Tumor growth delay and cell survival after treatment with irradiation and vinblastine

The interaction of irradiation and vinblastine was investigated in a solid rat rhabdomyosarcoma. Growth delay of the tumor and cell survival by an in vitro assay were the endpoints measured. Vinblastine was administered at a dose of 1.5 mg/kg body weight at different time intervals before or after doses of 10 and 20 Gy of X-rays. Excess growth delay, i.e., the difference between observed growth delay for the combined radio-chemotherapy treatment and the sum of growth delays of individual treatments, was observed when vinblastine was administered at intervals of 1 to 12 days after or 2 to 8 days before the radiation doses.The clonogenic capacity of cells from tumors treated in vivo was messed using an in vitro survival assay. Cell survival data as a function of time after treatment with either vinblastine, a dose of 10 Gy of X-rays, or a dose of 10 Gy followed after 1 day by vinblastine were collected. The radiation treatment resulted in surviving fractions which remained constant up to 6 days after treatment. The effectiveness of vinblastine and of the combined treatments could be assessed 2 or 3 days after the drug application. The fractions of surviving cells determined after combined therapy were not significantly different from the fractions expected on the basis of simple multiplication of the fractions of surviving cells of individual treatments. This indicates that for a 1 day interval tumor growth delay observed after a dose of 10 Gy of X-rays followed by vinblastine correlates with a simple additional effect of the two individual treatments.