Addition of cisplatin improves efficacy of 131I-labeled monoclonal antibody 323/A3 in experimental human ovarian cancer.
This study was conducted to determine whether the cytotoxic agent cisplatin (CDDP), also known as a radiosensitizer, can improve the efficacy of the 131I-labeled monoclonal antibody (MAb) 323/A3 in the treatment of experimental human ovarian cancer.


METHODS
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, 131I-323/A3, or with a combination of both modalities. CDDP was injected at various timepoints when combined with 131I-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 131I-323/A3 was superior to that of the maximum tolerated dose (MTD) of CDDP (6 mg/kg) in all three xenografts. The addition of CDDP to 131I-323/A3 could increase the growth inhibition in the CDDP-responsive FMa and OVCAR-3 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 131I-323/A3 had no effect on the extent of growth inhibition in OVCAR-3 xenografts.


CONCLUSIONS
The addition of CDDP to 131I-323/A3 resulted in an additive inhibitory effect on the growth of CDDP-responsive xenografts. As the combination of radioimmunotherapy and CDDP was more effective 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 CDDP.
Kievit
E
E
Department of Medical Oncology, Academic Hospital Vrije Universiteit, Amsterdam, The Netherlands.
Pinedo
H M
HM
Schlüper
H M
HM
Boven
E
E
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000628:therapy*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D002945:Cisplatin