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.
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Authors | Li-mou Zheng, Zujin Li, Lanzhen Liu, Bai Louis Song, Ivan King |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 60
Issue 1
Pg. 45-51
(Jun 2007)
ISSN: 0344-5704 [Print] Germany |
PMID | 17256135
(Publication Type: Journal Article)
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Chemical References |
- Antineoplastic Agents, Alkylating
- Hydrazines
- Sulfonamides
- laromustine
- Cyclophosphamide
- Vidarabine
- fludarabine
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Topics |
- Animals
- Antineoplastic Agents, Alkylating
(administration & dosage, chemistry, therapeutic use)
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Cell Line, Tumor
- Cyclophosphamide
(administration & dosage)
- Dose-Response Relationship, Drug
- Drug Screening Assays, Antitumor
(methods)
- Humans
- Hydrazines
(administration & dosage, chemistry, therapeutic use)
- Injections, Intraperitoneal
- Leukemia L1210
(drug therapy, pathology)
- Melanoma, Experimental
(drug therapy, pathology)
- Mice
- Mice, Inbred C57BL
- Mice, Nude
- Sulfonamides
(administration & dosage, chemistry, therapeutic use)
- Survival Analysis
- Time Factors
- Tumor Burden
(drug effects)
- Vidarabine
(administration & dosage, analogs & derivatives)
- Weight Loss
- Xenograft Model Antitumor Assays
(methods)
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