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01-08-2020 | Neutropenia | Original Article

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

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

Published in: Cancer Chemotherapy and Pharmacology | Issue 2/2020

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.

Available only for authorised users

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Title: Phase Ib study of FOLFOXIRI plus ramucirumab as first-line treatment for patients with metastatic colorectal cancer
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
Publication date: 01-08-2020
Publisher: Springer Berlin Heidelberg
Keywords: Neutropenia
Bevacizumab
Ramucirumab
Colorectal Cancer
Colorectal Cancer
Published in: Cancer Chemotherapy and Pharmacology / Issue 2/2020
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-020-04116-x

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