title: Combination phase I study of nedaplatin and gemcitabine for advanced non-small-cell lung cancer.
abstract: To establish the toxicities and maximum tolerated dose (MTD) of nedaplatin with gemcitabine, and to observe their antitumour activity, we conducted a combination phase I study in advanced non-small-cell lung cancer (NSCLC). Patients received nedaplatin (60-100 mg m(-2) given intravenously over 90 min) on day 1, and gemcitabine (800-1000 mg m(-2) given intravenously over 30 min) on days 1, 8, every 3 weeks. In total, 20 patients with locally advanced or metastatic NSCLC who received no prior chemotherapy or one previous chemotherapy regimen were enrolled. The most frequent toxicities were neutropenia and thrombocytopenia; nonhaematological toxicities were generally mild. Three out of six patients experienced dose-limiting toxicities (neutropenia, thrombocytopenia and delayed anaemia) at dose level 4, 100 mg m(-2) nedaplatin with 1000 mg m(-2) gemcitabine, which was regarded as the MTD. There were three partial responses, for an overall response rate of 16.7%. The median survival time and 1-year survival rate were 9.1 months and 34.1%, respectively. This combination is well tolerated and active for advanced NSCLC. The recommended dose is 80 mg m(-2) nedaplatin with 1000 mg m(-2) gemcitabine. This combination chemotherapy warrants a phase II study and further evaluation in prospective randomised trials with cisplatin- or carboplatin-based combinations as first-line chemotherapy for advanced NSCLC.
authors.affiliation: Department of Medical Oncology, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kurata
authors.forename: K
authors.initials: K
authors.lastname: Tamura
authors.forename: N
authors.initials: N
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Nogami
authors.forename: T
authors.initials: T
authors.lastname: Satoh
authors.forename: H
authors.initials: H
authors.lastname: Kaneda
authors.forename: K
authors.initials: K
authors.lastname: Nakagawa
authors.forename: M
authors.initials: M
authors.lastname: Fukuoka
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D013921:Thrombocytopenia / Q000139:chemically induced; D000093542:Gemcitabine
chemical_list: D009944:Organoplatinum Compounds; D003841:Deoxycytidine; C053989:nedaplatin; D000093542:Gemcitabine