HIGH-DOSE THERAPY WITH IODINE-131-LABELED MONOCLONAL-ANTIBODY CC49 INPATIENTS WITH GASTROINTESTINAL CANCERS - A PHASE-I TRIAL

Purpose: A phase I trial that evaluated for extrahematopoietic toxicit y was conducted with iodine-131 (I-131) labeled monoclonal antibody (M Ab) CC49. Correlative studies included pharmacokinetic and biodistribu tion analyses, estimates of absorbed radiation dose, and measurement o f human antimonoclonal antibodies (HAMA). Patients and Methods: After collection and cryopreservation of hematopoietic stem cells, 15 patien ts with gastrointestinal cancers were administered a tracer dose of I- 131-MAb CC49, Within 5 to 6 days, 14, patients (two to three per activ ity level) underwent a single treatment with I-131-MAb CC49 (50, 100, 150, 200, 250, and 300 mCi/m(2)). Biodistribution was determined using planar and single photon emission computer tomographic (SPECT) imagin g. Pharmacokinetic studies were performed by measuring radioactivity i n serial blood samples. In some patients, biopsies of metastases and r elated normal tissues were obtained for radioactivity measurements. Ra diation dosimetry estimates were calculated using available biodistrib ution, pharmacokinetic, and tissue biopsy data. Toxicity was evaluated using the National Cancer Institute (NCI) Common Toxicity Criteria. R esults: No dose-limiting extra hematopoietic toxicity was identified. Twelve patients experienced grade IV myelosuppression and met criteria for infusion of hematopoietic stem cells. Radioimmunolocalization was excellent, The T-1/2 for I-131-MAb CC49 after diagnostic and therapeu tic administration was 39.7 +/- 10.4 and 46.1 +/- 10.6 hours, respecti vely. The percent injected dose per killigram of tumor ranged from 0.2 to 2.1. Absorbed radiation dose in metastatic tumor sites ranged from 630 to 3300 cGy. Conclusion: Although extrahematopoietic dose-limitin g toxicity was neither observed or predicted, suboptimal absorbed dose estimates suggested that further escalation of I-131-MAb CC49 would n ot be useful. Future studies should focus on the use of radionuclides with high energy beta emissions, such as yttrium(90), and on strategie s to optimize access of antibody to target antigens. (C) 1997 by Ameri can Society of Clinical Oncology.