ADDITION OF CISPLATIN IMPROVES EFFICACY OF I-131-LABELED MONOCLONAL-ANTIBODY 323 A3 IN EXPERIMENTAL HUMAN OVARIAN-CANCER/

Purpose: This study was conducted to determine whether the cytotoxic a gent cisplatin (CDDP), also known as a radiosensitizer, can improve th e efficacy of the I-131-labeled monoclonal antibody (MAb) 323/A3 in th e treatment of experimental human ovarian cancer. Methods and Material s: 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, I-131-323/A3, or with a combination of both modalitie s, CDDP was injected at various timepoints when combined with I-131-32 3/A3, The efficacy of the treatment was expressed as the specific grow th delay (SGD). The growth inhibitory effect of the combination was ch aracterized to detect additivity or synergism, using the mean relative tumor volumes at 2, 4, and 6 weeks after the last injection as endpoi nts. Results: The efficacy of I-131-323/A3 was superior to that of the maximum tolerated dose (MTD) of CDDP (6 mg/kg) in all three xenograft s, The addition of CDDP to I-131-323/A3 could increase the growth inhi bition in the CDDP-responsive FMa and OVCAR-3 xenografts, but not in O v.Pe xenografts, Although this improved antitumor effect was additive rather than synergistic, the combination was more effective when compa red with that of the MTD of each of the modalities alone, The time int erval between the administration of a bolus injection of CDDP and I-13 1-323/A3 had no effect on the extent of growth inhibition in OVCAR-3 x enografts, Conclusion: The addition of CDDP to I-131-323/A3 resulted i n an additive inhibitory effect on the growth of CDDP-responsive xenog rafts, As the combination of radioimmunotherapy and CDDP was more effe ctive in the inhibition of the tumor growth when compared with that of the MTD of each of the modalities alone, this treatment may therefore be considered of use in patients with ovarian cancer responsive to CD DP. (C) 1997 Elsevier Science Inc.