Usefulness of alternate-day administration of S-1 and leucovorin in a xenograft mouse model of colorectal cancer: a shorter drug-free interval leads to more efficient antitumor effects
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| 024 | 7 | 0 | |a 10.1007/s10147-014-0699-x |2 doi |
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| 245 | 0 | 0 | |a Usefulness of alternate-day administration of S-1 and leucovorin in a xenograft mouse model of colorectal cancer: a shorter drug-free interval leads to more efficient antitumor effects |h [Elektronische Daten] |c [Toshihiro Komura, Koh Miura, Tetsuhiko Shirasaka, Shinobu Ohnuma, Miki Shimada, Taiki Kajiwara, Fumiyoshi Fujishima, Alex Philchenkov, Kei Nakagawa, Katsuyoshi Kudoh, Sho Haneda, Masahide Toshima, Atsushi Kohyama, Hiroaki Musha, Takeshi Naitoh, Chikashi Shibata, Michiaki Unno] |
| 520 | 3 | |a Background: A clinical trial of S-1 with leucovorin (S-1/LV) in metastatic colorectal cancer (CRC) patients demonstrated promising efficacy; however, the gastrointestinal toxicities were so severe that it has not been applied in the clinical setting. On the other hand, alternate-day administration of S-1 has been proposed to attenuate the adverse events without reducing its anticancer activity. Our present study was conducted to confirm the feasibility of alternate-day administration of S-1/LV in in vivo xenograft tumor models. Methods: Mice were treated with S-1/LV in a daily group (2weeks of administration followed by 2weeks of withdrawal) or an alternate-day group (administration on alternate days for 4weeks), then the mice were killed and the xenograft tumors were resected. We compared body weight changes, condition of feces, mucosal injury and myelosuppression and assessed adverse reactions, tumor volume, tumor growth inhibition (TGI) and expression of Ki67, TUNEL, cIAP2 and XIAP to evaluate the antitumor activity and tumor apoptosis. Results: Severe weight loss, diarrhea, mucosal injury and myelosuppression were observed only in the daily group; however, some myelosuppression was also observed in the alternate-day group. The TGI in the alternate-day group was better than in the daily group, possibly resulting from apoptosis due to the suppression of cIAP2 but not XIAP. Conclusion: Our findings suggest that alternate-day administration of S-1/LV for CRC treatment can achieve high antitumor activity without severe adverse reactions, and we propose that clinical trials with this regimen should be conducted in CRC patients. | |
| 540 | |a Japan Society of Clinical Oncology, 2014 | ||
| 690 | 7 | |a S-1 |2 nationallicence | |
| 690 | 7 | |a Leucovorin |2 nationallicence | |
| 690 | 7 | |a Alternate-day administration |2 nationallicence | |
| 690 | 7 | |a Colorectal cancer |2 nationallicence | |
| 690 | 7 | |a In vivo mouse model |2 nationallicence | |
| 690 | 7 | |a S-1/LV : S-1 and leucovorin |2 nationallicence | |
| 690 | 7 | |a CRC : Colorectal cancer |2 nationallicence | |
| 690 | 7 | |a TGI : Tumor growth inhibition |2 nationallicence | |
| 690 | 7 | |a 5-FU : 5-Fluorouracil |2 nationallicence | |
| 690 | 7 | |a GI : Gastrointestinal |2 nationallicence | |
| 690 | 7 | |a FT : Tegafur |2 nationallicence | |
| 690 | 7 | |a CDHP : 5-Chloro-2,4-dihydroxypyridine |2 nationallicence | |
| 690 | 7 | |a Oxo : Potassium oxonate |2 nationallicence | |
| 690 | 7 | |a LV : Leucovorin |2 nationallicence | |
| 690 | 7 | |a HPMC : Hydroxypropyl methyl cellulose |2 nationallicence | |
| 690 | 7 | |a BWC : Body weight change |2 nationallicence | |
| 690 | 7 | |a TUNEL : Terminal deoxynucleotidyl transferase-mediated nick end labeling |2 nationallicence | |
| 690 | 7 | |a SD : Standard deviation of mean |2 nationallicence | |
| 690 | 7 | |a FdUMP : 5-Fluorodeoxyuridine-5′-monophosphate |2 nationallicence | |
| 690 | 7 | |a 5,10-CH2-THF : 5,10-Methylene-tetrahydrofolate |2 nationallicence | |
| 690 | 7 | |a TS : Thymidylate synthase |2 nationallicence | |
| 690 | 7 | |a IAP : Inhibitor of apoptosis protein |2 nationallicence | |
| 690 | 7 | |a NLRP3 : NOD-like receptor family, pyrin domain containing 3 |2 nationallicence | |
| 700 | 1 | |a Komura |D Toshihiro |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | |
| 700 | 1 | |a Miura |D Koh |u Department of Surgery, Miyagi Cancer Center, 47-1 Nodayama, Shiote, Medeshima, 981-1293, Natori, Miyagi, Japan |4 aut | |
| 700 | 1 | |a Shirasaka |D Tetsuhiko |u Kitasato Institute for Life Science, Kitasato University, 5-9-1 Shirokane, Minato-ku, 108-8641, Tokyo, Japan |4 aut | |
| 700 | 1 | |a Ohnuma |D Shinobu |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | |
| 700 | 1 | |a Shimada |D Miki |u Pharmaceutical Science, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | |
| 700 | 1 | |a Kajiwara |D Taiki |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | |
| 700 | 1 | |a Fujishima |D Fumiyoshi |u Department of Pathology, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | |
| 700 | 1 | |a Philchenkov |D Alex |u R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, 45 Vasylkivska Street, 03022, Kyiv, Ukraine |4 aut | |
| 700 | 1 | |a Nakagawa |D Kei |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | |
| 700 | 1 | |a Kudoh |D Katsuyoshi |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | |
| 700 | 1 | |a Haneda |D Sho |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | |
| 700 | 1 | |a Toshima |D Masahide |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | |
| 700 | 1 | |a Kohyama |D Atsushi |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | |
| 700 | 1 | |a Musha |D Hiroaki |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | |
| 700 | 1 | |a Naitoh |D Takeshi |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | |
| 700 | 1 | |a Shibata |D Chikashi |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | |
| 700 | 1 | |a Unno |D Michiaki |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | |
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| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Komura |D Toshihiro |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Miura |D Koh |u Department of Surgery, Miyagi Cancer Center, 47-1 Nodayama, Shiote, Medeshima, 981-1293, Natori, Miyagi, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Shirasaka |D Tetsuhiko |u Kitasato Institute for Life Science, Kitasato University, 5-9-1 Shirokane, Minato-ku, 108-8641, Tokyo, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Ohnuma |D Shinobu |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Shimada |D Miki |u Pharmaceutical Science, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | ||
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| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Fujishima |D Fumiyoshi |u Department of Pathology, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Philchenkov |D Alex |u R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, 45 Vasylkivska Street, 03022, Kyiv, Ukraine |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Nakagawa |D Kei |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Kudoh |D Katsuyoshi |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Haneda |D Sho |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Toshima |D Masahide |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Kohyama |D Atsushi |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Musha |D Hiroaki |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Naitoh |D Takeshi |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Shibata |D Chikashi |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Unno |D Michiaki |u Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Miyagi, Japan |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t International Journal of Clinical Oncology |d Springer Japan |g 20/1(2015-02-01), 117-125 |x 1341-9625 |q 20:1<117 |1 2015 |2 20 |o 10147 | ||