Vincristine-methotrexate combination chemotherapy and the influence of weight loss on experimental tumour growth.

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 leads to 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.