Survival outcomes in patients with non-small-cell lung cancer treated with erlotinib.

Erlotinib is used to treat non-small-cell lung cancer (NSCLC). Erlotinib was subsidized on the Pharmaceutical Benefits Schedule in Australia for the treatment of advanced stage (IIIB or IV) NSCLC (August 2008). In the pivotal trial supporting initial subsidy, erlotinib increased overall survival (OS) by 2 months compared with placebo (adjusted hazard ratio, 0.70; 95% confidence interval: 0.58-0.85). We examined the effectiveness of erlotinib in a 'real-world' setting by measuring survival outcomes in NSCLC patients treated in two tertiary metropolitan public hospitals in Queensland. We extracted data from the electronic oncology prescribing system (CHARM) for NSCLC patients prescribed erlotinib (1 September 2009 to 1 February 2015). Survival estimates and analyses were generated using Kaplan-Meier curves. 134 patients received at least one dose of erlotinib during the study period. At the date of data extraction 113 patients had died. The median patient age was 64 years and 55% were men. The median duration of treatment was 2.0 months. The median OS was 5.8 months. The median progression-free survival (time from start of erlotinib to disease progression or death from any cause) was 3.6 months. The use of erlotinib in the two Queensland sites was consistent with the pivotal trial used to support subsidy. The median OS was somewhat less than the trial (5.8 vs. 6.7 months), which could be because of the hospital cohort including frailer patients who were unsuitable for parenteral chemotherapy, and the mixed epidermal growth factor receptor mutation status of the hospital cohort.

Glomerular Filtration Rate Measurement and Chemotherapy Dosing.

Many chemotherapeutic drugs used to treat malignancies undergo renal clearance. Thus, accurate knowledge of kidney function is critical to ensure proper dosing, maximize efficacy, and minimize toxicity of drugs that often have a narrow therapeutic index. Making this issue more salient is the fact that impaired kidney function, as assessed by glomerular filtration rate (GFR), is encountered commonly in patients with cancer. Recent data and expert guidelines recommend the use of the Chronic Kidney Disease-Epidemiology Collaboration equation to guide the assessment of kidney function, except when directly measured GFR is clinically necessary. Controversies regarding the measurement of kidney function include the use of race in this equation, indexing to body surface area, and dosing of medications based on stages of chronic kidney disease versus more discrete values of estimated GFR. The development of accurate, real-time GFR measures may hold great promise in allowing for more accurate dosing of these important drugs.

Drug dosing in cancer patients with decreased kidney function: A practical approach.

Correct drug dosing of anticancer agents is essential to obtain optimal outcomes. Overdosing will result in increased toxicity, treatment interruption and possible cessation of anticancer treatment. Underdosing may result in suboptimal anti-cancer effects and may increase the risk of cancer-related mortality. As it is practical nor feasible to perform therapeutic drug monitoring for all anti-cancer drugs, kidney function is used to guide drug dosing for those drugs whose primary mode of excretion is through the kidney. However, it is not well-established what method should be utilized to measure or estimate kidney function and the choice of method does influence treatment decisions regarding eligibility for anti-cancer drugs and their dose. In this review, we will provide an overview regarding the importance of drug dosing, the preferred method to determine kidney function and a practical approach to drug dosing of anticancer drugs.