
<b> Temozolomide -- Trade Names: Temodal, Temodar.</b> 
Manurfacturer is Schering, and Temodar Oral Capsules come in doses 5 mg, 20mg, 100mg, 250mg

Temozolomide has FDA approval for use in the treatment of refractory relapsed astrocytoma in adults. It is being studied in clinical trials and used off-label for treatment of some resistant cancers, uterine LMS being one of them. It has considerable efficacy for uterine LMS, according to some early results from ACOR LMS LIST people who are in the clinical trials, but may not be so effective against other LMS. The response rate of Advanced Soft Tissue Sarcomas to Temozolomide at high dosage [750 to 1000 mg/m2] was not so good, at approximately 3%, one partial response out of 31 subjects. However, uterine leiomyosarcomas did show responses in more than one trial.  And chemosensitivity testing [see Testing Your Tumor in the Approach to Treatment section of this website] certainly will help decide whether to try this drug.

Temozolomide does cross the blood brain barrier, and is being used with some brain tumors.

Safety and efficacy is not established in children. Clearance and half-life of temozolomide was similar in children 3--17 years of age and adults. Experience in those 65 years of age and older is insufficient to determine whether they respond differently than younger adults. Caution is advised. 

<b>Pharmacology & Chemistry </b>
Temozolomide, an imidazotetrazine derivative, is an antineoplastic agent. Temozolomide is a prodrug and has little, if any, pharmacologic activity until hydrolyzed [broken apart] in the body to MTIC [5-(3-methyltriazen-1-yl)imidazole-4- carboxamide]. Following administration of temozolomide, the drug undergoes rapid, nonenzymatic hydrolysis at physiologic [normal body] pH to MTIC. MTIC is thought to exert its cytotoxic effects by acting as an alkylating agent at the O6 and N7 positions of guanine in DNA, thereby damaging DNA.
Cytochrome P-450 isoenzymes play only a minor role in temozolomide and MTIC metabolism. 

<b>How It is Used:</b>
for example, in Astrocytoma-- a brain tumor --
The initial dosage of temozolomide for the treatment of refractory anaplastic astrocytoma in adults is 150 mg/m2 daily for 5 consecutive days of a 28-day treatment cycle. 

Subsequent dosage is adjusted based on the lowest level [nadir] of platelet and absolute neutrophil counts (ANC) during the previous cycle and on ANC and platelet counts on day 29 (i.e., day 1 of the next cycle). A complete blood cell count (CBC) should be obtained on day 22 (i.e., 21 days after the first dose) of the cycle [or within 48 hours of that day] and weekly until the ANC and platelet counts exceed 1500 and 100,000/mm3, respectively. The next cycle should be withheld until these counts are exceeded. If both nadir and day-of-dosing ANC and platelet counts exceed 1500 and 100,000/mm3, respectively, then temozolomide dosage may be increased to 200 mg/m2 daily for 5 consecutive days of the next 28-day cycle. If either the ANC is between 1000--1500/mm3 or the platelet count is between 50,000--100,000/mm3 during any cycle, therapy should be postponed until the ANC and platelet counts exceed 1500 and 100,000/mm3, respectively, at which time a dosage of 150 mg/m2 daily for 5 consecutive days should be used. If either the ANC or platelet count declines to less than 1000 or 50,000/mm3, respectively, during any cycle, dosage for the next cycle should be reduced by 50 mg/m2 daily, but not to less than the lowest recommended dosage of 100 mg/m2 daily. 
Temozolomide therapy can be continued until disease progression occurs. Although therapy was continued for up to 2 years in the clinical study establishing efficacy, the optimum duration is not known. 

<b>How to Take Temozolomide:</b>
Temozolomide is available in capsule form, and is taken by mouth. The capsules should be swallowed whole with a FULL glass of water and taken at the same time every day, on an empty stomach (one hour before or three hours after a meal) or at bedtime, unless otherwise directed by your doctor.  Dosage is based on your size and response to therapy. Although the drug may be administered with food, administration on an empty stomach may reduce the incidence of nausea and vomiting. Food may decrease the rate and extent of absorption of temozolomide, so the drug should be administered in a consistent manner relative to food intake.  People on temozolomide do not have nausea IF they take their Kytril or Zofran exactly on schedule.  If they stop taking these antiemetics, they then will have nausea requiring an IV [in several cases].  Don't prove it to yourself that the Kytril or Zofran is necessary.

Take Temozolomide by mouth, generally once daily for five consecutive days per 28-day treatment cycle; or take as directed by your doctor. Do not crush or chew the capsules. If you vomit within 30 minutes of taking this medication, notify your doctor immediately. If you vomit before taking this medication, your doctor may be able to prescribe anti-nausea medication for you to take before therapy begins. Do not open the capsules (medication). If capsules are accidentally opened or damaged, avoid inhalation or contact of the medication with skin or mucous membranes (e.g., inside the nose). The need for precautions to avoid exposure to capsule contents is because of carcinogen potential. Take all other medication (e.g., anti-nausea drugs) exactly as prescribed by your doctor. 

To minimize the risk dosing mistakes, the manufacturer recommends that each daily dose of temozolomide be packaged separately and labeled as day 1, day 2, day 3, day 4, and day 5 and that patients be advised to take all the capsules in a single package as the single dose for that day of the cycle. 
Keep the capsules in a safe place away from children. If your doctor decides to stop treatment, return any remaining capsules to the pharmacist. DO NOT flush them down the toilet or throw them away. 


<b>DIfferent Schedules of Administration:</b>

Temozolomide taken 150-200 mg/m2 daily for 5 consecutive days, repeated every 28 days.

