The toxicology of liposome-encapsulated amphotericin B in mice and its efficacy in the treatment and prophylaxis of systemic candidiasis in these animals were studied. The toxicology studies indicated that the maximal tolerated dose of free amphotericin B was 0.8 mg/kg of body weight and the 50% lethal dose (LD50) was reached at 1.2 mg/kg, while neither the maximal tolerated dose nor the LD50 for the liposomal amphotericin B was reached at a dose of 12 mg/kg. No abnormalities in blood chemistry or histology were observed in the animals injected with encapsulated amphotericin B, while the administration of free amphotericin B was associated with nephrocalcinosis and renal parenchymal edema. The encapsulated drug was as effective as the free drug when used in similar concentrations, while the animals treated with higher concentrations of liposomal amphotericin B (4 mg/kg) had a longer survival time. Thus, an improved therapeutic index resulted by encapsulating amphotericin B in liposomes.

Mab 14G2a has modest antitumor activity at the expense of significant toxicity. Dose-limiting neurologic sequelae may significantly limit phase II studies other than in pediatric patients with neuroblastoma.

Background. Radiolabeled CC49, a second generation high affinity monoclonal antibody (MoAb) reactive with tumor‐associated glycoprotein 72 (TAG72) has undergone previous Phase I testing in patients with colon cancer. Based on this report, the authors treated 15 refractory metastatic colon cancer patients with 131I‐CC49 to determine its overall toxicity and the response to therapy of patients treated with it. Methods. Patients received 75 mCi/m2 131I‐CC49 (20 mg MoAb) intravenously for a period of 30–60 minutes. Whole body retention was derived from the measured dose‐rate of I‐131 monitored daily at 1 m using an ion chamber. Two whole‐body and static‐gamma camera images were taken of patients on days 4 and 7 after the infusion. Results. Nonhematologic toxicity (Grade 1‐2) consisted of nausea (two patients), arthralgias (three patients), transient fever and chills (two patients), and transient blood pressure changes (two patients). At 4–5 weeks posttreatment, reversible Grade 3–4 thrombocytopenia was observed in 7 of 15 patients, and reversible Grade 3–4 granulocytopenia was observed in 6 of 15 patients. Twelve of 13 patients tested developed human anti‐mouse antibody (range, 161 to > 20,000 ng/ml) at 6–8 weeks postinfusion. Mean ± SD whole‐body half‐life (whole‐body retention) of 131I‐CC49 was 57.3 ± 13.4 hours. Tumors were seen in all patients. In two of three patients treated a second time, an increased whole body clearance rate correlated with elevated human anti‐mouse antibody, reduced uptake in tumor, and enhanced uptake in the thyroid. Estimated tumor doses ranged from 19–667 rads. Red marrow dose estimated from whole body retention ranged from 60 to 117 rads and correlated with decreases in platelet count. No objective tumor responses (i.e., partial or complete) were observed. Conclusions. Despite minimal toxicity and favorable tumor uptake, efficacy has been limited at this dose and schedule. Cancer 1994; 73:1057–66.

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These results suggest that 99mTc IMMU-4 scintigraphy is an important addition to the armamentarium available for diagnostic imaging and may help detect occult metastatic cancer missed by abdominal and pelvic CT in patients with rising CEA levels.