Chemotherapy • Glioma - Center Foundation

Most important issues at this stage:

There exist different ways of chemotherapy administration (oral, intravenous, intra-arterial). Unfortunately, there are also many strategies that cancerous cells use to avoid destruction by cytotoxic chemotherapy. One of them is the activity of the MGMT repair enzyme which repairs damage inflicted by chemotherapy before the cells are destroyed. Moreover, chemotherapy usually affects cells at the stage of division, and the chemical factor can be removed from the tumor before the next division process begins. Finally, the third problem is the penetration of the blood-brain barrier. Numerous chemotherapeutic substances lack the ability of such penetration, and even if they manage to get through (e.g. temozolomide), according to the test, the penetration is not complete.
Chemotherapy is effective during cell division, but at a given moment only a small part of cells divide, which means that the longer the chemotherapeutic stays within a cell, the more chance that is will be there when this cell divides. Hence experimental use of, for instance, verapamil (typically used in cardio therapy), in order to block calcium channel. Such medication leads, of course, to specific side effects, which prevents their successful use.

Chemoresistance is a serious problem in the treatment of tumors of the central nervous system; it significantly limits the applicability of chemotherapy glioblastoma patients.

Since there is no standard procedure in the treatment of patients with recurrent polymorphic glioblastoma, in view of lack of tested possibilities, different chemotherapeutics are sometimes applied, depending on the decision made by the doctor in charge. Penetration of the blood-brain barrier is relatively successful following treatment with alkylating agents – CCNU (lomustine), BCNU (carmustine), procarbazine, numustine, photoemustine, and temozolomide.

Other cytostatic substances commonly used with glioblastoma are inhibitors of topoisomerase I and II, such as irinotecan, or topotecan, or inhibitors of mitosis, such as vincristine. In general, tests do not show the advantage of multiple drug procedures over monotherapy, perhaps with the exception of the PCV schema, i.e. procarbazine, lomustine, and vincristine, but even this does not lead to many advantages.

The oral chemotherapeutic of well-documented effectiveness in the treatment of glioblastoma is temozolomide, which is part of standard procedures. Over the last few scores of years, no other oral or intravenous chemotherapeutic have been shown to positively affect therapy, and neither did clinical experiments, testing various combinations of such substances. Although the effectiveness of temozolomide is not universal, it constitutes an integral part of standard procedures in patients with a recent diagnosis. The individual response depends on promoter MGMT methylation

There are also reports on procedures in which chemotherapy is supplemented with mononuclear antibodies. The medication which is worth mentioning is bevacizumab, approved by the FDA as the treatment of recurrent tumors. Tests administered to a group of 70 patients have demonstrated that supplementing temozolomide with bevacizumab in the course of radiotherapy, followed by further administration of bevacizumab and temozolomide and supplemented with irinotecan, doubled the recurrence-free period and prolonged average survival time by over six months from the diagnosis. In another study (carried out at UCLA) comparable advantage was shown to be possible following administration of bevacizumab only after the recurrent tumor was detected. Finally, the medication was officially approved by the FDA as applicable precisely in patients with recurrent tumors. However, it should be added that even though it does not prolong average overall survival if administered in the course of primary radiotherapy, it extends progression-free period and thus proves advantageous in improving patients’ quality of life. In the European Union bevacizumab is not registered as a drug to treat brain tumors, but it may still be used in off-label treatment. Its operation (bevacizumab is an anti-VEGF inhibitor) consists of inhibiting the emergence of blood vessels inside the tumor, due to binding with the growth factor in endothelial vessels (VEGF).

As is well known, chemotherapy, especially intravenous, strongly influences the patient’s quality of life and causes numerous side effects. In view of its doubtful efficacy, advantages and disadvantages of malignant glioblastoma treatment should be thoroughly discussed with the doctor in charge, so that decisions are made with all responsibility.

On the other hand, what should be considered is super selective intra-arterial chemotherapy, which exerts no adverse general influence upon the system. It consists of administering the drug directly to the tumor through arteries that nourish it, i.e. omitting the blood-brain barrier, which should guarantee higher drug concentration in the tumor. There is still the possibility of “immunization” of the lesion to individual drugs while targeting the chemotherapeutic at its goal is significantly facilitated ( in the course of treatment patients are additionally given mannitol, in order to break the blood-brain barrier). At present in the USA and Canada eight clinical trials are running, for which patients with glioblastomas are recruited (including one study directed at child patients).

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Is the method available to patients who do not participate in experimental studies?

The data and experience concerning this method, especially with reference to children, have been gathered for the last few years by the clinic IDOI in Mexico, where it is available to non-participating patients. The activities of the clinic are subject to numerous speculations, which are often spread by people who have never been in direct contact with its staff.

It is not our intention to encourage patients to choose some definite procedure, because – as we have repeatedly pointed out earlier – every decision should result from a conscious decision made by the patient (or their parents), be preceded by thorough analysis and discussed with the doctor in charge. Persons interested in this particular procedure should contact us directly by filling the contact form; we offer to share personal experience as well as detailed information about the treatment itself, the qualification process, the cost, the drug used, and practical aspects of arranging the stay at the center.

As far as adult patients are concerned, we keep gathering information and, in case of questions, offer e-mail contact. More detailed current information, when available, will be put on the website.