Effective combination therapy of metastatic murine solid tumors with edatrexate and the vinca alkaloids, vinblastine, navelbine and vindesine Journal Article
| Authors: | Otter, G. M.; Sirotnak, F. M. |
| Article Title: | 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 tomor. 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≃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% longterm 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. © 1994 Springer-Verlag. |
| Keywords: | controlled study; nonhuman; mouse; animal; mice; antineoplastic combined chemotherapy protocols; animal experiment; combination chemotherapy; antineoplastic activity; tumor cells, cultured; mice, inbred c57bl; vinblastine; fibrosarcoma; breast carcinoma; neoplasms, experimental; vindesine; vinca alkaloid; navelbine; aminopterin; lewis carcinoma; intraperitoneal drug administration; mice, inbred dba; edatrexate; subcutaneous drug administration; female; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s. |
| Journal Title: | Cancer Chemotherapy and Pharmacology |
| Volume: | 33 |
| Issue: | 4 |
| ISSN: | 0344-5704 |
| Publisher: | Springer |
| Date Published: | 1994-07-01 |
| Start Page: | 286 |
| End Page: | 290 |
| Language: | English |
| DOI: | 10.1007/bf00685901 |
| PROVIDER: | scopus |
| PUBMED: | 8281620 |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- Source: Scopus |
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