Changes in Chemotherapy Treatment Plans Made as a Result of the Etoposide Shortage

Sarah Kraus Cimino, PharmD BCOP BCPS
Hematology/Oncology Clinical Pharmacy Specialist
Pennsylvania Hospital
Philadelphia, PA

Drug shortages have been unrelenting during the past 10 years, with 1,950 new drug shortages occurring from 2008 to 2018. Chemotherapy is consistently among the top five most common drug classes on shortage.¹ Chemotherapy drug shortages are of particular concern because the number of comparable therapeutic alternatives are limited. Specific chemotherapy drugs that have had shortages in the past 10 years include fluorouracil, cytarabine, and liposomal doxorubicin.^2,3

In 2018, a national shortage of etoposide injection occurred, requiring conservation strategies to be employed at Pennsylvania Hospital in Philadelphia, PA. Management of this drug shortage required a coordinated effort among prescribers, pharmacists, and drug suppliers. Because of the severity of the shortage, mitigation plans were also discussed across the health system, and a local strategy was approved through the hospital’s Ethics Committee and Pharmacy and Therapeutics Committee. The decision was made to prioritize etoposide supply for patients receiving treatment with curative intent. However, treatment was not withheld from other patients if supply was available.

Difficult decisions like these in response to drug shortages have the potential to affect patient care. Most of the literature on oncology drug shortages consists of provider surveys that report increased medication errors, increased costs, and the need for modification of therapy as a result of drug shortages.^2,3 Unfortunately, empirical data on the consequences of oncology drug shortages are sparse.

A 2018 study aimed to describe the clinical impact of the etoposide injection shortage. This single-center retrospective study consisted of chart review for patients treated between January and August 2018.⁴ Patients were included if they had been prescribed an etoposide-containing chemotherapy regimen. The study timeframe was selected because the etoposide shortage at the institution was the most critical during this time. The primary aim of the study was to determine the percentage of patients who required a change in therapy during the shortage. Change in therapy was defined as (1) use of an alternative therapy other than etoposide injection, which included switching the patient to oral etoposide or Etopophos injection, or (2) omission of therapy, where the patient did not receive any formulation of etoposide in at least one treatment cycle. Secondary endpoints were assessed between two subgroups: patients who received etoposide injection and patients who received alternative etoposide formulations (oral etoposide or Etopophos injection). Secondary endpoints included incidence of adverse drug events, medication errors, delays of 3 days or more for scheduled chemotherapy, progression of disease, and associated drug costs.

A total of 22 patients were included in the study. The mean age was 60 years, and the most common types of cancer were lung cancer (n = 10), sarcoma (n = 6), and non-Hodgkin lymphoma (n = 4). For the primary endpoint, seven (32%) patients required a change in treatment during the etoposide injection shortage. Six (27%) patients received an alternative formulation of etoposide, and etoposide was withheld for one patient.

No significant difference was seen in secondary endpoints between patients who received etoposide and those who received alternative etoposide formulations. This included no difference in incidence of side effects (100% vs. 100%, p = 1.00), medication errors (0% vs. 0%, p = 1.00), treatment delays (7% vs. 0%, p = 1.00), or disease progression (53% vs. 33%, p = 0.64). The average wholesale acquisition cost for etoposide per cycle per patient was considerably higher for patients who received alternative formulations of etoposide ($58 USD for standard etoposide vs. $806 USD for alternative formulations).

To our knowledge, this was the first study to characterize the clinical impact of the etoposide injection shortage. At this institution, etoposide supply was prioritized and allocated on a cycle-by-cycle basis for patients. Other strategies include allocating the drug on a dose-by-dose basis or reserving the amount required to complete a full treatment course. In this study, approximately one-third of patients required a change in their chemotherapy treatment plan because of the shortage.

In an earlier study Becker and colleagues reported that 9.8% of patients required alternative therapy because of an oncology drug shortage. They also reported decreased use of drugs on shortage compared to historical use, which may indicate that a higher percentage of patients were actually affected.⁵ In this study, one patient had treatment with etoposide omitted because of a delay in insurance approval for oral etoposide, and another patient had a delay in treatment. This second patient was scheduled to receive an autologous stem cell transplant with an etoposide-based conditioning regimen, but the transplant was delayed because of an inadequate supply of etoposide. Both scenarios reveal the possibility that consequences of oncology drug shortages are underreported. This earlier study by Becker and colleagues had notable limitations, including the small sample size from a single institution. Furthermore, the study was unable to capture patients who had never been prescribed etoposide and instead were initiated on alternative regimens because the prescriber had knowledge of the etoposide shortage.⁵

It seems that no end to chemotherapy drug shortages is in sight. As part of an attempt to design a plan to eradicate drug shortages, the U.S. Food and Drug Administration Drug Shortages Task Force urges “quantification of the harms of drug shortages, particularly those that lead to worsened health outcomes for patients and increased cost for health care providers.”⁶ Further research to characterize the impact that oncology drug shortages have on patients is needed as an impetus for change. 

References

1. American Society of Health-System Pharmacists. Drug shortages statistics. Available at https://www.ashp.org/Drug-Shortages/Shortage-Resources/Drug-Shortages-Statistics. Accessed November 22, 2019.
2. McBride A, Holle LM, Westendorf C, et al. National survey on the effect of oncology drug shortages on cancer care. Am J Health Syst Pharm. 2013;70:609-617.
3. Gogineni K, Shuman KL, Emanuel EJ. Survey on oncologists about shortages of cancer drugs. N Engl J Med. 2013;369:2463-2464.
4. Li H, Cimino SK. Clinical impact of the etoposide injection shortage. J Oncol Pharm Pract. 2020;26:187-192.
5. Becker DJ, Talwar S, Levy BP, et al. Impact of oncology drug shortages on patient therapy: unplanned treatment changes. J Oncol Pract. 2013;9:e122-e128.
6. U.S. Food and Drug Administration. Drug shortages: root causes and potential solutions 2019. Available at https://www.fda.gov/media/131130/download. Accessed November 25, 2019.