Mário L de Lemos

Evaluation of creatinine-based formulas in dosing adjustment of cancer drugs other than carboplatin

Background. Glomerular filtration rate (GFR) is often used to determine initial dosing of renally excreted cancer drugs. GFR can be calculated using the Cockcroft-Gault (CG) or the modified diet in renal diseases (MDRD) study formulas, both of which are based on serum creatinine levels. The MDRD formula is more accurate in noncancer patients, does not require patient weight, and is reported automatically by all laboratories in British Columbia, Canada. We previously showed that the CG and MDRD formulas have similar accuracy for carboplatin dosing in patients with gynecological malignancies. We now examine dosing of all renally excreted cancer drugs in the general cancer population. Since this setting does not include routine measurement of GFR, we report the concordance of estimates of GFR derived from the CG and MDRD formulas. Methods. Patient data were collected retrospectively at the BC Cancer Agency. The primary outcome was the proportion of patients who would have received a different initial dose due to difference in the GFR. Each patient’s dose was determined from dose adjustment tables stated in specific treatment protocols. The secondary outcome was concordance of the GFR derived from CG and MDRD, using the method of Bland and Altman. A difference of >30% was assumed to be clinically significant because this difference would usually lead to dose adjustment based on reclassification of renal function. Results. A total of 313 patients were evaluated, with 40% male. The median age was 56 years, weight 67.5 kg, height 166 cm, and serum creatinine 74 µmol/L (0.84 mg/dL). The median GFR derived from the CG and MDRD formulas were 86.8 mL/min (mean 91 mL/min, SD ± 30 mL/min) and 87.6 mL/min (mean 88 mL/min, SD ± 26 mL/min), respectively. A total of 8.6% (27/313) of patients would have received a different dose due to difference in the GFR; of these, 67% (18/27) would have received a higher dose. A difference of >30% in GFR was found in 17.9% (56/313) of patients. Conclusions. There is good concordance of the GFR derived from the CG and MDRD formulas for most cancer patients, with less than 10% of patients expected to receive a different initial dose of chemotherapy. The MDRD formula may be a reasonable alternative to the CG formula for dosing of cancer drugs which are renally excreted or nephrotoxic. J Oncol Pharm Practice (2010) 16: 113—119.

Clinical efficacy of generic imatinib.

Background Generic imatinib has recently been approved for chronic myeloid leukemia in Canada and the European Union (EU). There are anecdotal concerns of reduced efficacy related to generic vs. brand name imatinib. Methods MEDLINE and EMBASE were searched. Generic imatinib product monographs approved by Health Canada and the European Medicines Agency (EMA) were reviewed. Medical information of Novartis, Teva and Apotex were contacted. Results Several issues have been raised. First, generic imatinib approved outside Canada and the European Union has been associated with reduced efficacy in small case reports and contradictory findings with two case series. However, the clinical bioequivalence of these generic products has not been clearly established. Secondly, use of generic imatinib in other populations has been questioned. However, imatinib absorption is not significantly different in pediatric chronic myeloid leukemia or patients with gastrointestinal tumours compared to adults with chronic myeloid leukemia. Although reduced absorption was reported after gastric bypass and gastrectomy, imatinib absorption occurs mostly in the ileum, duodenum, colon and jejunum. Change in gastric acidity has also been shown to not affecting imatinib absorption. Finally, beta-crystal form of brand name imatinib is more stable than the alpha-crystal form of generic imatinib at room temperature. However, the EMA found both crystal forms to be highly soluble and polymorphism would not significantly influence the performance of generic imatinib. Conclusion Overall, anecdotal concerns appear to be unfounded for generic imatinib approved in Canada and the EU. There is no evidence that these generic imatinib products are less effective than brand name imatinib.

Stability issues of parenteral chemotherapy drugs.

The pharmacist often needs to have all the information required to prepare and to assign an expiry date for parenteral products of antineoplastic agents. The pharmaceutical manufacturers usually provide data on how to prepare their products and the associated physicochemical stability. Standard reference texts also provide additional summary information of other primary data. However, it is not uncommon to find knowledge gaps in this area. Hence, additional extrapolation and consensus on interpretation is often needed to address issues not covered by data from the pharmaceutical manufacturers, standard reference texts, or official guidelines. Some of the key issues have been identified in our recent development of a chemotherapy preparation and stability chart. These include use of data from different brands, expiry date of original vial and final products, risk of contamination, infusion volume and stability, multi-day home-use products, syringe preparations, and products to be used immediately. Potential approaches to address these common issues are described in this article. J Oncol Pharm Practice (2007) 13: 27–31.

