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Open Access 01-11-2018 | Original Article

Phase Ib study of irinotecan and ramucirumab for advanced gastric cancer previously treated with fluoropyrimidine with/without platinum and taxane

Authors: Hironaga Satake, Tamotsu Sagawa, Koshi Fujikawa, Yukimasa Hatachi, Hisateru Yasui, Masahito Kotaka, Takeshi Kato, Akihito Tsuji

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2018

Abstract

Purpose

Optimal salvage chemotherapy for patients with treated advanced/metastatic gastric cancer (AGC) is unknown. Irinotecan is commonly used in Japan. Ramucirumab, a human IgG-1 monoclonal antibody targeting the extracellular domain of VEGF receptor 2, is the first molecularly targeted agent proven to be effective in second-line therapy for AGC in combination with chemotherapy. We sought to determine the maximum tolerated dose (MTD) and recommended dose (RD) of ramucirumab plus irinotecan for AGC previously treated with fluoropyrimidine with/without platinum and taxane.

Methods

Patients received systemic chemotherapy with ramucirumab (8 mg/kg) and irinotecan on day 1, repeated every 2 weeks. A decrease in irinotecan dose was planned from start level 1 (irinotecan 150 mg/m²). This trial was registered with the University Hospital Medical Network (UMIN no. 000018606).

Results

Six patients were enrolled from August 2015 to September 2017. No dose-limiting toxicity (DLT) was observed, and the maximum tolerated dose (MTD) was not reached at level 1. Irinotecan 150 mg/m² in combination with ramucirumab 8 mg/kg was administered with acceptable toxicity, and all patients were treated at these doses. No treatment-related deaths were observed. Adverse events of Grade 3/4 were neutropenia (17%), anemia (17%) and hypertension (17%). Patients were evaluated using the RECIST criteria, and response rate and disease control rate were 17% and 83%, respectively.

Conclusions

Salvage chemotherapy with irinotecan plus ramucirumab was well-tolerated by patients previously treated for AGC. RD was defined as irinotecan 150 mg/m² in combination with ramucirumab 8 mg/kg.

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Title: Phase Ib study of irinotecan and ramucirumab for advanced gastric cancer previously treated with fluoropyrimidine with/without platinum and taxane
Authors: Hironaga Satake
Tamotsu Sagawa
Koshi Fujikawa
Yukimasa Hatachi
Hisateru Yasui
Masahito Kotaka
Takeshi Kato
Akihito Tsuji
Publication date: 01-11-2018
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 5/2018
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-018-3678-5

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