Enhancement of antitumor activity of 5'-deoxy-5-fluorouridine (Furtulon) by taxane in human gastric cancer xenografts.
5'-deoxy-5-fluorouridine (5'-DFUR, Furtulon) is activated to 5-fluorouracil (5-FU) by thymidine phosphorylase (dThdPase) highly expressed in many types of tumors. In previous studies, we demonstrated that taxanes (paclitaxel or docetaxel) up-regulated the tumor levels of dThdPase and enhanced the efficacy of 5'-DFUR in human colon and mammary xenograft models. In the present study, combination therapy of 5'-DFUR with taxanes in human gastric cancer xenograft models also showed, at the least, additive anti-tumor activity without significant augmentation of toxicity. Furthermore, paclitaxel up-regulated dThdPase expression in the tumor tissues as confirmed with ELISA and immunohistochemistry. These results suggest taxanes would potentiate the efficacy of 5'-DFUR by up-regulating the tumor levels of dThdPase in gastric xenograft models. Clinical trials of 5'-DFUR in combination with taxane against gastric cancer are warranted.
Sawada
Noriaki
N
Product Research Department, Chugai Pharmaceutical Co., Ltd., 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan. sawadanra@chugai-pharm.co.jp
Nose
Taeko
T
Ishikawa
Tohru
T
Yutaka
Tanaka
T
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D045744:Cell Line, Tumor; D005467:Floxuridine / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage; D013939:Thymidine Phosphorylase / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D001952:Bridged-Ring Compounds; D043823:Taxoids; D005467:Floxuridine; C080625:taxane; D013939:Thymidine Phosphorylase; C025034:doxifluridine