Effect of Methylprednisolone on the Cell Kinetic Response of C3H/HeJ Mammary Tumors to Cyclophosphamide and Adriamycin1

The effect of methylprednisolone (MP) on the cell kinetic response to Cyclophosphamide (CP) and Adriamycin (ADR) in C3H/HeJ spontaneous mammary tumors and hematopoietic tissue was investigated. The [3H]deoxythymidine labeling in dex, the primer-dependent DNA polymerase labeling index (an estimate of tumor growth fraction), and the mitotic index were determined at various intervals after treatment. Treatment con sisted of CP (200 mg/kg) on Day 0 plus ADR (2 mg/kg) on Day 1 with or without MP every 12 hr for 9 doses beginning on Day 2. In tumors treated with CP and ADR alone, changes in the kinetic parameters suggested proliferative recovery be tween Days 3 and 4 which coincided with bone marrow recov ery. In tumors treated with CP, ADR, and MP, although the timing of the hematopoietic recovery was not affected by MP, the overshoot of the [3H]deoxythymidine labeling index on Days 3 and 4 was abolished. Proliferative recovery in the tumor was delayed until after cessation of MP treatments. Cell kinetic changes in the tumor after CP, ADR, and MP were used to design effective sequential chemotherapy which obviated the hematopoietic toxicity associated with sequential therapy de signed from cell kinetic changes after CP and ADR alone.