Interaction between mercaptopurine and milk

Mercaptopurine is a purine analog used for acute lymphoblatic leukemia and chronic myelogenous leukemias. Since it is inactivated by xanthine oxidase (XO), concurrent intake of substances containing XO may potentially reduce bioavailability of mercaptopurine. Cows milk is known to contain a high level of XO. In vitro and in vivo data suggest that concurrent intake of cows milk may reduce the bioavailability of mercaptopurine. This interaction may be clinically significant. Therefore most patients should try to separate the timing of taking mercaptopurine and drinking milk. J Oncol Pharm Practice (2007) 13: 237—240.

Management of extravasation of oxaliplatin

Oxaliplatin extravasation has been associated with local pain and inflammation which may be severe and lead to complications including necrosis. Recent case reports suggest that oxaliplatin may be better classified as an irritant when extrava-sated. The optimal management of oxaliplatin extravasation however remains uncertain. Cold compress may cause local vasoconstriction and reduce cellular injury. However, it may potentially precipitate or worsen peripheral neuropathy. Warm compress may increase drug removal by local vasodilation and avoid peripheral neuropathy. However, it may potentially increase cellular uptake and hence injury. Further research into this area is needed.

Impact on patient satisfaction with a structured counselling approach on natural health products

Purpose. Natural health products (NHP) are commonly used by cancer patients. The provision of better information on NHP may improve the patient satisfaction and quality of life. We report the impact on patient satisfaction by routine counselling on NHP. Methods. Patients visiting the pharmacy of a comprehensive cancer centre for the first time were recruited before (control) and after (intervention) the introduction of routine structured counselling on NHP by pharmacists. The primary endpoint was patient satisfaction. Overall cost and cost per improvement in satisfaction were estimated. Results. 265 patients completed the questionnaires. The average age was about 60 years old, with roughly equal number of men and women. Breast and genitor-urinary cancers made up about 80% of the patients. Nearly 45% of patients had some college or university education. The scores for overall satisfaction and each subscale were all increased in the intervention group. This was statistically significant regarding information on NHP. Counselling was associated with an increase of about 9 minutes of counselling time and a mean additional cost of CDN

Use of combined androgen blockade for advanced prostate cancer in British Columbia

7.49 per patient. Conclusion. We found increased patient satisfaction with routine counselling on NHP. There was only minimal increase in workload and cost for each counselling section. J oncol pharm practice (2008) 14: 37—43.

Renal safety of 1-hour pamidronate infusion for breast cancer and multiple myeloma patients: comparison between clinical trials and population-based database.

Objectives. Initial androgen deprivation therapy (ADT) for metastatic prostate cancer with combined androgen blockade (luteinizing-hormone releasing hormone agonist [LHRH agonist] plus antiandrogen) is not recommended in British Columbia (BC). However, this is difficult to monitor since ADT includes concurrent antiandrogen for the first month of LHRH agonist to prevent disease flare. We describe the prevalence of CAB use in BC and its financial impact. Methods. This was a population-based, retrospective analysis. Patients started on LHRH agonist in January 2005 to December 2006 were identified from the BC Cancer Agency database. CAB was defined as greater than 1 month of antiandrogen concurrently with LHRH agonist. Incremental cost of CAB was based on an average 18 months of therapy from the pivotal CAB study. Incremental cost-effectiveness ratio (ICER) was based on life-year gained (LYG) from the Prostate Cancer Trialists’ Collaborative Group meta-analysis. Estimated financial impact for 2007—2008 was based on an annual increase by 5.5% in prevalence of prostate cancer in BC. Results. A total of 2751 patients were identified. CAB was used in 607 patients (22%), associated with an incremental cost of CDN

Vinorelbine and venous irritation: optimal parenteral administration

1768 and ICER of CDN

Leaching of diethylhexyl phthalate from polyvinyl chloride materials into etoposide intravenous solutions

11,220/LYG per patient. Total incremental cost was CDN