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Chemotherapy of human colorectal tumor xenografts in athymic mice with clinically active drugs: 5-fluorouracil and 1-3-bis-(-2-chloroethyl)-1-nitrosourea (BCNU). Comparison with doxorubicin derivatives: 4'deoxydoxorubicin and 4'-O-methyldoxorubicin.

Abstract：

:The effects of single-agent therapy with two clinically useful drugs, 5-fluorouracil (5-FU) and 1-3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) against nine human colorectal tumors (rectum T 157 and T 348, lung metastasis T 84, lymph-node metastasis T 245, colon, T 183, T 219, T 347, T 362 and T 380) transplanted and passed serially in thymic (nude) mice were studied. In addition, chemosensitivity of the tumors to 5-FU and BCNU was compared with the chemosensitivity of the tumors to two new doxorubicin analogues, 4'-deoxydoxorubicin and 4'-0-methyldoxorubicin. BALB/c nude mice were treated intravenously on a weekly basis for 3-4 weeks, starting when the tumor volume became relatively large (advanced stage of tumor treatment). All the tumors showed a 90-100% take rate and stable growth. In these experiments, 77% (5/9) of the colorectal tumors were biologically sensitive to the treatment with 5-FU but the percentage of statistically significant sensitive tumors was 22%, which is in good agreement with the clinical data reported in the literature (21%). In patients, BCNU has been reported to give up to 13% response. In contrast, we have found a 33% statistically significant response rate in our panel of colorectal tumors. The difference could be related to the higher tolerance of nude mice to certain drugs, including BCNU. The results suggest that the two new doxorubicin derivatives, 4'-deoxydoxorubicin and 4'-0-methyldoxorubicin, should be more active in the patient than both of the clinically used drugs, 5-FU and BCNU. Furthermore, there is a good correlation between the results obtained in the experimental system (human tumor/nude mouse) and in human patients with the active drugs, 5-FU and BCNU.

journal_name

Int J Cancer

journal_title

International journal of cancer

authors

Giuliani FC,Zirvi KA,Kaplan NO,Goldin A

doi

10.1002/ijc.2910270103

subject

Has Abstract

pub_date

1981-01-15 00:00:00

pages

5-13

issue

eissn

0020-7136

issn

1097-0215

journal_volume

pub_type

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Chemotherapy of human colorectal tumor xenografts in athymic mice with clinically active drugs: 5-fluorouracil and 1-3-bis-(-2-chloroethyl)-1-nitrosourea (BCNU). Comparison with doxorubicin derivatives: 4'deoxydoxorubicin and 4'-O-methyldoxorubicin.