Personalized Treatment Response Assessment for Rare Childhood Tumors Using Microcalorimetry-Exemplified by Use of Carbonic Anhydrase IX and Aquaporin 1 Inhibitors.

We present a novel approach to a personalized therapeutic concept for solid tumors. We illustrate this on a rare childhood tumor for which only a generalized treatment concept exists using carbonic anhydrase IX and aquaporin 1 inhibitors. The use of microcalorimetry as a refined in vitro method for evaluation of drug susceptibility in organotypic slice culture has not previously been established. Rapid microcalorimetric drug response assessment can refine a general treatment concept when it is applied in cases in which tumors do not respond to conventional chemo-radiation treatment. For solid tumors, which do not respond to classical treatment, and especially for rare tumors without an established protocol rapid microcalorimetric drug response testing presents an elegant novel approach to test alternative therapeutic approaches. While improved treatment concepts have led to improved outcome over the past decades, the prognosis of high risk disease is still poor and rethinking of clinical trial design is necessary. A small patient population combined with the necessity to assess experimental therapies for rare solid tumors rather at the time of diagnosis than in relapsed or refractory patients provides great challenges. The possibility to rapidly compare established protocols with innovative therapeutics presents an elegant novel approach to refine and personalize treatment.

Metabolic acidosis with topiramate and zonisamide: an assessment of its severity and predictors.

OBJECTIVE: Carbonic anhydrase (CA) inhibitors topiramate and zonisamide can induce metabolic acidosis in some patients. Our aims were to assess the prevalence and severity of this acidosis and to determine its predictors. METHODS: For 70 patients established on treatment with topiramate (n=55) or zonisamide (n=14) or both (n=1), we measured electrolytes, and genotyped single nucleotide polymorphisms (SNPs) in the main renal CA isoenzymes (II, IV and XII). RESULTS: Twenty-six percent of patients had a metabolic acidosis (serum bicarbonate <20 mmol/l). The mean serum bicarbonate of patients taking topiramate was significantly lower than those taking zonisamide (P=0.002). We found no association between serum bicarbonate and the dose of drug or the duration of treatment. Serum bicarbonate levels were associated with the CA type XII SNPs rs2306719 (P=0.006 by one-way analysis of variance) and rs4984241 (P=0.015), but this association was not strong enough to survive correction for multiple testing. CONCLUSION: The development of acidosis with topiramate and zonisamide is not determined by drug dose or by treatment duration, but may be influenced by polymorphisms in the gene for CA type XII. The aforementioned SNPs lie 9.8 kb apart in intron 1 of the CA type XII gene, and deserve further study in a larger cohort of patients.

Primary drug treatment for glaucoma: beta-blockers versus other medications.

This set of Viewpoints articles examines the merits of beta-blockers versus other medications as the primary drug treatment for glaucoma. Ophthalmologists must balance issues such as efficacy, compliance, cost, and side effects when deciding on the appropriate medication to prescribe. Dr. Stamper stresses the advantages of tailoring the choice of medication to the needs of the individual patient. Drs. Wigginton and Higginbotham review the benefits of beta-blockers and present some of the disadvantages of the non-beta-blocker class of medications.

A risk-benefit assessment of drugs used in the management of glaucoma.

All antiglaucoma drugs are able to lower intraocular pressure (IOP) to variable degrees. However, all of them can possibly produce ocular and/or systemic adverse effects, some of which are not acceptable. Therefore, the drug or the combination of drugs which is efficacious enough to achieve the target IOP and have no or negligible adverse effects should be identified for each glaucoma patient, considering their ocular (e.g. the stage of glaucomatous damage, refraction) and systemic (e.g. age, cardiovascular disease) conditions.