Protective Effects of Kampo Medicines and Baicalin against Intestinal Toxicity of a New Anticancer Camptothecin Derivative, Irinotecan Hydrochloride (CPT-11), in Rats
Kiyoshi Takasuna,Yoshio Kasai,Yutaka Kitano,Kazuhiko Mori,Reiko Kobayashi,Takehiro Hagiwara,Kohji Kakihata,Masaaki Hirohashi,Mamoru Nomura,Eiichi Nagai,Tetsuya Kamataki +10 more
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TLDR
Results suggest that the prophylactic use of Kampo medicines (TJ‐14 and TJ‐114) may be of value against CPT‐11‐induced intestinal toxicity.Abstract:
In clinical use, irinotecan hydrochloride (CPT-11; 7-ethyl-10-[4-(piperidino)-1-piperidino]carbonyloxycamptothecin), a novel antitumor agent, causes a relatively high incidence of severe forms of diarrhea We investigated whether baicalin, an inhibitor of beta-glucuronidase, which deconjugates the glucuronide of the active metabolite of CPT-11, SN-38 (7-ethyl-10-hydorxycamptothecin), and Japanese herbal medicines (Kampo medicines) which contain baicalin can ameliorate CPT-11-induced intestinal toxicity in rats CPT-11 (60 mg/kg iv once daily for 4 consecutive days) induced intestinal toxicity characterized by diarrhea, loss of body weight, anorexia and disruption of intestinal epithelium Treatment with baicalin (25 mg/kg po twice daily) or Kampo medicines (TJ-14 and TJ-114; 1 g/kg po twice daily) from the day before to 4 or 10 days after the start of CPT-11 administration resulted in significantly decreased weight loss, improved anorexia and delayed onset of diarrheal symptoms Histological examination revealed that Kampo medicine-treated animals had less damage to the intestinal epithelium and that damage was repaired more rapidly than in control rats These results suggest that the prophylactic use of Kampo medicines (TJ-14 and TJ-114) may be of value against CPT-11-induced intestinal toxicityread more
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References
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Plant Antitumor Agents. I. The Isolation and Structure of Camptothecin, a Novel Alkaloidal Leukemia and Tumor Inhibitor from Camptotheca acuminata1,2
Journal Article
Intracellular Roles of SN-38, a Metabolite of the Camptothecin Derivative CPT-11, in the Antitumor Effect of CPT-11
TL;DR: The results indicate that CPT-11 itself possesses a marginal antiproliferative effect but that SN-38 plays an essential role in the mechanism of action of C PT-11.
Journal ArticleDOI
A phase II study of CPT-11, a new derivative of camptothecin, for previously untreated non-small-cell lung cancer.
Masahiro Fukuoka,Hisanobu Niitani,Akira Suzuki,M Motomiya,K Hasegawa,Yutaka Nishiwaki,Takayuki Kuriyama,Yutaka Ariyoshi,S. Negoro,Noriyuki Masuda +9 more
TL;DR: CPT-11 is a very active agent for NSCLC with acceptable toxicities and further trials in combination with other agents for this disease are warranted.
Journal Article
Antitumor activity of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothec in, a novel water-soluble derivative of camptothecin, against murine tumors.
Takehiko Kunimoto,Kazuo Nitta,Tomiko Tanaka,Nobuaki Uehara,Hiroyasu Baba,Mieko Takeuchi,Teruo Yokokura,Siego Sawada,Tadashi Miyasaka,Masahiko Mutai +9 more
TL;DR: CPT-11 showed significant antitumor activity against a broad spectrum of experimental tumor models by i.p., i.v., or oral administration, giving the highest maximum increase in life span (ILS) and showing good activity over a wide dose range.
Journal ArticleDOI
Phase II study of CPT-11, a new camptothecin derivative, in metastatic colorectal cancer. CPT-11 Gastrointestinal Cancer Study Group.
Yasuhiro Shimada,Masahiro Yoshino,Akira Wakui,Isao Nakao,Koichi Futatsuki,Yuh Sakata,Mariko Kambe,Tetsuo Taguchi,Nobuya Ogawa +8 more
TL;DR: CPT-11 showed promising antitumor activity against metastatic colorectal cancer that was resistant to prior therapy and could be continued on an outpatient basis for patients without severe toxicity.