Drug therapy
Chemotherapy for Brain Tumors
Introduction
In patients with a brain tumor, such as a glioma, there is a significant risk of recurrence or relapse after treatment with surgery and/or radiation therapy. This is because these treatments do not guarantee complete removal of all tumor cells. Furthermore, gliomas are invasive, infiltrating parts of the brain. Therefore, systemic treatment is necessary to reach all malignant cells in the brain. Although even systemic therapy does not eliminate all tumor cells, this approach does contribute to an improved prognosis.
Standard Chemotherapy
Since 2006, temozolomide (brand name Temodal) has been the only approved and reimbursable cytostatic drug for brain tumors. Temozolomide penetrates and kills cancer cells. The standard administration follows the so-called "Stupp regimen": five days a month for several months, in tablet form. The Perry regimen is often used for older patients. Both regimens are primarily used for glioblastomas. For IDH-mutated gliomas, the "CATNON regimen" is used, which involves radiotherapy followed by one year of Temodal administered on a 5/28-day schedule. The PCV regimen is used, for example, for oligodendrogliomas.
Alternatives when Temozolomide doesn't work
If temozolomide is ineffective or if tolerance or resistance develops, there are other drug treatment options. If no registered or reimbursed medication is available, patients may still be able to receive treatment through off-label use, compassionate use, or participation in a clinical trial.
Off-label and On-label Use
Off-label use refers to the use of medications for a type of cancer other than the one for which they were originally developed. At the doctor's request, this medication can sometimes be partially reimbursed by the Special Solidarity Fund, established specifically for serious rare diseases for which insufficient treatment options exist.
In addition, there is also on-label use in Belgium. An example of this is lomustine (whether or not in the PCV regimen), which is routinely reimbursed as neoadjuvant and adjuvant treatment for low-grade gliomas, and as second-line treatment after failure of Temodal in glioblastomas. In the latter context, expectations are limited. Lomustine is often used as a comparator in clinical trials due to its relatively low cost, but so far, no better treatment has been found in this setting.
Compassionate Use
Compassionate use involves pharmaceutical companies providing medications free of charge, usually for rare, low-incidence conditions.
Experimental Treatments: Clinical Studies
A clinical trial is a scientific study of new medication and takes place in several phases:
• Phase I: Toxicity studies in humans after activity has been demonstrated in models and animal studies. This involves identifying the ideal dose and initial signs of efficacy. Sometimes a drug turns out to have too many side effects or to be insufficiently effective.
• Phase II: Efficacy study in a limited number of patients (40 to 100), with the aim of demonstrating that the drug works in a relevant number of patients.
• Phase III: Randomized trial in large patient groups (500 to 1000). Half of the patients receive the new treatment, the other half a placebo or standard treatment. This allows for scientifically sound comparisons. For rare cancers, finding sufficient patients is challenging, and the costs are high, sometimes limiting commercial interest. A positive Phase III trial with proven patient benefit usually forms the basis for registration and reimbursement in Belgium.
• Phase IV: Post-registration study.
Considerations and Advice
The entire clinical trial process is designed with patient safety in mind. While this is essential, it should not hinder patients with life-threatening illnesses from accessing new treatments. There are calls for more flexible registration procedures and more research into off-label use. At the same time, striking the balance between protecting patients and offering new therapeutic options remains a challenge. Each situation requires an individual assessment, taking various factors into account.
Practical Advice
Oncologists at referral centers are well-informed about the possibilities of off-label use, compassionate use, and clinical trials. Feel free to ask your doctor if you experience a relapse or recurrence despite treatment.
