nc-190 and Neoplasms

Irinotecan hydrochloride (CPT-11), topotecan, sobuzoxane, NC-190, and IST-622 are unique topoisomerase inhibitors and are investigational in Japan. CPT-11 is a water-soluble, semisynthetic derivative of camtothecin. CPT-11 shows its anticancer activity by inhibiting topoisomerase I activity, now a target of anticancer agents with major interest. Recent clinical trials reveal that CPT-11 is very effective in the treatment of cancer including lung cancer, cervical cancer, ovary cancer, stomach cancer, colon cancer, and non-Hodgkin's lymphoma. Major dose limiting toxicities are leukopenia and diarrhea, and are dose related. Topotecan is an another semisynthetic derivative of camtothecin and is also topoisomerase I inhibitor. Topotecan has undergone phase I clinical evaluations in USA, europe, and recently in Japan. DLF are leukopenia and neutropenia. Topotecan is more hydrophilic than its parent compound and shows lesser protein binding. Renal excretion appears to be the major route of elimination. Sobuzoxane (MST-16) is a unique derivative of dioxopiperazine, an inhibitor of topoisomerase II. In phase II studies, definite anticancer effects are observed in patients with non-Hodgkin's lymphoma and adult T-cell leukemia/lymphoma. Responses are seen even in pretreated cases. Leukopenia is also dose-limiting. Non-hematologic toxicities are mild and include alopecia and G.I. toxicities. NC-190 is a novel benzophenazine derivative with excellent antitumor activities against murine tumors. NC-190 also inhibits topoisomerase II. Now the drug is an early clinical phase II studies in Japan. Toxicities include bone marrow suppression, transient mild to moderate liver enzyme elevation, alopecia and mild G.I. toxicities. Tumor responses are occasionally encountered. IST-622 is a semisynthetic derivative of chartreusin. The drug is an inhibitor of topoisomerase II (and I in high concentration). IST-622 shows excellent, broad anticancer activity against murine tumors. The drug is well absorbed from small intestine. IST-622 is now in phase I clinical trial in Japan.

Topics: Animals; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Benzopyrans; Camptothecin; Diketopiperazines; Glycosides; Humans; Irinotecan; Neoplasms; Phenazines; Piperazines; Razoxane; Topotecan

A method of assessing chemosensitivity of tissue utilizing tissue fluorescence and image analysis was implemented to provide a rapid and quantitative means of assessing the effect of drugs on tissue metabolic activity and proliferative capacity. The fluorescent microscopic image captured by a silicon-intensified target (low-light-detecting) camera and linked to an image- processing unit was measured for fluorescent brightness and tumor image area. An established rodent model served to characterize the system's ability to measure serially the tumor's metabolic activity and growth. Further studies on fresh human tumors were conducted with a novel topoisomerase II inhibitor, NC-190. Tumor image area and fluorescent brightness were measured 24 h pretreatment, 48 h posttreatment, and 48 h post-drug removal. Fifty-five percent (28/51) of fresh human tumors showed sensitivity to 48-h exposure to 10, 30, or 100 microM NC-190. The potential benefit of this technique is the ability to predict the response of tumors to chemotherapeutic agents as a laboratory tool for preclinical drug evaluation and clinically prior to the commencement of therapy.

Topics: 1,2-Dimethylhydrazine; Adenocarcinoma; Animals; Antineoplastic Agents; Biopsy; Cell Survival; Colonic Neoplasms; Drug Screening Assays, Antitumor; Fluoresceins; Fluorescent Dyes; Humans; Image Processing, Computer-Assisted; Jejunal Neoplasms; Microscopy, Fluorescence; Neoplasms; Phenazines; Rats; Topoisomerase II Inhibitors