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Most current chemotherapy regimens for cancer consist of empirically designed combinations, based on efficacy and lack of overlapping toxicity. In the development of combinations, several aspects are often overlooked: (1) possible metabolic and biological interactions between drugs, (2) scheduling, and (3) different pharmacokinetic profiles. Antimetabolites(More)
PURPOSE To assess possible pharmacokinetic and pharmacodynamic interactions between gemcitabine and paclitaxel in a phase I/II study in non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS Eighteen patients with advanced NSCLC received the following in a 3-week schedule: gemcitabine 1,000 mg/m(2) (30 minutes, days 1 and 8) and paclitaxel 150(More)
PURPOSE To determine possible schedule dependent pharmacokinetic and pharmacodynamic interactions between gemcitabine (2',2'-difluorodeoxycytidine, dFdC) and cisplatin (cis-diammine-dichloroplatinum, CDDP) in patients with advanced stage solid tumors in a phase I trial. PATIENTS AND METHODS A total of 33 patients with advanced stage solid tumors were(More)
Gemcitabine (2'-2'-difluorodeoxycytidine; dFdC) is a deoxycytidine analogue which is effective against solid tumours, including lung cancer and ovarian cancer. dFdC requires phosphorylation by deoxycytidine kinase (dCK) for activation. In the human ovarian cancer cell line A2780 and its 30,000-fold dFdC-resistant variant AG6000 (P<0.001), we investigated(More)
Cisplatin and gemcitabine both have activity in solid tumors, such as non-small cell lung, ovarian, and head and neck cancers. These drugs have the desired features needed to obtain synergistic activity, different side effect profiles, and mechanisms of action. Cisplatin acts by forming DNA-DNA cross-links (both intrastrand and interstrand) and DNA-protein(More)
PURPOSE To evaluate the tolerability of four alternating cisplatin-gemcitabine schedules. A secondary aim was to evaluate the clinical efficacy of this combination. PATIENTS AND METHODS Forty-one patients with advanced solid tumors received alternating sequences with a 4- and 24-hour interval of cisplatin and gemcitabine. Gemcitabine 800 mg/m2 was(More)
We used the gemcitabine (dFdC) and cisplatin (cis-diamine dichloroplatinum CDDP) resistant murine NSCLC tumour Lewis Lung (LL) in C57/B16 mice to optimise scheduling of both drugs, since in previous in vivo studies no effective combination schedule of both compounds was found to overcome resistance to either drug. dFdC could not be combined at the(More)
Using a panel of patient cell lines with chromosomal breakpoints, we constructed a physical map for the short arm of human chromosome 11. We focused on 11p15, a chromosome band harboring at least 25 known genes and associated with the Beckwith-Wiedemann syndrome, several childhood tumors, and genomic imprinting. This underlines the need for a physical map(More)
Gemcitabine (2',2'-difluorodeoxycytidine) is an antineoplastic agent with clinical activity against ovarian carcinoma, small cell and non-small cell lung cancers, head and neck cancer, bladder cancer, breast cancer, and pancreatic cancer. Cisplatin (CDDP), etoposide (VP-16), and mitomycin C (MMC) are well-known anticancer agents that are also active against(More)
Both gemcitabine (2',2'-difluorodeoxycytidine, dFdC) and cisplatin (cis-diammine-dichloroplatinum) have significant anticancer activity against ovarian, head and neck, and non-small cell lung cancer (NSCLC). dFdC can be incorporated into DNA and RNA, and inhibit DNA repair, while cisplatin can form Pt-DNA adducts. We previously observed schedule-dependent(More)