The group of so called 'alkylating agents' targets the genetic information of the tumor cell, the DNA.
Temozolomide is a relatively new chemotherapy drug. It is given by mouth, usually as a combination of pills of different strengths. Temodar® comes in four different strengths [250 mg, 100 mg, 20 mg, 5 mg]. Each chemotherapy cycle with Temodar lasts 4 weeks. The treatment is given on the first five days followed by a resting period of 23 days. Other schedules exist such as daily low-dose temozolomide during radiation therapy for malignant gliomas.
The most common side effects are fatigue, mostly during the days of drug treatment, nausea and a drop in white blood cells and blood platelets. Blood draws are required on day #21 and day #28 of each cycle or weekly if you receive temozolomide daily during radiation.
Zofran in combination with Temodar can make you constipated. It is advised to take an over the counter laxative such as Senna prophylactically.
PCV (Combination chemotherapy with procarbazine, lomustine (CCNU) and vincristine PCV is commonly used in oligodendrogliomas and oligoastrocytomas. Procarbazine and lomustine [CCNU] are 'alkylating' agents attacking the DNA of tumor cells whereas vincristine is a 'spindle toxin' that inhibits proteins that are essential for cell division.
Procarbazine is given by mouth. Tablet strength is 50 mg. You will be prescribed to take two or three tablets on day #8 to #21. Procarabazine can cause sterility. Male patients should ask their doctor about the possibility of storing a sperm specimen in the Yale Sperm Bank.
Procarbazine, an inhibitor of monoamine oxidase, cannot be used concomitantly with certain antidepressants or tyramine-rich food or alcohol.
As a general rule, you should always notify your doctor if you need any type of medication (including any over the counter medication!) while on procarbazine, five days before it is started and five days after the end of the two week period of drug administration.
Lomustine [CCNU] is given by mouth on day one. It comes in capsules of different strengths. You will likely take a combination of pills. The most common side effects are a drop in blood cell counts, and nausea/vomiting.
Vincristine is given as an injection or short infusion on day #8 and day #28. You will see your doctor and have blood drawn prior to each administration. You should always plan to have somebody drive you to your appointment. Acute side effects are rare (abdominal discomfort) but could potentially interfere with your ability to drive.
Carmustine [BCNU] has a similar mechanism of action as lomustine. Both drugs have represented the major chemotherapy agents provided for malignant glioma. It is usually given as an intravenous infusion every six weeks. BCNU is toxic to bone marrow precursors of blood cells, lung, liver and kidney. BCNU is the chemotherapeutic agent used in implantable wafers [Gliade®].
Cyclophosphamide can be administered by vein or by mouth. It is used for the treatment of systemic lymphoma and primitive neuroektodermal tumors (see Introduction to Brain Tumors).
Methotrexate is a potent inhibitor of dihydrofolate reductase (DHFR), an enzyme that catalyzes the synthesis of carrier molecules needed for the synthesis of nucleic acids (the molecules that form the DNA, the genetic information). It is used in the treatment of primary brain lymphoma and primary sarcomas of the nervous system.
Molecules analogous to nucleic acids - the molecules that form the DNA - interfere with the replication of DNA, a step that is indispensable for cell proliferation. Cytosine arabinoside (Ara-C) is a commonly used agent belonging to this group of agents. It is given into a vein or directly into the spinal fluid for lymphoma of the nervous system.
Division of tumor cells can be inhibited by Vinca alkaloids (e.g., vincristine). They are naturally found in Catharanthus roseus. Vinca alkaloids are administered by intravenous injection or short infusion for patients with gliomas or primitive neuroektodermal tumors.
Compounds based on elemental platinum
Platinum compounds (cisplatin, carboplatin, oxaliplatin) bind to DNA and thus inhibit DNA reduplication and cell proliferation. They are used for the treatment of glioma, medulloblastoma, primitive neuroektodermal tumor and germ cell tumors.
DNA, the chemical basis of genetic information, is a dynamic molecule that coils and bends within the nucleus of each cell. These coils and bends must be temporarily unwound in order for the tumor cell to be able to replicate the genetic information and then divide. This process is facilitated by enzymes called topoisomerase I and II. Pharmacological inhibition of these enzymes can be used to treat cancer of the brain. Drugs that inhibit topoisomerases were found in plant extracts. The ones in use today mostly are derivatives of the original compounds chemically modified to increase their efficacy and decrease toxicity.
Irinotecan is a semisynthetic derivative of camptothecin, an alkaloid extract from certain plants. Various dosing schedules exist. Most commonly, irinotecan is given every three weeks as an intravenous infusion or once every week for four weeks followed by a break of two weeks. It is used for the treatment of malignant gliomas.
Etoposide is a semisynthetic derivative of podophyllotoxin, a substance found in mayapple extracts. It is being used as part of multi-drug regimens against a large number of primary brain tumors. It is given as an infusion several days in a row followed by two to three weeks rest or daily as a tablet.