caa a22 4500 465789838 CHVBK 20180323112020.0 cr unu---uuuuu 170327e19900301xx s 000 0 eng 10.1007/BF00171983 doi (NATIONALLICENCE)springer-10.1007/BF00171983 Phase I trial of a 5-day course of carbetimer [Elektronische Daten] [Steven Grunberg, Elizabeth Ehler, Robert Francis Jr., Malcolm Mitchell] Summary: Carbetimer (carboxyimamidate) is a low molecular weight derivative of ethylene/maleic anhydride polymer. This compound has demonstrated antitumor activity against several animal models with a daily x 5 schedule appearing most effective. A phase I clinical study of the daily x 5 schedule repeated every 28 days was therefore performed. Forty-one evaluable patients received 66 evaluable cycles of Carbetimer at daily doses ranging from 100-11000 mg/m2. Hypercalcemia was the dose limiting toxicity with both patients at the 11000 mg/m2 daily dose level and one patient who received 6 cycles of drug at the 4200 mg/m2 dose level developing severe hypercalcemia not explained by the underlying malignancy. Mild nausea, concentration and rate dependent arm pain at the site of infusion, proteinuria, and coagulopathy were also seen. Calcium balance studies revealed hypercalciuria, suggesting increased mobilization of calcium rather than renal retention. In vitro coagulation studies revealed concentration dependent prolongation of the partial thromboplastin time and thrombin time. No complete or partial responses were seen. However mixed response or biochemical response (reduction in serum lactic dehydrogenase) were seen in 5 patients with melanoma or renal cancer. Due to unacceptable toxicity at the 11000 mg/m2 daily dose level, Carbetimer 8500 mg/m2 is the recommended dose for a 5-day treatment schedule every 28 days. Special attention should be directed toward possible activity against melanoma and renal cancer. Kluwer Academic Publishers, 1990 carbetimer nationallicence polymer nationallicence phase I nationallicence Grunberg Steven Division of Medical Oncology, University of Southern California, Comprehensive Cancer Center, 2025 Zonal Avenue, 90033, Los Angeles, CA, USA aut Ehler Elizabeth Division of Medical Oncology, University of Southern California, Comprehensive Cancer Center, 2025 Zonal Avenue, 90033, Los Angeles, CA, USA aut Francis Jr. Robert The Divisions of Medical Hematology, University of Southern California Comprehensive Cancer Center and Los Angeles County-University of Southern California Medical Center, 90033, Los Angeles, California, USA aut Mitchell Malcolm Division of Medical Oncology, University of Southern California, Comprehensive Cancer Center, 2025 Zonal Avenue, 90033, Los Angeles, CA, USA aut Investigational New Drugs Kluwer Academic Publishers 8(1990-03-01), S41-S49 0167-6997 8<S41 1990 8 10637 https://doi.org/10.1007/BF00171983 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00171983 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Grunberg Steven Division of Medical Oncology, University of Southern California, Comprehensive Cancer Center, 2025 Zonal Avenue, 90033, Los Angeles, CA, USA aut NATIONALLICENCE 700 1- Ehler Elizabeth Division of Medical Oncology, University of Southern California, Comprehensive Cancer Center, 2025 Zonal Avenue, 90033, Los Angeles, CA, USA aut NATIONALLICENCE 700 1- Francis Jr Robert The Divisions of Medical Hematology, University of Southern California Comprehensive Cancer Center and Los Angeles County-University of Southern California Medical Center, 90033, Los Angeles, California, USA aut NATIONALLICENCE 700 1- Mitchell Malcolm Division of Medical Oncology, University of Southern California, Comprehensive Cancer Center, 2025 Zonal Avenue, 90033, Los Angeles, CA, USA aut NATIONALLICENCE 773 0- Investigational New Drugs Kluwer Academic Publishers 8(1990-03-01), S41-S49 0167-6997 8<S41 1990 8 10637 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer