Capecitabine and oxaliplatin combined with bevacizumab are feasible for treating selected Japanese patients at least 75 years of age with metastatic colorectal cancer.
BACKGROUND
Although number of elderly patients with metastatic colorectal cancer (mCRC) is rapidly increasing, this population is often underrepresented in clinical trials. Recently, a phase II trial demonstrated that capecitabine and oxaliplatin (XELOX) combined with bevacizumab XELOX plus bevacizumab was effective and well tolerated by elderly patients with mCRC who reside in Western countries. The aim of this study was to evaluate the safety and efficacy of XELOX plus bevacizumab for Japanese patients aged ≥ 75 years with mCRC.


METHODS
This prospective, open-label phase II trial recruited patients aged ≥ 75 years with previously untreated mCRC between March 2010 and January 2012. Treatment consisted of 7.5 mg/kg of intravenous bevacizumab and 130 mg/m(2) of oxaliplatin on day 1 of each cycle combined with 2000 mg/m(2) of oral capecitabine per day on days 1-14 of each cycle. Treatment was repeated every 3 weeks until disease progression or termination of the study. The primary endpoint was progression-free survival; the secondary endpoints were toxicity, overall response rate, time-to-treatment failure, and overall survival.


RESULTS
Thirty-six patients (male 58%; median age 78 years; colon cancer 67%) met all eligibility criteria and received at least one course of the planned treatment. The median time-to-treatment failure was 7.0 months. Twelve patients (33.3%) experienced adverse effects (AEs) ≥ grade 3 and frequent AEs ≥ grade 3, including neutropenia (22.2%) and neuropathy (13.9%). Hypertension was the most frequent AE ≥ grade 3 associated with bevacizumab (11.1%). Low baseline creatinine clearance associated significantly with the incidence of AEs ≥ grade 3. Response and disease control rates were 55.6 and 91.7%, respectively. Median progression-free and overall survival times were 11.7 months (95% confidence interval, 8.0-13.4 months) and 22.9 months, respectively.


CONCLUSIONS
XELOX combined with bevacizumab was well tolerated by selected Japanese patients aged ≥ 75 years with mCRC patients, and controlled clinical trials are now required to determine the survival benefit.
Department of Surgery, Fukuiken Saiseikai Hospital, Fukui, Japan. Y-MUNEMOTO@fukui.saiseikai.or.jp.
Yoshinori
Y
Munemoto
Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan. m-kanda@med.nagoya-u.ac.jp.
Mitsuro
M
Kanda
Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan. k_ishi@saitama-med.ac.jp.
Keiichiro
K
Ishibashi
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan. thata@gesurg.med.osaka-u.ac.jp.
Taishi
T
Hata
Department of Human Health and Medical Sciences, Kochi Medical School, Kohasu, Japan. kobayasm@kochi-u.ac.jp.
Michiya
M
Kobayashi
Department of Surgery, Osaka Rosai Hospital, Sakai, Japan. j-hasegawa@orh.go.jp.
Junichi
J
Hasegawa
Department of Surgery, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Japan. fukunaga1404@hp.pref.hyogo.jp.
Mutsumi
M
Fukunaga
Surgical Division, Hakodate Goryoukaku Hospital, Hakodate, Japan. takagane@gobyou.com.
Akinori
A
Takagane
Department of Internal Medicine, Dongo Hospital, Yamatotakada, Nara, Japan. hxgcd792@yahoo.co.jp.
Toshio
T
Otsuji
Department of Surgery, Minoh City Hospital Gastrointestinal Research Center, Minoh, Osaka, Japan. hotymiyake@hotmail.com.
Yasuhiro
Y
Miyake
Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Japan. mnagase@nagoya-1st.jrc.or.jp.
Michitaka
M
Nagase
Director, Tokai Central Hospital, Gifu, Japan. sakamjun@med.nagoya-u.ac.jp.
Junichi
J
Sakamoto
Matsuoka Clinic, Kitakatsuragi, Nara, Japan. masa2722@mac.com.
Masaki
M
Matsuoka
Department of Biostatistics, School of Public Health, Tokyo University Graduate School of Medicine, Tokyo, Japan. oba@epistat.m.u-tokyo.ac.jp.|Interfaculty Initiative in Information Studies, Tokyo University, Tokyo, Japan. oba@epistat.m.u-tokyo.ac.jp.
Koji
K
Oba
Unit of Cancer Center, Aichi Medical University, Nagakute, Japan. hmishima@aichi-med-u.ac.jp.
Hideyuki
H
Mishima
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D044466:Asian People; D000068258:Bevacizumab / Q000008:administration & dosage* / Q000009:adverse effects; D000069287:Capecitabine / Q000008:administration & dosage* / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D000077150:Oxaliplatin; D011446:Prospective Studies; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000069287:Capecitabine