In this part we show some examples for the off-label use in brain cancer treatment.
Sodium flourescin in brain tumor surgery
Fluorochrom sodium fluorescin (FL) is normally used for angiography in opthalmic surgery. However studies suggest that it is also useful to visualize the tumor and the extent of resection (EOR) during brain tumor surgery. FL can be used with normal white light but then high doses are needed. Using 560 nm-wavelenght flouresecent light allows for working with only small doses of FL. The FL is injected intravenously and can be directly seen under the fluoresccent light. Studies show an increased visualization of the tumor and the tumor margin because FL accumulates in vascularized tumor tissue. FL hasn't shown any allergic reactions or other side effects up to now. However, as a false-positive effect, FL accumulates in areas with scars and devitalized cerebral tissue as well. These regions especailly occur at the tumor border for pretreated tumors via surgery or radiation. [1]
Figure 1: recurrent glioblastoma under white light (a), with fluoresecent light (b) and after resection (c). [1]
Temozolomide in solid tumors in children
Temozolomide (TMZ) is a second generation of Imidazotetrazine compounds (TZC). These are alkylating agents that have antitumor potential. Studies have shown that TMZ can improve brain tumor treatment (i.e. 6% increase in survival). Therefore the FDA approved TMZ as a drug to treat high grade gliomas, however only in adults. Trials with the off-label use of TMZ in children have shown benefits as well. Many patients responded to the drug and often a stabilization of the disease was shown. However, TMZ in children also showed increased side effects compared to the treatment in adults. This especially includes thromboctopenias and haematological toxicity. Giving smaller doses on a longer run causes similar grades of toxicity compared to higher doses at less times. So the beneift-risk ratio for TMZ in children still needs to be evaluated further. [2]
Bevacizumab for high-grade gliomas
One major feature of GBMs is the process of angiogenesis. Therefore treatment reasearch is broadly done in this area. The antiangiogenic agent bevacizumab (Avastin®) binds to the vascular endothelial growth factors (VEGF) and thereby decreasing/eliminating angiogenesis. So this drug is already used in the treatment of different cancer types, including metastatic cervical and colorectal cancer. Studies and trials have shown that using bevacizumba during the treatment of GBMs has a great positive effect, increasing the progression free survival (PFS) and the overall survival time (OS). Due to these strong results many physicians treat their patients that have a GBM off-label with bevacizumab. Two of the trials done with the antibody for GBM then in 2009 led the FDA to approve bevacizumba as a drug for second-line treatment of Glioblastomas. [3] [4]
Figure 2: Kaplan-Meier curves for PFS (A) and OS (B) of all patients [3]
Bibliography
[3] P.L. Nghiemphu, MD, W. Liu, MS, Y. Lee, PhD, T. Than, BS, C. Graham, MSN, A. Lai, MD, PhD, R.M. Green, MD, W.B. Pope, MD, PhD, L.M. Liau, MD, PhD, P.S. Mischel, MD, S.F. Nelson, MD, R. Elashoff, PhD and T.F. Cloughesy, MD;
Bevacizumab and chemotherapy for recurrent glioblastoma, A single-institution experience; published in Neurology (2009)
[4] https://www.cancer.gov/about-cancer/treatment/drugs/fda-bevacizumab#Anchor-Glioblastoma