Tohoku J. Exp. Med., 2018 May, 245(1)

Intermittent Withdrawal of Oxaliplatin for Alleviating Neurotoxicity during Oxaliplatin-Based Chemotherapy for Japanese Patients with Inoperable or Metastatic Colorectal Cancer: A Phase 2 Multicenter Study

SHUNSUKE KATO,¹ HIROO IMAI,¹ MAKIO GAMOH,² TAKENORI TAKAHATA,³ HISATSUGU OHORI,² KATSUHIRO YASUDA,⁴ TOMOHITO NIITANI,⁵ YASUKO MURAKAWA,⁶ KENJI AMAGAI,⁷ HIDEKI ISOBE,⁸ YOSHIAKI SHINDO,⁹ MICHIO KUROKI,¹⁰ YASUHIRO SAKAMOTO,² HIDEKI SHIMODAIRA,¹ TAKASHI YOSHIOKA¹¹ and CHIKASHI ISHIOKA¹

¹Department of Medical Oncology, Tohoku University Hospital, Sendai, Miyagi, Japan
²Department of Medical Oncology, Osaki Citizen Hospital, Osaki, Miyagi, Japan
³Department of Medical Oncology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
⁴Department of Medical Oncology, Sendai Medical Center, Sendai, Miyagi, Japan
⁵Department of Medical Oncology, South Miyagi Medical Center, Shibata-gun, Miyagi, Japan
⁶Department of Cancer Chemotherapy, Miyagi Cancer Center, Natori, Miyagi, Japan
⁷Division of Gastroenterology and G.I. Oncology, Ibaraki Prefectural Central Hospital, Kasama, Ibaraki, Japan
⁸Department of Surgery, Yamagata University Hospital, Yamagata, Yamagata, Japan
⁹Department of Gastroenterological Surgery, Nakadori General Hospital, Akita, Akita, Japan
¹⁰Department of Gastroenterology, Yamagata City Hospital Saiseikan, Yamagata, Yamagata, Japan
¹¹Department of Clinical Oncology, Faculty of Medicine, Yamagata University, Yamagata, Yamagata, Japan

Oxaliplatin-based chemotherapy is a well-established regimen for patients with inoperable and metastatic colorectal cancer. However, one of the major limitations of oxaliplatin-based chemotherapy is sensory neuropathy. It was previously reported that introduction of intermittent oxaliplatin treatment to an oxaliplatin-based regimen has a significant benefit on efficacy or safety. Here, we prospectively assessed whether efficacy and safety of first-line chemotherapy for advanced colorectal cancer are achieved by introduction of withdrawal of oxaliplatin treatment for a certain period (intermittent oxaliplatin treatment). The primary endpoint of the present study is to assess the progression free survival time on patients treated with chemotherapy (mFOLFOX6 (levofolinate, 5-fluorouracil and oxaliplatin combination therapy) plus bevacizumab or CapeOX (oxaliplatin and capecitabine combination therapy) plus bevacizumab) with intermittent oxaliplatin treatment. Bevacizumab is a humanized anti-vascular endothelial growth factor antibody. Median progression-free survival by the mFOLFOX6 plus bevacizumab with intermittent oxaliplatin treatment or the CapeOX plus bevacizumab with intermittent oxaliplatin treatment were 10.6 months (95% confidential interval [CI], 8.3-13.4 months) or 8.0 months (95% CI, 4.2-16.8 months), respectively. Overall response rate by the mFOLFOX6 plus bevacizumab with intermittent oxaliplatin treatment or CapeOX plus bevacizumab with intermittent oxaliplatin treatment was 55.1% or 42.1%, respectively. Grade 3 or 4 neuropathy was observed in 4.1% or 10.5% of patients treated with mFOLFOX6 plus bevacizumab with intermittent oxaliplatin treatment or CapeOX plus bevacizumab with intermittent oxaliplatin treatment, respectively. Introduction of intermittent oxaliplatin treatment has improved severe neuropathy in mFOLFOX6 plus bevacizumab regimen without reducing treatment efficacy.