temozolomide


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temozolomide

 [tem″ah-zo´lah-mīd]
a cytotoxic alkylating agent used as an antineoplastic in the treatment of refractory anaplastic astrocytoma, administered orally.

temozolomide

Temodal, Temodar

Pharmacologic class: Alkylating agent

Therapeutic class: Antineoplastic

Pregnancy risk category D

Action

Rapidly converts to monomethyl triazeno imidazole carboxamide, an active compound that prevents DNA transcription

Availability

Capsules: 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, 250 mg

Injection (powder for solution, lyophilized): 100 mg

Indications and dosages

Refractory anaplastic astrocytoma

Adults: 150 mg/m2 P.O. or by 90-minute I.V. infusion daily for 5 consecutive days of each 28-day treatment cycle. Adjust dosage as appropriate based on absolute neutrophil count.

Newly diagnosed glioblastoma multiforme with radiotherapy

Adults: 75 mg/m2 P.O. or by 90-minute I.V. infusion for 42 days with focal radiotherapy (RT), followed by initial maintenance dose of 150 mg/m2 P.O. or by 90-minute I.V. infusion daily for days 1 to 5 of a 28-day cycle for six cycles. Four weeks after completing the drug plus RT phase, administer drug for an additional six cycles of maintenance treatment. Dosage in maintenance cycle 1 is 150 mg/m2 P.O. or by 90-minute I.V. infusion daily for 5 days, followed by 23 days without treatment. At start of maintenance cycle 2, dosage may be escalated to 200 mg/m2 based on absolute neutrophil and platelet counts. Continue dosage at 200 mg/m2 daily for first 5 days of each subsequent cycle except if toxicity occurs. If dosage wasn't escalated at maintenance cycle 2, escalation shouldn't be done in subsequent cycles.

Dosage adjustment

• Neutropenia, thrombocytopenia

Contraindications

• Hypersensitivity to drug, its components, or dacarbazine

Precautions

Use cautiously in:

• severe hepatic or renal impairment, active infection, decreased bone marrow reserve, other chronic debilitating illness

• elderly patients

• pregnant or breastfeeding patients

• children (safety not established).

Administration

• Follow facility policy for handling and disposing of chemotherapeutic drugs.

• Give capsules whole daily with a full glass of water, consistently either with or without food.

• Bring powder for injection to room temperature before reconstituting with 41 ml sterile water for injection that results in a 2.5-mg/ml solution. Gently swirl but don't shake vials. Don't further dilute reconstituted solution. Use reconstituted solution within 14 hours, including infusion time. Withdraw prescribed dose and transfer into empty 250-ml infusion bag. Give reconstituted solution only by I.V. infusion using infusion pump over 90 minutes. Flush lines before and after each infusion.

• Know that drug may be given in same I.V. line with normal saline solution for injection only.

• Be aware that dosages in 28-day cycle depend on nadir neutrophil and platelet counts.

Adverse reactions

CNS: fatigue, headache, dysphasia, poor coordination, ataxia, anxiety, depression, dizziness, drowsiness, confusion, amnesia, insomnia, mental status changes, weakness, paresis, hemiparesis, paresthesias, seizures

CV: peripheral edema

EENT: abnormal vision, diplopia, pharyngitis, sinusitis

GI: nausea, vomiting, constipation, diarrhea, abdominal pain, anorexia

GU: urinary incontinence or frequency, urinary tract infection, breast pain (in women)

Hematologic: anemia, leukopenia, thrombocytopenia

Metabolic: adrenal hypercorticism

Musculoskeletal: abnormal gait, back pain, myalgia

Respiratory: cough, upper respiratory infection

Skin: pruritus, rash

Other: fever, viral infection, weight gain

Interactions

Drug-drug. Antineoplastics: additive bone marrow depression

Live-virus vaccines: decreased antibody response to vaccine, greater risk of adverse reactions

Valproic acid: decreased oral clearance of temozolomide

Drug-diagnostic tests. Neutrophils, platelets: decreased counts

Drug-food. Any food: reduced rate and extent of temozolomide absorption

Patient monitoring

Monitor CBC with white cell differential. Stay alert for evidence of bone marrow depression.

• Assess neurologic status carefully.

• Monitor fluid intake and output, and weigh patient regularly.

• Be aware that Pneumocystis jiroveci pneumonia prophylaxis is required during concomitant administration of RT and should be continued in patients who develop lymphocytopenia until recovery from lymphocytopenia (circulating tumor cells Grade 1 or less).

Patient teaching

• Tell patient to take capsules consistently with or without food, and with a full glass of water.

• Instruct patient to swallow capsules whole without opening or chewing them and if capsules are accidentally opened or damaged, to avoid inhalation or contact with the skin or mucous membranes.

• If drug causes nausea or vomiting, advise patient to take it 1 hour before or 2 hours after a meal.

• Inform patient that drug may cause abnormal gait and dizziness.

Instruct patient to immediately report unusual bleeding or bruising.

• Advise patient to avoid live-virus vaccines.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration, alertness, and vision.

• Instruct patient to report suspected pregnancy. Caution her not to breastfeed.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

temozolomide

Temodal® Oncology An alkylating agent used for recurrent gliomas–eg, anaplastic astrocytoma, and possibly melanoma and other solid tumors. See Astrocytoma, Glioblastoma multiforme.
References in periodicals archive ?
Contract notice: successive supply of carboplatin, doxorubicin, citarabine, bendamustine, capecitabine and temozolomide, destined to the organizational structures of integrated management of the galician health service
This recently-approved arm of the study will enroll up to 24 newly-diagnosed patients who have undergone surgery and chemoradiation with temozolomide - TMZ - but will now receive VAL-083 in place of standard of care TMZ for adjuvant therapy.
The phase three CheckMate -498 trial evaluating Opdivo plus radiation against temozolomide plus radiation in patients with newly diagnosed O6-methylguanine-DNA methyltransferase (MGMT)-unmethylated glioblastoma multiforme (GBM) did not achieve its overall survival at final analysis.
However, grade 3 and 4 toxicities were noted with PCV therapy and a conclusive replacement with temozolomide was unab le to be ascertained.
Currently, standard of care for the disease includes surgery and postoperative radiation therapy with concurrent and adjuvant chemotherapy using temozolomide.
Surgery followed by fractionated radiation therapy with concomitant and adjuvant temozolomide would be most frequently used.
CRUK scientists led the development of temozolomide. From drug development to the first clinical trials of the drug in people with cancer, their researchers were involved every step of way.
Combination of capecitabine and temozolomide (CAPTEM) is one of the chemotherapeutic options for progressive metastatic gastroenteropancreatic neuroendocrine tumors.
First, temozolomide has been the most common agent chosen as a systemic therapy regimen because it is believed to penetrate the blood-brain barrier.[18] Moreover, its radiosensitive effect and relatively lower toxicity have made it an ideal systemic therapy regimen, especially when administered concomitantly with WBRT.[19] However, with the exception of glioma, temozolomide is not the standard systemic therapy regimen used for most solid tumors.
A letter written by FID Karachi said that the cancer patients are compelled to buy Temoside (temozolomide) 100mg Capsules at Rs31000 while its import price is Rs7225 (USD 58.57).