l Clinical Investigation ADDITION OF CISPLATIN IMPROVES EFFICACY OF 1311-LABELED MONOCLONAL ANTIBODY 323/A3 IN EXPERIMENTAL

Purpose: This study was conducted to determine whether the cytotoxic agent cisplatin (CDDP), also known as sensitizer, can improve the efficacy of the ‘3’I-labeled monoclonal antibody (MAb) 323/A3 in the treatment of experimental human ovarian cancer. Methods and Materials: Nude mice bearing well-established subcutaneous FMa, OVCAR-3, or Ov.Pe xenografts were injected twice with a 2-week interval either with a bolus of CDDP, 1311-323/A3, or with a combination of both modalities. CDDP was injected at various timepoints when combined with 1311-323/A3. The efficacy of the treatment was expressed as the specific growth delay (SGD). The growth inhibitory effect of the combination was characterized to detect additivity or synergism, using the mean relative tumor volumes at 2,4, and 6 weeks after the last injection as endpoints. Results: The efficacy of j3’I-323/A3 was superior to that of the maximum tolerated dose (MTD) of CDDP (6 mgl kg)all three xenografts. The addition of CDDP to t3’I-323/A3 could increase the growth inhibition in the CDDP-responsive FMa and OVCAR3 xenografts, but not in Ov.Pe xenografts. Although this improved antitumor effect was additive rather than synergistic, the combination was more effective when compared with that of the MTD of each of the modalities alone. The time interval between the administration of a bolus injection of CDDP and 13%323/A3 had no effect on the extent of growth inhibition in OVCAR3 xenografts