Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immunoconjugate XMMCO-791/RTA consists of ricin A chain bound to a murine monoclonal antibody MoAb 791T. This monoclonal antibody (MoAb) binds to a glycoprotein of 72 kD, which is expressed on human colorectal carcinoma, ovarian carcinoma, and osteogenic sarcoma. XMMCO-791/RTA was tested in a Phase I trial with proposed dose escalation steps of 0.02, 0.04, 0.15, and 0.2 mg/kg per day. Twelve patients with metastatic colorectal carcinoma were treated at 0.02, 0.03, and 0.04 mg/kg per day dose levels administered over 1 hour on days 1-5. Study-related toxicities were hypotension (6 patients); greater than 10% weight gain (6 patients); peripheral edema (9 patients); fever (4 patients); confusion (3 patients); diarrhea (3 patients); proteinuria, as identified by dipstick (3 patients), greater than 0.6 mg/dl decrease in serum albumin (11 patients); greater than 25% decrease in oncotic pressure (10 patients), and a decrease in ionized calcium (8 patients). Six patients received a second course of treatment. HAMA levels developed in 9 patients and titers increased with number of courses administered. Decreased overall toxicity, in comparison to the first course, was noted, but one patient had an allergic-type response (hypotension, crushing chest pain, diaphoresis) after the test dose of the second course (HAMA level > 10,000 IgG). Life-threatening toxicity in the form of fluid shift, resulting in noncardiac pulmonary edema and third-spacing occurred after course 1 in 1 of 3 patients at the 0.04 mg/kg per day level. No further dose escalation was attempted and no antitumor activity was seen.
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PMID:Phase I study of monoclonal antibody-ricin A chain immunoconjugate Xomazyme-791 in patients with metastatic colon cancer. 762 72

Since MRD is the major cause for relapses of malignant diseases, strategies utilizing ITs to target tumor cells surviving conventional treatment have attracted scientific and clinical interest. Many different ITs against various blood-borne as well as solid malignancies have demonstrated specific potent anti-tumor effects in vitro and in animal models. Some of these have already undergone clinical phase I/II-trials. The dose-limiting toxicities of RTA ITs include manifestation of VLS presenting as decreased urinary sodium excretion, hypoalbuminemia, fatigue, hypotonia, myalgia, pulmonary edema, or rhabdomyolysis. Problems encountered clinically include the development of HAMA, HARA, and HACA and the selection of antigen-deficient malignant clones. Most clinical trials performed with ITs so far were conducted in heavily pretreated patients presenting with high tumor burdens. Thus, the responses observed with ITs in these trials are very encouraging and warrant further exploration.
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PMID:The emerging role of ricin A-chain immunotoxins in leukemia and lymphoma. 967 Jun 10