The Cisplatin Shortage
How does it affect treatment?
Obligatory—This is not medical advice
While much of the current focus in cancer medicine revolves around the future, it's important to recognize the continued effectiveness of older agents. One such agent is doxorubicin, which remains the standard of care for many patients with advanced sarcoma. Its approval by the FDA dates back to 1974. Another drug, cisplatin, approved in 1978, has recently garnered attention due to a shortage. Within the realm of sarcoma treatment, cisplatin is commonly used for bone cancers like osteosarcoma, as well as other cancer diagnoses. In fact, a comprehensive review of the National Comprehensive Cancer Network guidelines reveals that there are 230 distinct chemotherapy plans incorporating cisplatin. While cisplatin does have its associated toxicities, it offers broad curative efficacy and is highly regarded among oncologists. If an oncologist were to be stranded on a proverbial desert island and had to choose from available medications, cisplatin would likely be high on their list. Its importance is particularly pronounced in curing conditions that affect younger patients, making its overall net benefit proportionally significant when compared to other treatment options.
What is Cisplatin?
The name "cisplatin" itself hints at its distinctive feature as a platinum-based compound. In fact, Rosenberg's seminal 1970 paper included a figure showcasing the chemical structures of different substances tested in the laboratory, revealing their potential antineoplastic effects.1 See below
Years, later its mechanism was discovered to be causation of DNA inter-strand crosslinks. Due to the nature of the practice and drug development within oncology at that time, there was a rapid implementation of early trials in humans which demonstrated efficacy. I won’t belabor it all here, but suffice it to say, there was tremendous excitement for cisplatin, and this led to rapid uptake.
For a review of the effectiveness of cisplatin for patients with osteosarcoma, see this prior post. I have included a link for those not wanting to leave this page here.
Why did this happen?
The reasons are varied. The American Society for Health-Systems Pharmacists has enumerated them for each manufacturer (as of 6/12/2023).
It is important to acknowledge that the current lack of availability of cisplatin or carboplatin is likely not attributable to a single direct cause. While there may be various arguments proposed to address this issue, the reality is that most cancer centers will probably be without access to these drugs for the next few months. This predicament has placed oncologists and their patients in a challenging situation, as they navigate the treatment options available to them.
Are there alternatives?
Regrettably, there is currently no alternative agent that can precisely replace cisplatin for the treatment of bone sarcomas. Ideally, patients and healthcare providers would not be faced with the uncertainty that arises when the standard of care is unclear. However, at UCSF, for the time being, patients with osteosarcoma have been able to receive treatment with AP (doxorubicin and cisplatin) or MAP (methotrexate, doxorubicin, and cisplatin) regimens. I have had discussions with other sarcoma oncologists who have transitioned to regimens used for soft tissue sarcomas, such as AIM (doxorubicin, ifosfamide, and mesna), particularly for patients receiving adjuvant therapy and for those who may have difficulty tolerating cisplatin. This decision is based on the knowledge of ifosfamide's efficacy in patients with bone sarcomas when combined with etoposide. They are attempting to make the best of a challenging situation. For patients with advanced disease, a shortage might lead to a different sequence of treatments.
Final Thoughts
Undoubtedly, cisplatin holds significant importance as a medication in the field of oncology, particularly for the treatment of bone sarcomas. Its established efficacy and high curative potential have made it a crucial component of sarcoma treatment protocols. The scarcity of cisplatin may last for months. While there is no exact substitute, some oncologists have had open discussions with their patients about alternative regimens in various settings. As oncologists and their patients continue to grapple with the shortage, root cause analysis should be performed, and future steps should be taken to prevent this from happening in the future.
https://aacrjournals.org/cancerres/article/30/6/1799/478042/The-Successful-Regression-of-Large-Solid-Sarcoma