Correlation of cell kinetic and clinical response to chemotherapy in disseminated neuroblastoma

Mitotic and labeling indices of bone marrow tumor cells were determined from patients with disseminated neuroblastoma. Although pretreatment values were variable, the median indices indicated that only a small proportion of tumor cells were proliferating. The pretreatment indices could not be correlated with presenting clinical features or with the response to chemotherapy. Studies were repeated after 7 daily doses of cyclophosphamide (150 mg/sq m) and serially after Adriamycin (35 mg/sq m) given on Day 8. Changes in the mitotic and labeling indices during the first course of therapy could be directly correlated with the clinical response as evaluated after 4 months of induction chemotherapy. In all patients who attained a complete or partial remission, an increase in these indices was observed after 7 days of cyclophosphamide. If this increase was associated with an observed kinetic effect of Adriamycin in the G1, S, and G2 phases of the cell cycle, a complete remission was attained. If, following Adriamycin, kinetic evidence of an effect was not present in all three phases of the cell cycle, only partial remission was attained. No clinical response to therapy was observed in those patients in whom the mitotic index and labeling index did not increase after 7 days of cyclophosphamide.