Disease relevance of Picoline

• The primary aim of this phase II trial was to assess the antitumour activity of ZD0473 in ovarian cancer patients who had failed initial platinum-based therapy [1].
• The main toxicity of ZD0473 was haematological (thrombocytopenia) and the most common non-haematological adverse event was nausea [2].
• ZD0473 treatment in lung cancer: an overview of the clinical trial results [3].
• Phase II trial of ZD0473 as second-line therapy in mesothelioma [2].
• CONCLUSION: ZD0473 has minor activity as a single agent in metastatic breast cancer [4].

High impact information on Picoline

• Exposure to ZD0473 prior to SN38 leads to a synergistic/additive schedule in LoVo/LoVo-5FUR cells, while SN38 --> ZD0473 schedule was only synergistic in parental cell lines [5].
• RESULTS: The pattern of response towards ZD0473, administered as single agent, was similar in all cases and independent of the 5FU-resistance phenotype (IC50 from 48.1 to 76.6 microM) and/or p53 status [5].
• PURPOSE: ZD0473 (AMD473) [cis-amminedichloro(2-methylpyridine) platinum(II)] is a novel platinum agent of proven activity in vitro against a variety of human tumor-derived cell lines even with intrinsic or acquired resistance to CDDP [5].
• The aim of this study is to provide the basis for a rational design of ZD0473-based combination in colon cancer [5].
• Notably, the simultaneous exposure to ZD0473 and paclitaxel for 96 h resulted in synergy (as defined by a median effect analysis) in all four cell lines (i.e. independent of cisplatin resistance and p53 status) [6].

Chemical compound and disease context of Picoline

• We examined the growth inhibitory effects of ZD0473 in human lung cancer cell lines resistant to cisplatin in vitro [7].
• In vitro effects of combinations of cis-amminedichloro (2-methylpyridine) platinum (II) (ZD0473) with other novel anticancer drugs on the growth of SBC-3, a human small cell lung cancer cell line [8].

Biological context of Picoline

• This Phase I dose-escalating study investigated the pharmacokinetics, tolerability and efficacy of ZD0473 in Japanese patients with solid, refractory tumours [9].
• Mechanisms of drug resistance to the platinum complex ZD0473 in ovarian cancer cell lines [10].
• The aim of this open-label phase I study was to determine the maximum tolerated dose (MTD), safety, and antitumour activity of ZD0473 followed by paclitaxel in patients with refractory solid malignancies [11].

Anatomical context of Picoline

• Sequencing studies with ZD0473 and paclitaxel revealed that, for three of the four cell lines, the combination of ZD0473 administered for 24 h prior to paclitaxel for 24 h conferred a greater growth inhibitory effect than the reverse sequential combination [6].

Gene context of Picoline

• Three open-label, non-comparative, multicentre Phase II trials have examined the efficacy and tolerability of ZD0473 as first-and second-line therapy in non-small-cell lung cancer (NSCLC) patients and second-line therapy in small-cell lung cancer (SCLC) patients [3].

Analytical, diagnostic and therapeutic context of Picoline

• The method provided adequate sensitivity for the analysis of plasma ultrafiltrate samples from a phase II study in which ZD0473 was administered to patients as an intravenous infusion at a dose of 150 mg/m2 [12].
• A comparison of the quantitative methods for the analysis of the platinum-containing anticancer drug [cis-[amminedichloro(2-methylpyridine)]platinum(II)] (ZD0473) by HPLC coupled to either a triple quadrupole mass spectrometer or an inductively coupled plasma mass spectrometer [13].
• The methods were then applied to the determination of plasma ultrafitrate concentrations of ZD0473 in dog plasma samples obtained following intravenous and oral administration at 0.5 and 6 mg/kg, respectively [13].
• The use of high performance liquid chromatography coupled with inductively coupled plasma mass spectrometry (HPLC-ICPMS) as means for the quantitative determination of ZD0473, a platinum anticancer drug, and its related biologically active "aqua" compounds in biofluid samples is described [13].
• The objectives were to evaluate the activity and tolerability of ZD0473 in patients with relapsed or progressive disease who had received one prior chemotherapy regimen [2].

References