Effects of the leucovorin shortage: Pilot study investigating cost, efficacy, and toxicity comparison of low fixed-dose versus body surface area-adjusted leucovorin dosing in patients with resectable colon or metastatic colorectal cancer

Abstract

Purpose As a result of the leucovorin shortage, we switched from BSA-adjusted to low fixed-dose leucovorin in patients with colon cancer receiving fluorouracil-containing therapy. Methods A retrospective, pilot study of adults receiving intravenous leucovorin as part of a fluorouracil-containing treatment was conducted including individuals with stage II or III colon or newly diagnosed metastatic colorectal cancer. One low fixed-dose (leucovorin 50 mg) patient was matched by the investigator to one BSA-adjusted (leucovorin 200-500 mg/m/dose) patient on disease stage and age. The objectives were to compare cost of alternative dosing strategies as well as efficacy and adverse event rates. Only patients being treated in the first-line metastatic colorectal cancer setting were included in the efficacy analysis. Results Fifty-eight patients were included. Leucovorin cost was reduced by 7- to 14-fold, and we were able to conserve a total of 1580-3400 doses of leucovorin by changing to fixed-dose (estimated from 200 mg/m or 400 mg/m dosing strategies, respectively). No statistically significant differences in progression-free survival ( p = 0.254), overall survival ( p = 0.923), or complications resulted. Conclusion Our decision to reduce the dose of leucovorin allowed us to conserve supply and control cost. The small sample size did not allow us to detect differences in efficacy or adverse event rates, and thus a larger study would be required to confirm our findings that efficacy was not compromised nor adverse effects greater.

Is antihistaminergic H2 really useful in prevention of hypersensitivity induced by paclitaxel?

“…However and interestingly, successive drug shortages have refocused oncology specialists on evidence-based medicine (EBM) [4]. For example, folate shortage has pushed oncology practitioners to experiment a standardized low dose protocol, and first results appear to be consistent with a similar efficacy [5]. After the discovery of paclitaxel as an antimitotic drug, the first clinical trials with paclitaxel have revealed a high rate of HSR (up to 40 %) [7].…”

Low-dose versus Standard-Dose Leucovorin in the Treatment of Colon Cancer: Mansoura University Clinical Experience in Facing the Problem of Leucovorin Shortage

“…Drug shortage problem has become a national health care disaster. It is an increasing crisis in the United States of America (USA) that adversely affects health care quality and causes elevation of health care costs 1,2 . The Food and Drug Administration (FDA) of the USA recorded 61 drug shortage incidents in 2005 which increased to 178 in 2010 3,4 .…”

“…Contributing factors to drug shortages may include manufacturing quality aspects e.g. contamination, regularity issues, business decisions or disturbances within the supply chain 1,2,6 .…”

“…The increasing severity of the problem has warranted health care organizations to put a management strategy to prioritize treatment and also to provide substitutions to treatment plans. This includes clear decisions and steps for collecting data and decisionmaking 1,11 .…”

“…It is folic acid in a reduced form used in many chemotherapy protocols. Leucovorin is used with 5-fluorouracil in many protocols for gastrointestinal tumors and for many hematologic cancers as a rescue for high dose chemotherapy such as methotrexate 1,12 .…”