elsamicin-a and Lung-Neoplasms

Elsamitrucin (BMY-28090) a novel fermentation product has demonstrated pre-clinical anti-tumour activity against a number of cell lines. The dose limiting toxicity in phase I studies was a reversible increase in hepatic transaminase. This study was initiated to determine the activity of elsamitrucin in patients with previously untreated, bi-dimensionally measurable, cytologically or histologically proven, non-small cell lung cancer who were not curable by surgery. Elsamitrucin at a dose of 25 mg/m2 was administered intravenously over 5-10 min weekly for a minimum of 6 weeks. Seventeen patients were entered on study, 15 were evaluable for toxicity and 14 evaluable for response. No responses were documented in the 14 patients evaluable for response. Both hematological and non-hematological toxicities were mild to moderate in severity. The commonest being nausea, vomiting, lethargy and local skin reactions at the site of the infusion. These results indicate that elsamitrucin when given in this dose and schedule to patients with surgically incurable non-small cell lung cancer has no activity.

Topics: Aged; Aminoglycosides; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Drug Administration Schedule; Female; Humans; Injections, Intravenous; Lung Neoplasms; Male; Middle Aged

To test the antitumor activity of Elsamitrucin in metastatic cancer of the breast, colon and rectum, non-small cell lung and ovary.. Eligibility required histologically proven cancer. Patients with colorectal or non-small cell lung cancer could not have received prior chemotherapy. Patients were entered if WHO PS was < or = 2 and organ functions were normal. Treatment consisted of Elsamitrucin 25 mg/m2/week given as a 5-10 min infusion for at least 3-6 weekly doses.. One hundred and five patients entered the studies, 97 were eligible, 94 are evaluable for toxicity and 75 for response. Toxicity mainly consisted of mild nausea/vomiting, and less frequently reversible hepatotoxicity and malaise. No objective responses were seen.. Elsamitrucin at this dose and schedule is not an active drug in metastatic breast cancer, colorectal cancer, non-small cell lung cancer or ovarian cancer.

Topics: Adolescent; Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Ovarian Neoplasms

Elsamicin (EM) is a recently discovered antitumour agent that is structurally related to several other compounds displaying anticancer activities, including chartreusin (CT), chrysomycin V (CV) and M (CM), gilvocarcin V (GV) and ravidomycin (RM). The biochemical events resulting in cytotoxicity for most of these compounds have not been clearly elucidated. There is some evidence that GV and CT bind to DNA and that GV is photosensitive, causing DNA damage. Therefore, we investigated the effects of these chemicals on DNA in cells and on pBR322 plasmid DNA. Using alkaline elution techniques, we found that all these compounds induced, to a different extent, DNA breakage in the human lung adenocarcinoma A549 cell line. In addition, all either bound to or intercalated into DNA, as indicated by their ability to alter the electrophoretic migration of DNA in agarose gels. Using the P4 unknotting assay, EM, CT, CV, CM, GV and RM were found to be potent inhibitors of the catalytic activity of topoisomerase II (topo II). Their potencies were compared with the known topo II inhibitors teniposide (VM-26) and doxorubicin (DX). EM was the most potent, with an IC50 of 0.4 mumol/l followed in order by CV, GV, and CT. VM-26 was the least potent with an IC50 of 15 mumol/l. It was concluded from these results that EM, GV, CV, CM and CT are capable of inhibiting topo II and that EM is the most potent inhibitor of topo II yet discovered.

Topics: Adenocarcinoma; Aminoglycosides; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Benzopyrans; Cell Division; Coumarins; DNA Damage; DNA, Neoplasm; Glycosides; Humans; Lung Neoplasms; Topoisomerase II Inhibitors; Tumor Cells, Cultured