Temozolomide administered at a dose of 75 mg/m2/day, as a 6-week oral continuous schedule every 9 weeks.

Temozolomide 1,000 mg/m2 equally split into 5 doses over a 16 hr period every 28 days [200mg/m2 every 4 hours for 5 dose total.] Myelosuppression precludes this schedule's wider application, but MGMT [AGAT] levels in Peripheral Bone Marrow Cells predicted the dose intensity of temozolomide that patients could sustain, suggesting a means by which individuals suitable for this approach might be identified.

Temozolomide 360 mg/day for 5 days continuously out of every 7 days, experimental schedule in an ongoing trial.


<b>Contraindications:</b>
Warning: Do not use if you are pregnant, plan to become pregnant or while breastfeeding. Pregnancy should be avoided during therapy. If used during pregnancy, the fetus or embryo may be severely damaged.
For severe chronic neutropenia or thrombocytopenia, action to reduce the risk of adverse interaction is usually required, as temozolomide will make these 
conditions worse. 

It must be used with caution in patients with severe hepatic or renal impairment. Pharmacokinetics in patients with mild to moderate hepatic impairment is similar to those in patients with normal hepatic function. Drug clearance is not affected by renal function in patients with creatinine clearances of 36 to 130 mL/minute per m2. 
If you have known hypersensitivity to temozolomide or any ingredient in the formulation, or have known hypersensitivity to dacarbazine (DTIC), since both drugs are metabolized to MTIC. 

<b>Possible side effects: </b>
<b>Bone Marrow Suppression. </b>This can result in anemia, risk of bruising or bleeding, and infection. Your blood count will be monitored. This effect is not immediate, and the low points occur at about 26 to 28 days after treatment cycle. It usually develops during the first few cycles of treatment, and resolves within 14 days. If it is severe, hospitalization, transfusion, and/or holding back the temozolomide may be done. Low platelet and white cell counts are the dose limiting toxicities for temozolomide. There is more frequent incidence of these complications in women and geriatric patients. Your blood count will be checked regularly.

If your temperature goes above 38°C (100.5°F) or if you develop any unexplained bruising or bleeding, or suddenly feel unwell, even with a normal temperature, contact your doctor or the hospital straight away. 
Nausea and Vomiting were severe in 10% and 6%. These are controlled with anti-nausea drugs that must be taken before you take the Temodar. Your doctor will prescribe them.

<b>Diarrhea.</b> This can usually be controlled with medication. Drink plenty of fluids if you do get diarrhea. Let your doctor know if it is severe or carries on for more than a few days.

<b>Constipation</b>. Drink plenty of fluids, eating a high fiber diet and take gentle exercise. Sometimes you may need to take laxatives.

<b>Appetite Loss.</b> Strange Taste. A dietician or specialist nurse at your hospital can give advice. It is important that you eat well and maintain your weight.

<b>Skin and Hair</b> Rashes. Possibly itchy. Call your doctor's attention to it, and treatment can be prescribed.  Hair loss. Hair may thin, or occasionally be lost completely. If it happens, it starts 3-4 weeks after starting treatment and is temporary.

<b>Headache or Dizziness or Shortness of Breath. Let your doctor know.</b>

<b>Tiredness or Weakness</b>. Allow yourself plenty of time to rest. 

<b>Fever and Chills.</b> Your doctor may prescribe tablets to reduce this side effect, which doesn't last long.  This is a serious problem if it occurs when your white cell counts are very low.

<b>Fertility.</b> Your ability to conceive or father a child may be affected by taking this drug. You may wish to discuss fertility with your doctor before starting treatment. 

<b>Contraception.</b> It is not advisable to become pregnant or father a child while taking temozolomide as it may harm the developing foetus. However, do not use oral contraceptives ("the pill") without checking with your doctor. If you are pregnant, breast feeding or planning children in the future, inform your doctor of this before treatment. Many chemotherapy drugs can cause sterility. 


<b>Before You Start Treatment:
Tell your doctor if you have any of the following medical problems:</b>

chickenpox or exposure to chickenpox 
gout
heart disease
congestive heart failure
shingles
kidney stones or disease
liver disease, blood disorders
allergies (especially to dacarbazine)

Never begin taking a new medication, prescription or nonprescription, without asking your doctor or nurse if it will interact with alcohol, foods or other medications, including vitamins or herbals. Some drug products can cause drowsiness and may affect activities such as driving.

<b>PRECAUTIONS:</b> 

	* This medication can lower the body's ability to fight an infection. Notify your doctor promptly if you develop any signs of an infection such as fever, chills or persistent sore throat. 
	* Use this medication with caution in the elderly because they may be more sensitive to the effects of the drug. Use this medication with caution in women because they may be more sensitive to the effects of the drug. 
	* This medication is not recommended for use during pregnancy. Consult your doctor for more details. Men and women should use effective birth control while using this medication. 
	* It is not known if this drug passes into breast milk. Due to the potential risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast- feeding. 
	* Consult your doctor or pharmacist for more information. 

<b>DRUG INTERACTIONS:</b> Tell your doctor of all prescription and nonprescription medication you may use. Do not start or stop any medicine without doctor or pharmacist approval. 

<b>OVERDOSE:</b> If overdose is suspected, contact your local poison control center or emergency room immediately. 

<b>Do not share this medication with others. </b>Laboratory and/or medical tests (e.g., blood tests, brain scans) may be performed to monitor your progress. Keep all scheduled medical appointments. 

<b>MISSED DOSE:</b> If you miss a dose, contact your doctor or healthcare provider immediately to establish a new dosing schedule. 
STORAGE: Store at room temperature below 77 degrees F (25 degrees C) away from light and moisture.

<b> It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity. </b>
