Correlation between primary chemo- and radiation sensitivity in a panel of highly malignant human soft tissue sarcoma xenografts.

Abstract

Sensitivity to radiation and sensitivity to cytotoxic drugs have been proposed to be independent properties of tumour cells. However, very few clinical or experimental studies have tested this hypothesis. Therefore, we evaluated the response to ionizing radiation and to four cytotoxic drugs in a panel of 12 human soft tissue sarcoma cell lines using the xenograft system. NMRI-nu/nu nude mice with subcutaneous tumours received at a tumour volume of 120-200 mm3 either single dose, single agent chemotherapy with 350 mg/kg ifosfamide, 200 mg/kg dacarbazine, 10 mg/kg doxorubicin, 6.6 mg/kg cisplatin, or 24 Gy local tumour irradiation under acutely hypoxic conditions from a cobalt-60 source. Tumour response to radiotherapy and chemotherapy was measured as specific growth delay (SGD). A significant correlation was found between SGD after radiotherapy and SGD after decarbazine (P < 0.001) and doxorubicin (P = 0.05), whereas no correlation could be demonstrated for cisplatin. For ifosfamide, the correlation reached borderline significance. The maximal response to any of the four tested chemotherapeutic drugs correlated very well with the response to radiotherapy (P < 0.001). The results suggest that radiation sensitivity and chemosensitivity are not independent properties of soft tissue sarcoma cell lines.