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Effective combination therapy of metastatic murine solid tumors with edatrexate and the vinca alkaloids, vinblastine, navelbine and vindesine.

Abstract：

:Studies are described in which a new folate analogue, edatrexate (EDX), in combination with the vinca alkaloids, vinblastine (VBL), navelbine (NVB) or vindesine (DVA) was evaluated against E0771 mammary adenocarcinoma, T241 fibrosarcoma and the Lewis lung tumor. Each of the four agents when given individually to animals 3 days after transplant of these tumors resulted in increases in survival of 53-143%. The relative effectiveness of these agents was (in increasing order) VBL, NVB congruent to DVA, EDX, with no long-term survivors obtained with any. Combination therapy with EDX and vinca alkaloids required dosage attenuation but was still markedly more effective. Treatment of E0771 and T241 tumors with EDX and either NVB or DVA increased survival 3- to 4-fold compared with therapy with individual agents and yielded 40-70% long-term survivors, while EDX with VBL increased survival 2- to 3-fold and yielded 20-40% long-term survivors. Simultaneous or sequential (EDX given 24 h before vinca alkaloid) administration of combined therapy was equally effective. Sequential administration of these agents at the same doses in the reverse order was highly toxic and required further dosage attenuation which compromised efficacy. Effects of these combinations against the Lewis Lung tumor were not as pronounced and were somewhat schedule-dependent. Simultaneous administration of EDX with VBL, NVB or DVA increased survival 2- to 3-fold over that obtained with single agents alone and yielded 10-40% long-term survivors, while sequential administration increased survival < 2-fold over that obtained with single agents and yielded 0-20% long-term survivors. These results suggest that combined therapy with these agents in patients may have appreciable utility and provide a basis for further clinical trials.

journal_name

Cancer Chemother Pharmacol

journal_title

Cancer chemotherapy and pharmacology

authors

Otter GM,Sirotnak FM

doi

10.1007/BF00685901

subject

Has Abstract

pub_date

1994-01-01 00:00:00

pages

286-90

issue

eissn

0344-5704

issn

1432-0843

journal_volume

pub_type

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Effective combination therapy of metastatic murine solid tumors with edatrexate and the vinca alkaloids, vinblastine, navelbine and vindesine.