Biomedical subjects

M G Muto

Publications and source records attributed to M G Muto.

41 records · Page 3Linked to original sources

PubMed1992

Intraperitoneal radioimmunotherapy of refractory ovarian carcinoma utilizing iodine-131-labeled monoclonal antibody OC125.

Refractory epithelial ovarian cancer is generally confined to the peritoneal cavity and is thus amenable to intraperitoneal (ip) therapy. Radiolabeled monoclonal antibodies raised to tumor-associated antigens offer the promise of selective tumor irradiation while reducing toxicity to normal tissues. We have conducted a phase I therapeutic trial to examine the feasibility of ip radioimmunotherapy utilizing escalating doses of 131I-labeled OC125 F(ab')2. Twenty-nine patients were each treated with a single dose of radiolabeled antibody. Twenty-eight patients were evaluable for dose-related toxicity. The toxicities most frequently observed were hematologic and gastrointestinal. Hematologic toxicity was noted in 5/14 (36%) patients receiving 18-87 mCi and in 12/14 (71%) receiving 100-144 mCi (P = 0.018). The median white blood cell nadir of 2-3K/microliters (range, 1.4-3.5K/microliters occurred at a median of 4.5 weeks and the median platelet nadir of 41K/microliters (range, 20-78K/microliters) at a median of 6.5 weeks. Mild gastrointestinal toxicity was observed in 4/14 patients (28%) at doses less than 100 mCi whereas at doses greater than or equal to 100 mCi, 11/14 (79%) patients developed nausea, vomiting, or chronic ileus (P = 0.021). This toxicity occurred most frequently in patients with protracted urinary 131I excretion. We conclude that 131I-labeled OC125 can be safely administered ip. Hematologic and gastrointestinal toxicity is predictable and related to the dose and rate of clearance of isotope.

Animals↗

PubMed1991

Gestational trophoblastic disease of the fallopian tube.

Tubal gestational trophoblastic disease (GTD) was diagnosed in 16 (0.8%) of 2,100 women with GTD managed at the New England Trophoblastic Disease Center. Tubal partial mole, complete mole and choriocarcinoma were present in 5, 5 and 6 patients, respectively. Patients with tubal GTD were not clinically distinguishable from those with traditional tubal pregnancies. While only one patient with tubal mole developed metastases, four patients with tubal choriocarcinoma presented with metastases. All the patients achieved complete, sustained remission.

Adolescent↗

PubMed1990

Human anti-murine antibody responses in ovarian cancer patients undergoing radioimmunotherapy with the murine monoclonal antibody OC-125.

Human anti-murine antibody (HAMA) responses were monitored in 23 patients with recurrent or persistent epithelial ovarian carcinoma undergoing single-dose intraperitoneal radioimmunotherapy (RIT) with the murine monoclonal antibody OC-125. Sera of patients receiving escalating doses of OC-125 F(ab')2 (10-70 mg) radiolabeled with 18 to 141 mCi of iodine-131 were assayed for HAMA by a protein A-based radioimmunoassay. Overall, 70% of patients (16/23) developed HAMA within 10 to 46 days (median = 29) postinfusion, with peak values (23 +/- 6 to 325 +/- 10 micrograms/ml) at 32 to 102 days (median = 38). HAMA was undetectable prior to infusion in all cases and persisted up to 76 weeks. Of patients receiving a dose of 123 mCi or less, 80% (16/20) developed HAMA, whereas in the 140-mCi group, none of the three patients had detectable levels. Two patients in the 140-mCi group demonstrated dose-limiting bone marrow toxicity (severe thrombocytopenia and neutropenia). It is concluded that a single intraperitoneal dose of monoclonal antibody leads to a high incidence of HAMA production. The results also suggest that the likelihood of HAMA formation in patients who either had undergone recent chemotherapy or had received the highest dose of the radioimmunoconjugate is reduced. These observations may be of significance in designing multiple-dose therapy trials as HAMA has been demonstrated to decrease antibody-to-tumor binding and may potentially increase renal, hepatic, and hematologic toxicity associated with radioimmunotherapy.

Adult↗

PubMed1989

Influence of human antimurine antibody on CA 125 levels in patients with ovarian cancer undergoing radioimmunotherapy or immunoscintigraphy with murine monoclonal antibody OC 125.

Human antimurine antibody responses interfere with CA 125 antigen determinations by crosslinking the murine antiovarian carcinoma monoclonal antibody OC 125 with the second murine radiolabeled antibody used in the CA 125 radioimmunoassay. Serial CA 125 levels in 22 patients with epithelial ovarian carcinoma undergoing either radioimmunotherapy or radioimmunoscintigraphy with iodine 131-labeled F(ab')2 fragments of OC 125 were followed up for up to 96 weeks after infusion. Fourteen radioimmunoscintigraphy patients received 131I-labeled monoclonal antibody by the intraperitoneal (n = 5) or intravenous (n = 9) route: 10 of 14 had sera drawn at appropriate time points for human antimurine antibody detection; 8 of 10 had 1.3- to 363-fold increases in CA 125; 4 of 8 had detectable human antimurine antibody (18.5 to 22 and 575 to 36 micrograms/ml). Eight radioimmunotherapy patients received 131I-labeled monoclonal antibody by the intraperitoneal route: 8 of 8 displayed an apparent 4.8- to 3725-fold increase in CA 125 levels within 7 to 42 days after monoclonal antibody infusion; 6 of 8 had detectable human antimurine antibody (13 to 4 and 319 to 31 micrograms/ml). Adsorption of immunoglobulin G resulted in a 21% to 98% reduction in CA 125 antigen levels in 4 of 4 patients tested. In patients with demonstrable human antimurine antibody, CA 125 antigen levels obtained by the clinical CA 125 radioimmunoassay are spuriously elevated.

Adsorption↗

PubMed1989

Intraperitoneal radiolabeled OC 125 in patients with advanced ovarian cancer.

Twenty patients with recurrent or persistent epithelial ovarian cancer failing conventional therapies were treated with a single intraperitoneal injection of iodine-131-labeled OC 125 monoclonal antibody. Rare acute side effects were nausea and mild diarrhea. At doses up to 120 mCi of iodine-131, median white blood cell and platelet count nadirs were 3.6k/microliters and 187k/microliters, respectively. Two patients acquired thyroid toxicities despite thyroid blockage with "cold" iodine. One patient had transient TSH elevation while remaining clinically euthyroid, and 1 patient developed activation of a thyroid nodule and clinical hyperthyroidism. Dose-limiting toxicity has not yet been observed. Twelve of 20 patients are alive 3 to 17 months following therapy. Tumor progression was noted in the majority of patients, although 3 patients had documented decreases in tumor burden of short duration. We conclude that, at the doses examined, iodine-131 OC 125 can be safely administered intraperitoneally.

Adenocarcinoma↗