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Magnesium alterations and pharmacokinetic data in gallium-treated lung cancer patients

Authors:
  • Société de Coordination de Recherches Thérapeutiques

Abstract

The dose of gallium chloride required to inhibit tumor growth after oral and chronic administration depends on the stage of the cancer disease and of the type of metastases. A dose regimen of 800 mg/24 h of gallium chloride will provide serum gallium concentrations greater than or equal to 600 micrograms/l in lung cancer patients with a small and limited disease. A dose of 1,400 mg/24 h is well tolerated in metastatic patients but may not be high enough to reach the desired serum gallium concentrations especially in patients with bone metastases. Radiotherapy and/or a chemotherapy will permit one to increase the serum gallium concentrations and the tumor gallium uptake by reducing the volume of the tumor. After chronic, oral administration of gallium a decrease in RBC Mg is noted. To avoid the Mg deficiency, the treatment must not be interrupted and may perhaps be decreased with care and slowly without resulting in a decrease of the serum gallium concentrations provided the treatment has been prolonged over a sufficient time to enable one to induce intratumor biological modifications and a decrease in the number of the malignant cells. Acute pharmacokinetic data are related to the histologic type of the tumor and may not be used to predict the serum gallium concentrations after chronic administration. The serum gallium concentrations required to inhibit the tumor growth may be higher in small cell lung carcinomas than in nonsmall cell lung carcinomas. Frequent Mg and Ga blood determinations are necessary to manage effective gallium treatment.
... O tratamento foi feito por 15 dias em 18 pacientes com câncer de pulmão, numa faixa de doses de 100 a 1400 mg/dia (18). Logo depois desse período alcançou-se um nível de concentração estacionário (371 ± 142 ng/mL) no sangue dos pacientes que não desenvolveram metástase, ao contrário daqueles que desenvolveram (nível de gálio no sangue insignificante) [45]. As concentrações reportadas foram consideradas demasiado altas para GC para ser usado como agente único no câncer, por isso estudos posteriores em pacientes com câncer de pulmão utilizaram associações com cisplatina [46]. ...
Thesis
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Trivalent aluminum gallium derivatives with siderophores desferrioxamine (dfo) and desferrioxamine-caffeine (dfcaf) were prepared and characterized in solution using mass spectroscopy, cyclic voltammetry, vibrational spectroscopy and 1 H nuclear magnetic resonance. Further confirmation of the formation of MeL (Me = Al3+, Ga3+, L = dfo or dfcaf) was obtained through competitive equilibria with the fluorimetric probes 8-quinoline and fluorescent desferrioxamine. It was observed that MeL complexes are stable in solution, and that aluminum derivatives are more stable than gallium. Also through interaction with calcein-iron complex, it was observed that MeL formed in solution. Preliminary docking studies show that complexes derived from dfcaf may have the same internalization mechanism in Escherichia coli as other iron-carrier antibiotics. The "Trojan horse effect" is the selective loading of toxic ions through the iron uptake system of microorganisms mediated by siderophores. The biological activity of MeL complexes was studied by growth inhibition of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. In general, dfcaf is more active than dfo possibly due to its increased lipophilicity. MeL complexes were generally more active than the metals or ligands separately, possibly by absorption of toxic ions facilitated by siderophores, demonstrating the "Trojan horse effect”. The Gram-positive bacterium S. aureus showed greater resistance than Gram-negative bacteria , and interestingly the fungus C. albicans was sensitive to these treatments. These results show the possibility of using such metallodrugs as a treatment for microbial infections.
... Plasma Ga concentrations depend on the tumor mass (74), the plasma transferrin concentration, the presence or not of metastases (75), the type of the primary tumor and the type of metastases (76), but also on the Ga ligand (30,33). It does not appear possible to manage plasma Ga concentration by monitoring the dose of the GaCl 3 treatment, but rather to use the plasma Ga concentration as a marker of the efficacy of therapy. ...
... Mild reductions in hemoglobin and magnesium were observed. 121 The maximum accessible serum concentrations were deemed too low for GC to be used as a single agent in lung cancer. 18 Possible potentiation of cisplatin and etoposide therapy by GC in lung cancer patients was reported. ...
... Mild reductions in hemoglobin and magnesium were observed. 121 The maximum accessible serum concentrations were deemed too low for GC to be used as a single agent in lung cancer. 18 Possible potentiation of cisplatin and etoposide therapy by GC in lung cancer patients was reported. ...
Chapter
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IntroductionChemistry and Mechanisms of ActionTherapeutic Gallium CompoundsAbbreviations UsedReferences
... Plasma Ga concentrations depend on the tumor mass (74), the plasma transferrin concentration, the presence or not of metastases (75), the type of the primary tumor and the type of metastases (76), but also on the Ga ligand (30,33). It does not appear possible to manage plasma Ga concentration by monitoring the dose of the GaCl 3 treatment, but rather to use the plasma Ga concentration as a marker of the efficacy of therapy. ...
Article
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Chapter
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