Summary
According to pharmacokinetic reports, vincristine administration should precede methotrexate therapy. Our sequential treatment of L1210 leukaemic mice, in which vincristine was administered before methotrexate therapy, was as effective as treatment with the two drugs given simultaneously. In solid tumour experiments we were unable to show any increase in the antitumour effect of methotrexate when vincristine was injected before methotrexate administration. Consequently, we advocate the re-evaluation of the practice of vincristine →methotrexate therapy as used in many clinical protocols for the treatment of patients with osteosarcoma.
Pretreatment with vincristine resulted in methotrexate-induced weight loss and sometimes in toxic death of the mice. Since the growth of tumours can be modified by regulation of the caloric intake of the host, this aspect was investigated in more detail. The effect of starvation, which was comparable to the effect of drug-induced weight loss, had a retarding effect on tumour growth. The growth rates of smaller tumour volumes were less severely affected than were those of large tumour masses.
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Bender, R. A., Drake, J. C., Fisher, R. I., Chabner, B. A.: Letter to the Editor. N. Engl. J. Med. 292, 432 (1975)
Bender, R. A., Nichols, A. P., Norton, L., Simon, R. M.: Lack of therapeutic synergism between vincristine and methotrexate in L1210 murine leukemia in vivo. Cancer Treat. Rep. 62, 997 (1978)
Brennan, M. F.: Uncomplicated starvation versus cancer cachexia. Cancer Res. 37, 2359 (1977)
Chello, P. L., Dorick, D. M., Sirotnak, F. M.: Different effects of vincristine on methotrexate uptake by L1210 cells and mouse intestinal epithelia in vitro and in vivo. Proc. Am. Assoc. Cancer Res. 18, 121 (1977)
Chello, P. L., Sirotnak, F. M., Dorick, D. M., Moccio, D. M., Gura, J.: Schedule-dependent synergism of methotrexate and vincristine against L1210 leukemia. Proc. Am. Assoc. Cancer Res. 19, 113 (1978)
EORTC and SIOP: Controlled clinical trial on adjuvant therapy in the treatment of osteosarcoma of the limbs (03 protocol). 1978
Fusner, J. E., Ramu, A., Gratwohl, A.: Effect of vincristine (VCR) on methotrexate (MTX) pharmacokinetics in vivo. Proc. Am. Assoc. Cancer Res. 19, 235 (1978)
Goldman, D., Gupta, V., White, J. C., Loftfield, S.: Exchangeable intracellular methotrexate levels in the presence and absence of vincristine at extracellular drug concentrations relevant to those achieved in high dose methotrexate-folinic acid “rescue” protocols. Cancer Res. 36, 276 (1976)
Jaffé, N., Frei, E., III, Watts, H., Traggis, D.: High-dose methotrexate in ostogenic sarcoma: a 5-year experience. Cancer Treat. Rep. 62, 259 (1978)
Livingston, R. B., Carter, S. K.: Single agents in cancer chemotherapy. New York: If1/Plenum 1970
Mulder, J. H., Van Putten, L. M.: Lack of vincristine/cyclophosphamide potentiation in different experimental tumour lines. Eur. J. Cancer (in press, 1979)
Mulder, J. H., Smink, T., Van Putten, L. M.: Schedule-dependent effectiveness of CCNU and 5-Fluorouracil in experimental chemotherapy. Eur. J. Cancer 13, 1123 (1977)
Mulder, J. H., Edelstein, M. B., Lelieveld, P., Van Putten, L. M.: Synergism and schedule dependent cytotoxicity of cyclophosphamide and CCNU in experimental cancer chemotherapy. Eur. J. Cancer 14, 537 (1978)
National Cancer Institute: Compilation of clinical protocol summaries. Bethesda: U.S. Department of Health, Education and Welfare 1977
Sandor, R. S.: Brief communication: Effects of fasting on growth and glycolysis on the Ehrlich ascites tumor. J. Natl. Cancer Inst. 56, 427 (1976)
Strogand, J. J., Braunschweiger, P. G., Pollice, A. A., Schiffer, L. M.: Cell kinetic alterations in murine mammary tumours following fasting and refeeding. Eur. J. Cancer 15, 281 (1979)
Warren, R. D., Nichols, A. P., Bender, R. A.: The effect of vincristine on methotrexate uptake and inhibition of DNA synthesis by human lymphoblastoid cells. Cancer Res. 37, 2993 (1977)
Zager, R. F., Frisby, S. A., Oliverio, V. T.: The effects of antibiotics and cancer chemotherapeutic agents on the cellular transport and antitumor activity of methotrexate in L1210 murine leukemia. Cancer Res. 33, 1670 (1973)
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Mulder, J.H., van Putten, L.M. Vincristine-methotrexate combination chemotherapy and the influence of weight loss on experimental tumour growth. Cancer Chemother. Pharmacol. 3, 111–116 (1979). https://doi.org/10.1007/BF00254981
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DOI: https://doi.org/10.1007/BF00254981