Naloxone as an adjuvant in chemotherapy of an experimental tumor.

Abstract

The antitumor effect of DAB (L-2,4 diaminobuturic acid) has been demonstrated in a previous study. Severe side-effects (especially weight loss and severe neurological symptoms) accompanying DAB treatment have raised the theory that DAB, through a direct effect on the hypothalamus, might cause a diabetes insipidus-like condition, which in turn would activate endogenous opiate systems. This study has verified this state of dehydration and hemoconcentration in a group of 41 mice treated daily with 0.5 ml 0,1 M DAB solution IP. A rise in the serum albumin concentration to 28.8 g/l (SD 2.04) was demonstrated, as against 23.7 g/l (SD 2.3) in a control series. Furthermore, to prevent the neurological side-effects, an adjuvant treatment with an opiate antagonist (Nalone; naloxone) was tried in a group of 19 tumor-bearing mice receiving DAB. This group was compared with a group of 19 tumor-bearing mice receiving DAB only. The mortality rate was significantly reduced in the group receiving Nalone together with DAB (2 dead out of 19) compared with the other group (9 dead out of 19). The tumor weight reduction was about the same in the two groups, 40.5% and 46%, respectively. Combined treatment with DAB and Nalone seems to indicate a possible way of reducing the severe side-effects hitherto accompanying DAB alone, making this unique amino acid a potentially useful antitumor agent.