krn-5500 and Carcinoma--Non-Small-Cell-Lung

Non-small cell lung cancer (NSCLC) is refractory to systemic chemotherapy, compared with small cell lung cancer. Until recently, only five drugs--cisplatin, vindesine, mitomycin, ifosfamide, and vinblastine--could produce overall response rates of 15% against NSCLC. However, recent efforts have contributed to the development of new drugs with activity against NSCLC, including irinotecan hydrochloride (CPT-11), paclitaxel, docetaxel, vinorelbine, and gemcitabine. Combination chemotherapy against NSCLC using these agents has demonstrated high response rates. In Japan, various combination chemotherapy and combined-modality regimens employing CPT-11 have been evaluated for their efficacy. Randomized controlled trials to establish new state-of-the-art treatments for NSCLC are ongoing.

Topics: Alkaloids; Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carbazoles; Carcinoma, Non-Small-Cell Lung; Clinical Trials as Topic; Docetaxel; Glucosides; Humans; Irinotecan; Japan; Lung Neoplasms; Mitomycin; Mitomycins; Neoplasms, Experimental; Paclitaxel; Purine Nucleosides; Staurosporine; Taxoids; Treatment Outcome; Vinblastine; Vinorelbine

KRN5500 is a new derivative of spicamycin produced by Streptomyces alanosinicus and is known to have a wide range of antitumor activities against human cancer cell lines. Because of its unique structure, this compound seems to have a different mode of action from other antitumor drugs and nonoverlapping toxicities. Therefore, KRN5500 is expected to be a suitable candidate for combination chemotherapy.. We investigated the effects of combinations of KRN5500 and other anticancer drugs on the growth of a human non-small-cell lung cancer cell line, PC14, using a revised three-dimensional model.. Synergism was observed when KRN5500 and cisplatin were combined at concentrations in the ranges 0.005 to 0.25 microg/ml and 0.025 to 0.25 microg/ml, respectively. In combination with carboplatin, an analog of cisplatin, and etoposide, a marked synergistic interaction was also found.. These results suggest the usefulness of combinations of KRN5500 with cisplatin, carboplatin or etoposide for chemotherapy for non-small-cell lung cancer.

Topics: Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Cell Division; Cisplatin; Dose-Response Relationship, Drug; Drug Synergism; Etoposide; Humans; Lung Neoplasms; Models, Biological; Models, Statistical; Purine Nucleosides; Tumor Cells, Cultured