s-1-(combination) and amrubicin

Lung cancer is the leading cause of cancer-related death throughout the world including Japan. During the 1990s, new cytotoxic agents such as irinotecan, paclitaxel, docetaxel, vinorelbine, gemcitabine, and amrubicin showed impressive single-agent activity in patients with lung cancer. To date, clinical research has defined the current standard chemotherapy for advanced non-small cell lung cancer (NSCLC) as modern platinum-based doublets considered more efficacious than any single regimen and with no added benefit to triplet therapies. However, we have reached an efficacy plateau with these agents. Rearrangement of the drug combination or change of the drug doses and schedules will not result in significant further progress. New, less toxic agents that improve survival and quality of life are clearly needed. In the last three decades, we have gained a growing understanding of the molecular biologic changes and the complex series of cellular signals that allow cancer cells to manifest behavior. This provides an opportunity to develop novel therapies aimed at inhibiting some of these changes and signals. Targeted agents, primarily the epidermal growth factor receptor inhibitors, have led to a new era in the treatment of NSCLC. This paper will review the current status of cytotoxic agents and molecular targeted therapy in lung cancer potential useful in the treatment of the patients.

Topics: Anthracyclines; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Bevacizumab; Boronic Acids; Bortezomib; Camptothecin; Carcinoma, Non-Small-Cell Lung; Cetuximab; Clinical Trials as Topic; Deoxycytidine; Drug Combinations; Erlotinib Hydrochloride; Furans; Gefitinib; Gemcitabine; Glutamates; Guanine; Humans; Irinotecan; Lung Neoplasms; Oxonic Acid; Pemetrexed; Pyrazines; Pyridines; Quinazolines; Tegafur; Vinblastine; Vinorelbine

Both amrubicin (Am) and S-1 are effective against non-small-cell lung cancer (NSCLC), and preclinical studies have demonstrated that the effect of tegafur/uracil, the original compound of S-1, in combination with Am significantly inhibits tumor growth.. We conducted a phase I/II study of Am and S-1 against pretreated NSCLC without EGFR mutation. We fixed the dose of S-1 at 40 mg/m(2) on days 1-14 and escalated the Am dose in increments of 5 mg/m(2) from a starting dose of 30 mg/m(2)/day on days 1-3 and repeated the cycle every 4 weeks.. Twenty-six patients were registered. In phase I, at an Am dose of 35 mg/m(2)/day, three patients experienced grade 2 leukopenia during S-1 administration, and S-1 was withdrawn. Another patient developed grade 2 serum bilirubin in the first cycle. DLTs were observed in four of six patients at this dose level, and therefore, 30 mg/m(2)/day was set as the recommended dose for Am. Twenty patients received this recommended Am dose. Febrile neutropenia was observed in two patients, and one patient developed a grade 4 increase in serum creatinine. Grade 3 vomiting, infection, hypotension, and urinary retention were observed in one patient each, respectively. Other toxicities were mild, and there were no treatment-related deaths. Two patients showed a CR, three showed a PR, and the overall response rate was 25.0%. The median progression-free and the median survival times were 3.8 and 15.6 months, respectively, and the 1-year survival rate was 60%.. Am and S-1 every 4 weeks is an effective combination for pretreated NSCLC without EGFR mutation.

Topics: Adult; Aged; Anthracyclines; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Combinations; ErbB Receptors; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Mutation; Oxonic Acid; Survival Analysis; Tegafur