Brain Chemotherapy (Continue...)|
Excerpt from The Latest Treatments in Adult Care: Medical Therapies
When we make recommendations for chemotherapy, the recommendations again are very individual and they're based on a number of factors, including the type of tumor, most importantly, the grade of the tumor, the age of the patient, the stage of the disease and the medical condition or something we call the performance status of patients. How well are they going to be able to tolerate the chemotherapy without excessive side-effects?
These are vast generalizations, but the kinds of characteristics that tend to make us recommend chemotherapy relative to patient characteristics are young patients, healthy patients, or patients who are in otherwise good medical condition. The kinds of tumors where we're more likely to recommend chemotherapy for are the high-grade tumors as opposed to low-grade ones, tumors that fall into the group known as oligodendroglioma, medulloblastomas, and lymphomas. But again, these are vast generalizations and the decision to use chemotherapy or not is individual.
The kinds of drugs that we use are a bit of an alphabet soup. The standard drugs we've used for years are a group of drugs known as nitrosoureas, BCNU, CCNU, procarbazine, vincristine, carboplatin, and methotrexate again, depending on the type of tumor. There are some newer drugs out there, including timazolamide, a new drug that's just been approved by the FDA for use in gliomas and is an effective drug. And drugs that are less effective or for whom their real use is still being defined, include Tamoxifen, CPT-11, and Gliadel wafers.
Timadar, which has also been called Timadol and the generic name is timazolamide, is an FDA-approved drug. It's approved specifically for the treatment of patients who have what are known as anaplastic astrocytomas whose tumors have returned following standard treatment, being defined as plus-minus surgery and radiation therapy. The results of the major trials that have been done have shown that approximately a third of those patients treated with timazolimide or Timadol will have tumor shrinkage, with another about 20 percent of patients having stabilization of their tumor for a period of time. The data for patients with more malignant gliomas like glioblastomas are not as encouraging. So the upshot is that timazolimide is another bullet in our armamentum. It's not a miracle drug, to say the least. But given the paucity of drugs that we have, particularly for malignant gliomas, another bullet is welcome.
The idea of high-dose chemotherapy is based on the rather simplistic idea that more the better. The reason that chemotherapy doesn't work so well is that you can't give enough of it, because if you try to go to the highest doses possible the side-effects will be so severe that you'll kill the patient before you reach a dose that will kill the tumor. And the major dose-limiting toxicity of chemotherapy is the effect on the bone marrow and the blood counts. So the idea comes out that if you can take out some of the blood cells, and actually the mother cells, the progenitor cells, from the patient before you give them the chemotherapy, you then give them these otherwise lethal doses of chemotherapy. Let the chemotherapy circulate through the body, attack the tumor, leave the body and then give back the progenitor cells to the patient after the chemotherapy is out of their body. Basically, by protecting the bone marrow stem cells, you can give patients much higher doses of chemotherapy. The fact is you can do that; it's done routinely for diseases like leukemia and lymphoma.
The problem is that the only place where high-dose chemotherapy has ever been shown to truly be effective is in extremely chemotherapy-sensitive tumors like leukemia. In diseases that are generally relatively chemotherapy-resistant, like most solid tumors such as gliomas, the chances of high-dose chemotherapy really making a difference and certainly being worth the toxicity in my opinion are extraordinarily low. Now there is an exception to that in the brain tumor world, and that's a tumor known as a medulloblastoma, again much more common in children than in adults. This is an extraordinarily chemotherapy-sensitive tumor, so there well may be a role, and I actually believe there is a role in certain situations for people with medulloblastomas for high-dose chemotherapy and bone marrow transplant.
But I think it's still important to say that as useful as those drugs that we just talked about can be for some patients, they're not optimal and they aren't curative in the majority of patients with the majority of tumors. So we need to find other therapies and that's where experimental therapeutics come into play.