| Abstract: |
Cloretazine (VNP40101M), a new sulfonylhydrazine alkylating agent, has demonstrated broad-spectrum anti-tumor activity in preclinical studies. In this study, Cloretazine was evaluated both as a monotherapy and in combination with fludarabine in murine tumor and human tumor xenograft models. Cloretazine significantly inhibited the growth of subcutaneously implanted tumors, including B16F10 murine melanoma in C57BL/6 mice, and H460 human lung carcinoma and WiDr human colon carcinoma in athymic nude CD1 mice. The inhibition of tumor growth by Cloretazine was dose dependent, increasing from 42.2 to 87% as the dose escalated from 100 to 150 mg/kg. Cloretazine showed equivalent efficacy but lower toxicity compared to cyclophosphamide in these models. The combination therapy, consisting of a single dose of 10 mg/kg Cloretazine plus five doses of 70 mg/kg fludarabine, given every other day intraperitoneally, significantly increased the long-term survival of BDF1 mice bearing the L1210 murine leukemia. On Day 65 post-tumor implantation, the combination therapy yielded a 90% survival rate compared to 40% for Cloretazine alone and 0% for fludarabine alone. © 2007 Springer-Verlag. |
| Keywords: |
cancer survival; controlled study; survival analysis; leukemia; survival rate; unclassified drug; human cell; fludarabine; cancer combination chemotherapy; dose response; drug efficacy; nonhuman; mouse; animals; mice; drug inhibition; melanoma; antineoplastic combined chemotherapy protocols; animal experiment; animal model; weight loss; combination chemotherapy; cyclophosphamide; cancer cell culture; tumor xenograft; dose-response relationship, drug; drug screening assays, antitumor; xenograft model antitumor assays; cell line, tumor; mice, inbred c57bl; time factors; drug dose escalation; disease model; antiinfective agent; nude mouse; mice, nude; tumor burden; sulfonamides; antineoplastic agents, alkylating; carcinoma; melanoma, experimental; lung carcinoma; tumor growth; colon carcinoma; vidarabine; cancer transplantation; hydrazines; injections, intraperitoneal; anti-tumor effect; cloretazine; vnp40101m; leukemia l1210
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