Pharmacokinetic studies in the chemotherapy of neuroblastoma using the C1300 murine system

The transplantable C1300 murine neuroblastoma has been characterized biochemically and an in vivo model for the screening of new therapeutic approaches to the treatment of neuroblastoma developed. Subcutaneous inoculation of A/J mice with 10)6) C1300 cells results in predictable tumor growth and animal death in 25 +/- 4 days. Tumor growth is Gompertzian, correlates with increases in tumor RNA and DNA content and with the rate of tumor DNA synthesis as measured by [3H] thymidine incorporation. The model proposed is based on the degree to which various therapeutic options are able to inhibit tumor DNA synthesis, and these observations have been confirmed autoradiographically. A single course of either cyclophosphamide (25, 50, 100 or 200 mg/kg), BCNU (2, 7.5, 15, or 30 mg/kg) or cytosine arabinoside (15, 30, 60, 90 mg/kg) resulted in dose-related inhibition of tumor DNA synthesis. The maximum decline in DNA synthesis that was produced by the highest dose of each agent was by 81%, 77% and 68% of untreated tumor values respectively. Adriamycin, however, even at lethal levels (10 mg/kg), did not elicit significant inhibition of tumor DNA synthesis. Radiotherapy (200 R, 500 R or 1000 R) also produced graded inhibition of tumor DNA synthesis. This model is potentially useful for the preclinical screening of therapuetic options in the treatment of neuroblastoma. Thus, single agent therapy, combination chemotherapy and combined radiotherapy and chemotherapy may be rapidly evaluated for possible clinical use.