Linda Hamata

Novel agents improve survival of transplant patients with multiple myeloma including those with high-risk disease defined by early relapse (<12 months)

The treatment of multiple myeloma (MM) has changed with the advent of thalidomide, bortezomib, and lenalidomide, the so-called novel agents (NAs). Given the complexity of MM therapy in the NA era we pursued a population based study to assess for improvements in survival as well as to characterize the relevance of early relapse (within 12 months) and the International Staging System in this clinical setting. We reviewed our experience with 460 patients with MM treated with autologous stem cell transplant (ASCT) between 1988 and 2008, of whom 306 had relapsed. The cohort was divided into two groups based upon relapse pre-2004 and relapse during/after 2004 (2004+), which correlated to availability of bortezomib and lenalidomide. Improvements in both overall survival (OS) (median 32.0 months vs. 71.8 months; p < 0.001) and post-relapse survival (PRS) (median 15.2 months vs. 42.8 months; p < 0.001) correlated with the NA era. Exposure to NAs conferred a better PRS (median 35.7 months vs. 9.1 months; p < 0.001). Although all patients had improvements in survival, those who relapsed late continued to do better. Lastly, in the NA era, the ISS remains an important prognostic tool in relapse, but only in the late relapsing cohort.

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.

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

Etoposide intravenous solution is associated with leaching of diethylhexyl phthalate (DEHP) from bags and tubings made from polyvinyl chloride (PVC). Recent evidence suggests that this may be more substantial than previously found. Since DEHP is potentially hepatotoxic and carcinogenic, it is preferable to prepare and administer etopo-side bags and tubings made from non-PVC materials.

Challenges of dispensing costly tablets with short shelf-life

Afatinib, trametinib and regorafenib are three costly oral oncology drugs with a short shelf-life after the original container has been opened. Their short shelf-lives are due to degradation on exposure to moisture. Therefore, manufacturers recommend them to be dispensed in the original packaging with the desiccant. However, the prescribed quantities do not always match the quantities in the original packaging, usually because of dose modifications for toxicities. This leads to potentially significant drug wastage and financial losses. We describe some potential approaches to this issue.