshiki Masuishi, Toshikazu Moriwaki, Keita Mori, Kentaro Yamazaki
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 86 Issue 2 Pg. 277-284 (08 2020) ISSN: 1432-0843 [Electronic] Germany
• PMID: 32710148 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Oxaliplatin
• Irinotecan
• ramucirumab
• Leucovorin
• Fluorouracil

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Colorectal Neoplasms (drug therapy, pathology)
• Female
• Fluorouracil (administration & dosage)
• Follow-Up Studies
• Humans
• Irinotecan (administration & dosage)
• Leucovorin (administration & dosage)
• Liver Neoplasms (drug therapy, secondary)
• Lung Neoplasms (drug therapy, secondary)
• Lymphatic Metastasis
• Male
• Middle Aged
• Oxaliplatin (administration & dosage)
• Peritoneal Neoplasms (drug therapy, secondary)
• Prognosis
• Survival Rate
• Young Adult