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Background: To study the toxicity and pharmacokinetics of LU103793 (Cematodin®), a novel cytotoxic anticancer drug being an analogue of Dolastin 15 which was isolated originally fro

To determine the maximum tolerable dose (MTD), principal toxicity, and pharmacologic behaviour of Cemadotin-HCl, a novel antimitotic peptide.Cemadotin-HCl (10.0 to 27.5 mg/m2/day every three weeks) was administered as a 24-hour intravenous (i.v.) continuous infusion to patients with advanced cancer. Pharmacokinetic analyses were performed during the first treatment cycle. Blood samples were taken over 48 hours and analyzed by radioimmunoassay.Hypertension was the dose-limiting toxicity (DLT). This type of toxicity was observed at all dose levels, but grade 3 (CTC) was observed only at dose levels 20.0, 25.0 and 27.5 mg/m2. This effect was reversible but in three patients associated with signs of cardiac ischemia. Other significant toxic effects were neutropenia, asthenia, tumor pain and transient liver enzyme elevation. A linear pharmacokinetics was observed. The best curve fit was obtained with a two-compartment model with a terminal half-life of approximately 10 hours at each dose level, a volume of distribution at steady state of approximately 9 l/m2 and a total clearance of approximately 0.6 l/hour/m2. Neither partial nor complete responses were observed although minor tumor regressions were seen in a patient with carcinoma of unknown primary (CUP) and in another patient with liver metastases from a colon cancer.Hypertension was the dose-limiting toxicity of Cemadotin-HCl administered as a continuous 24-hour infusion. The recommended dose for further evaluation of its anticancer efficacy in disease-oriented phase II studies with this schedule is 15.0 mg/m2. The nature of the principal cardiovascular toxicity remains unclear. The observed toxicities appeared to be significant but manageable.

277 untreated multiple myeloma patients of stage I (n = 33), II (n = 106) and III (n = 138) entered the study. Patients of stage II presenting a progressive tumor (n = 64) initially or during observat

277 untreated multiple myeloma patients of stage 1 (n = 33), II (n = 106) and III (n = 138) entered the study. Patients of stage II presenting a progressive tumor (n = 64) initially or during observation (n = 14) were treated with MivP (remissions: 61%). 138 patients of stage III were randomized to receive MivP or VBAMDex treatment. 51% of MivP treated patients responded versus 70% of the VBAMDex group. 71 responders of stage II and III with stable disease were randomized on Ifn-alpha maintenance versus no maintenance treatment. The relapse rate in both groups was 50% after 7 months. 75% survival was greater than 36 months in stage II and 11 months in stage III patients.

136 untreated multiple myeloma patients of stage II and III were collected in the study. 37/51 stage II patients had progressive disease and were treated with melphalan and prednisone (MP). 85 patients were of stage III and randomized into MP and vincristine, BCNU, adriamycin, melphalan and dexamethasone (VBAMDex) treatment groups. 55% of MP treated patients responded versus 75% of the VBAMDex group. Since the study has been activated only 16 months ago, no difference in survival could be observed.

Previous investigations about the specificity of carp anti-idiotypic sera could be confirmed by comparison with corresponding antisera of guinea pigs. 3 carp antihuman myeloma-protein sera rendered as idiotypic specific after an appropriate absorption were tested in the passive hemagglutination inhibition test. They showed no difference to the parallel tested guinea pig antisera. It can be assumed that between fish antibodies and antibodies of mammals no functional difference exists in respect of antigen binding. On the other hand mammals exhibit a higher extent of structural antibody heterogeneity.