THE EFFECT OF COMBINED NICOTINAMIDE AND CARBOGEN TREATMENTS IN HUMAN TUMOR XENOGRAFTS - OXYGENATION AND TUMOR-CONTROL STUDIES

Background and purpose: This was an investigation to study the effect of giving carbogen and nicotinamide (CON) on pO(2) and the radiation r esponse of human xenografted tumours. Materials and Methods: The human xenografts were two sarcomas (ENE2 and ES3) and a glioblastoma (HTZ17 ). Nicotinamide (500 mg/kg, i.p.) was administered 60 min before pO(2) measurements and irradiation, while carbogen was given for 5 min befo re and during these treatments. Tumour pO(2), was measured with an Epp endorf electrode and radiation response was assessed by local tumour c ontrol following irradiation with 10 daily fractions. Results: All thr ee xenografts were found to be poorly oxygenated (about 80% of all pO( 2) values were less than or equal to 2.5 mmHg). CON treatment improved the oxygenation status in all three tumours such that 65, 52 and 71% of the pO(2) values were less than or equal to 2.5 mmHg in ENE2, ES3 a nd HTZ17, respectively. However, only in ES3 was this decrease signifi cant. The TCD50 doses for all tumours were around 52-54 Gy. No signifi cant improvement was seen with CON in ENE2 (TCD50 = 48 Gy) and HTZ17 ( TCD50 = 56 Gy), but for the ES3 xenograft a significant decrease to 42 Gy was found. Conclusions: The three tumours used in this study appea red to show the same level of hypoxia as measured both by pO(2) and ra diation response. However, only one tumour showed a significant improv ement after CON treatment, suggesting that not all hypoxic human tumou rs might benefit from this type of therapy. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.