The effect of combined nicotinamide and carbogen treatments in human tumour xenografts: oxygenation and tumour control studies.
OBJECTIVE
This was an investigation to study the effect of giving carbogen and nicotinamide (CON) on pO2 and the radiation response of human xenografted tumours.


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 PO2 measurements and irradiation, while carbogen was given for 5 min before and during these treatments. Tumour pO2 was measured with an Eppendorf electrode and radiation response was assessed by local tumour control following irradiation with 10 daily fractions.


RESULTS
All three xenografts were found to be poorly oxygenated (about 80% of all pO2 values were < or =2.5 mmHg). CON treatment improved the oxygenation status in all three tumours such that 65, 52 and 71% of the pO2 values were < or =2.5 mmHg in ENE2, ES3 and HTZ17, respectively. However, only in ES3 was this decrease significant. The TCD50 doses for all tumours were around 52-54 Gy. No significant 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 appeared to show the same level of hypoxia as measured both by pO2 and radiation response. However, only one tumour showed a significant improvement after CON treatment, suggesting that not all hypoxic human tumours might benefit from this type of therapy.
Department of Radiotherapy, Strahlenklinik im Universitätsklinikum Essen, Germany.
G
G
Stüben
M
M
Stuschke
K
K
Knühmann
M R
MR
Horsman
H
H
Sack
D000280:Administration, Inhalation; D000818:Animals; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000627:therapeutic use*; D015687:Cell Hypoxia / Q000187:drug effects; D004338:Drug Combinations; D005909:Glioblastoma / Q000378:metabolism / Q000532:radiotherapy*; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D018319:Neurofibrosarcoma / Q000378:metabolism / Q000532:radiotherapy*; D009536:Niacinamide / Q000008:administration & dosage / Q000627:therapeutic use*; D010100:Oxygen / Q000008:administration & dosage / Q000627:therapeutic use*; D010101:Oxygen Consumption / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D012509:Sarcoma / Q000378:metabolism / Q000532:radiotherapy*; D012513:Sarcoma, Experimental / Q000378:metabolism / Q000532:radiotherapy; D012878:Skin Neoplasms / Q000378:metabolism / Q000532:radiotherapy; D014183:Transplantation, Heterologous
D004338:Drug Combinations; D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; D009536:Niacinamide; C011700:carbogen; D010100:Oxygen