There is widespread off-label use of drugs for cancer treatments, many times with little to no evidence of clinical benefit. A meta-analysis of clinical studies indicated off-label drug use in 13-71% of adult cancer patients. Off-label use was higher in patients with metastatic disease and in palliative care, who have exhausted all other standard of care options.
Cancer treatment is mostly based on clinical guidelines from different organizations such as NCCN (National Comprehensive Cancer Network), ASCO (American Society of Clinical Oncology) and others. These guidelines are determined through scientific evidence and regulatory qualifications and approvals, for specific cancer indications, stage and nature of the cancer, whether newly diagnosed, relapsed, refractory or spread (metastasized) to other regions. Despite evidence-based treatment guidelines, there is a significant and widespread off-label use of drugs in many diseases including cancer (Repucci N, J of Health Care Compliance, 2011).
Off-label Drugs for Cancer Treatment
Off-label use of drugs is where the drug is being prescribed in an indication, patient population or context not consistent with the prescribing information approved by the regulatory authorities. One study has shown that 73% of off-label prescription drug was not supported by scientific evidence of clinical efficacy benefit (Radley DC et al, Archives of Internal Medicine, 2006). In this blog, variations and reasons for off-label drug use and issues around the same will be discussed.
Off-label drug use could be use of the drug in an indication it was not tested and approved for, use in an unapproved line of treatment or using the drug with differences in the route of administration or dosage from what it was originally approved for. There is a difference between off-label use that pertains to an approved drug vs. compassionate use that provides access to investigational drugs to patients with life-threatening diseases who do not have other options. Off-label drug use also does not include the use of unlicensed therapeutic product that has not gone through any regulatory approval. Some key issues around off-label drug use are the uncertainty of clinical benefits and possible toxicities in an untested population, and increased out of pocket costs for the patient since the off-label drugs are usually not covered by health insurance providers.
A study done by the Department of Pharmacy, at the National University of Singapore, examined peer reviewed published studies between 1975 to 2016 on off-label drug use in cancer treatment, and zoomed into 23 of the 199 shortlisted studies for their analysis (Saiyed MM et al., J of Clin Pharm & Ther., 2017). Some of the interesting findings of their analysis are:
- Off-label drug use is commonly practiced across all cancer types.
- Off-label drug use for hospitalized cancer inpatients was between 18-41%.
- Off-label drug use in adult cancer patients ranged between 13-71%.
- Off label drug use is comparatively higher in metastatic patients (33-65%) and palliative care patients (34-76%), who have exhausted all other standard of care options.
- Off-label cancer drug use was significantly higher in breast cancer patients with off-label regiments in stages 1, 2, 3 and 4 breast cancer patients being 70, 76, 74 and 82% respectively as per estimates from SEER medicare data (Eaton et al, J Natl Compr Canc Network, 2016).
- Most commonly used off-label cancer drugs were the non-specific chemotherapy drugs that have severe side-effects, including carboplatin, doxorubicin, fluorouracil, paclitaxel, docetaxel, vinorelbine, gemcitabine and oxaliplatin.
- Most commonly used off-label targeted therapies were bevacizumab, cetuximab, rituximab, gefitinib and erlotinib.
The reason the above statistics of off-label use becomes important and significant is because they do not support the conventional claim of cancer treatment being only evidence-based and guidelines-driven. Once the drug is approved even for an orphan indication, the approved drug can be used off-label and is widely promoted for its clinical benefits. For instance, off-label use of the anti-angiogenesis drug bevacizumab in adjuvant treatment is done despite data that it provides no improvement in progression free survival (PFS) when compared to standard chemotherapy (Cameron D et al, Lancet Oncol, 2013). Additionally with the fast-track and breakthrough designation regulatory tracks for drug approval, the clinical trials for orphan indications or uncommon cancer types are often insufficiently powered in addition to using surrogate endpoints that do not measure impact on patient overall survival or quality of life improvement. In summary, there is widespread off-label use of drugs for cancer treatments, many times with little to no evidence of clinical benefit.
Cancer patients often have to deal with different chemotherapy side effects which affect their quality of life and look out for alternative therapies for cancer. Taking the right nutrition and supplements based on scientific considerations (avoiding guesswork and random selection) is the best natural remedy for cancer and treatment related side-effects.