Abstract
A rationale for postoperative adjuvant immunochemotherapy in patients with advanced neuroblastoma was searched through experiments used A/J mic bearing C-1300 murine neuroblastoma. 1. Cell kinetic of residual tumor cells after debulking surgery showed an increase of proliferative fraction from 18 to 42 hours after reduction surgery, while that of the bone marrow cells were seen from 24 to 96 hours later. 2. Administration of Na_2 ^<51>CrO_4 fluid intravenously into the operated tumor bearing mice demonstrated accelerated isotope intake in the residual tumor mass at any point postoperatively until day 5 than preoperative point, especialy at 6 hours and on day 3, which suggested enough blood flow and/or drug distribution to the residual tumor. 3. Early drug administration with the one fourth of murine LD_<50> on day 1 after reduction surgery, when cell kinetic of the residual tumor cells showed a biggest proliferative fraction, could not bring about a better chemotherapeutic effect than late administration on day 3. 4. Postoperative ip administration of small dose (75 or 15mg/kg) of cyclophosphamide (CPM) induced a remarkable delay of tumor growth and prolongation of the life span, which effect was largely abrogated on the immunoodifficient mice exposed to thymectomy and irradiation. 5. Transfer of the spleen cells from the tumor bearing operated mice shortened the latency time of tumor appearrence on the recipient mice, while transfer of the spleen cells from mice operated and administered with CPM did not influence the latency time of the recipients. Early postoperative administration of small dose of which is cytotoxic to suppressor cell fraction is seemingly promising. 6. Administration of CPM on day 3 after reduction surgery, when the proliferative fraction of bone marrow cells was biggest, caused a transient spleen reduction and the following rebound overshool swelling. Present data suggest the antitumor activity of CPM following reduction surgery of C-1300 neuroblastoma is mediated by both pharmacological and immunologic mechanisms.
