Erlotinib failed to show an improvement in PFS or OS compared with docetaxel in an EGFR-unselected patient population.

Irinotecan with carboplatin is effective for advanced NSCLC and safe.

The pharmacokinetics of (glycolato-0,0')-diammine platinum (II) (254-S; NSC 375101D), one of the new platinum analogues, was examined in a phase I study of this drug and compared with that of cisplatin and carboplatin. All drugs were given in short-term (30-min) i.v. drip infusions; the doses of 254-S, cisplatin, and carboplatin were 100, 80, and 450 mg/m2, respectively. Platinum concentrations in whole plasma, plasma ultrafiltrate, and urine were determined by atomic absorption spectrometry. After the infusion, the plasma concentration of total platinum for the three agents decayed biphasically. Ultrafilterable platinum in plasma decreased in a biexponential mode after infusions of 254-S and carboplatin, whereas the free platinum of cisplatin showed a monoexponential disappearance. The peak plasma concentrations and AUC for free platinum were 5.31 micrograms/ml and 959 micrograms/min per ml for 254-S, 3.09 micrograms/ml and 208 micrograms/min per ml for cisplatin, and 19.90 micrograms/ml and 3446 micrograms/min per ml for carboplatin, respectively. The mean ratio of plasma ultrafilterable platinum to total platinum were calculated, and the results showed that the protein-binding abilities of 254-S and carboplatin were almost identical. More than 50% of the 254-S was excreted in the urine within the first 480 min after its administration. Thrombocytopenia was reported as a dose-limiting toxicity for both 254-S and carboplatin. This similarity in side effects may mainly be due to the comparable pharmacokinetic behavior of these two platinum compounds.

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A total of 68 patients with non-small-cell lung cancer who either had not previously been treated (38) or had undergone prior therapy (30) were treated in a phase II study of (glycolate-O,O') diammineplatinum(II) (NSC 375 101D; 254-S), a new platinum complex. The drug was given as a single intravenous infusion at a dose of 100 mg/m2 every 4 weeks. All 68 patients could be evaluated for response and 62, for toxicity. Objective responses were seen in 10 of 68 cases (14.7%; 95% confidence interval, 7.3%-25.4%), and the median duration of response was 15 weeks (range, 8-23 weeks). The response rates were similar for previously untreated and treated patients (13% and 17%, respectively), including three previously treated with cisplatin. Myelosuppression was the dose-limiting toxicity. Thrombocytopenia (less than 100,000 platelets/mm3) and leukocytopenia (less than 3,000 WBC/mm3) were observed in 22 (35%) and 18 (29%) patients, respectively. Mild to moderate nausea and vomiting occurred in 45 cases (73%). No significant renal or neurotoxicity was observed. We conclude that as a single agent, 254-S is well tolerated but appears to have marginal activity against non-small-cell lung cancer.

A wide variety of ions and molecules can be accommodated in the framework structure of Prussian blue (PB) and its analogs (PBAs). Mono-and polyvalent ions accommodated in the PB framework structure and PBAs can be extracted or re-inserted by redox reactions of transition metal ions composing the framework for charge compensation. In the present work, we report the detailed mechanism of the electrochemical inseration/extraction of Mg 2+ ions and the effect of anions on the redox chemistry of a PBA composed of Cu and Fe ions by electrochemical quartz crystal microbalance and X-ray absorption spectroscopy. Furthermore, we evaluated the PBA as an active material using aqueous and organic electrolytes for Mg battery systems, and clarified that the redox potential of CuFe-PBA is approximately 3 V vs. Mg/Mg 2+ in both aqueous and organic electrolytes. Rechargeable Mg batteries have received intensive attention as affordable rechargeable batteries with high electromotive force, high energy density, and high safety because of the following superb properties of Mg; Mg possesses two valence electrons and has the lowest standard electrode potential (ca. −2.36 V vs. SHE) among the airstable metals; 1,2 Mg metal can be used as an active material because Mg metal hardly forms dendrites; 3-6 and Mg is a lightweight and abundant element widely spread in the world. However, the slow diffusion of Mg 2+ ions in solid crystals prevents the realization of active materials for Mg rechargeable batteries at room temperature. Although some complex oxides have been reported to work as active materials at higher temperatures, [7][8][9][10] Chevrel compounds are still the gold standards, which work at room temperature.11,12 However, the working voltage of the magnesium battery using a Chevrel compound for the positive electrode is only ca. 1.2 V, which is far below that of lithium ion batteries (3-5 V). Nevertheless, Chevrel compounds have the significant advantage that a relatively large space exists in the crystal structure, which allows for fast Mg 2+ ion diffusion. On the other hand, since Neff first reported the redox behavior of a Prussian blue (PB)-modified electrode with rapid color change, 13 the structures, electronic and optical properties, and redox behaviors of PB and its analogs (PBAs) have been thoroughly investigated. [14][15][16][17][18][19][20][21][22][23][24][25] As shown in Fig. 1 2+ ions? Why do several peaks appear in voltammograms of these compounds? In the present study, to answer these questions, we investigated the insertion and extraction behavior of Mg 2+ ions in a CuFe-PBA using electrochemical quartz crystal microbalance (EQCM) and X-ray absorption spectroscopy (XAS). This work is expected to provide guidance for choosing framework compounds as active materials for Mg 2+ batteries. * Electrochemical Society Active Member. z E-mail: s-yagi@21c.osakafu-u.ac.jp ExperimentalSynthesis of a Prussian blue analog CuFe-PBA.-All chemicals for the synthesis of CuFe-PBA and electrochemical tests in aqueous electrolytes wer...

Introduction: Programmed cell death-1 (PD-1) inhibitors effectively treat NSCLC and prolong survival. Robust biomarkers for predicting clinical benefits of good response and long survival with anti-PD-1 therapy have yet to be identified; therefore, predictive biomarkers are needed to select patients with benefits.

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