Intravenous Neuroendocrine tumours of pancreatic origin
Adult: Treatment in patients with metastatic islet cell carcinoma of the pancreas (progressive or symptomatic): Alone or in combination with other antineoplastic agents: Daily regimen: 500 mg/m2 once daily for 5 consecutive days every 6 weeks until disease progression or unacceptable toxicity occurs. Dose escalation is not recommended. Weekly regimen: Initially, 1,000 mg/m2 once weekly for the 1st 2 weeks, then may escalate subsequent dose according to patient’s therapeutic response and tolerability up to Max single dose of 1,500 mg/m2. Alternative dosing regimen: Three-weekly regimen: 500 mg/m2 daily for 5 consecutive days during cycle 1, then 1,000 mg/m2 every 3rd week during the subsequent cycles. Doses may be given via IV inj or infusion over 30 minutes to 4 hours. Premedication with antiemetics is recommended. Dosage and treatment protocol recommendations may vary among individual products and between countries (refer to detailed product guideline). Elderly: Initiate at the lower end of the dosing range.
eGFR ≤30 mL/min/1.73 m2: Contraindicated. eGFR >30-≤45 mL/min/1.73 m2: Evaluate the benefit/risk ratio. eGFR >45-≤60 mL/min/1.73 m2: Reduce dose by 50%. Dosage recommendations may vary among individual products and between countries (refer to detailed product guideline).
Dose reduction may be required.
Reconstitute vial labelled as containing 1 g with 9.5 mL of 0.9% NaCl solution for inj or dextrose 5% in water to achieve a concentration of 100 mg/mL. If more dilute infusion solutions are desirable, may further dilute the reconstituted solution in the same vehicles.
Renal impairment (eGFR ≤30 mL/min/1.73 m2). Concomitant use with other potentially nephrotoxic drugs, or live and live-attenuated vaccines.
Patient with pre-existing renal disease and diabetes. Provide adequate hydration before administration to help reduce the risk of nephrotoxicity. Avoid extravasation. Renal (eGFR >30-≤60 mL/min/1.73 m2) and hepatic impairment. Elderly. Pregnancy and lactation.
Significant: Severe nausea and vomiting; hepatotoxicity (e.g. hypoalbuminaemia, elevated transaminases and lactate dehydrogenase), mild to moderate glucose intolerance (reversible); CNS effects (e.g. lethargy, confusion); severe tissue lesions and necrosis (following extravasation). Rarely, mild bone marrow suppression (e.g. mild anaemia or haematocrit reduction). Gastrointestinal disorders: Diarrhoea. General disorders and administration site conditions: Inj site reactions (e.g. burning sensation, erythema, oedema, tenderness), fever. Psychiatric disorders: Depression. Renal and urinary disorders: Urinary disorders, nephrogenic diabetes insipidus. Potentially Fatal: Dose-related and cumulative renal toxicity (e.g. proteinuria, hypophosphataemia, anuria, glycosuria, renal tubular acidosis). Rarely, severe haematological toxicity (e.g. substantially decreased leucocyte and platelet count).
This drug may cause confusion or lethargy, if affected, do not drive or operate machinery.
Monitor renal function (including BUN, serum creatinine, serial urinalysis, creatinine clearance or eGFR) and serum electrolytes at baseline, weekly during and for 4 weeks following therapy; LFTs and CBC with differential and platelets weekly. Obtain 24-hour urine collection if proteinuria is detected on urinalysis. Closely monitor infusion site to prevent extravasation, and glucose levels (in patients with diabetes).
Increased immunosuppression with risk of lymphoproliferative disorders with immunosuppressive drugs. May prolong the elimination half-life of doxorubicin and result in severe bone marrow suppression; consider doxorubicin dose reduction when used concurrently with streptozocin. Phenytoin may reduce the cytotoxic effect of streptozocin. Coadministration with carmustine may synergistically increase the haematological toxicity of both drugs. Potentially Fatal: May cause severe cumulative renal toxicity when given concurrently with other potentially nephrotoxic agents. May increase the risk of severe infections with live and live-attenuated vaccines.
Description: Streptozocin is an antineoplastic antibiotic nitrosourea. Its exact mechanism has not been fully established; however, it has been shown to undergo spontaneous decomposition to produce reactive methylcarbonium ions that inhibit deoxyribonucleic acid (DNA) synthesis by alkylation and cross-linking of DNA strands, and possibly by protein modification. Although it inhibits the progression of cells into mitosis, no specific cell cycle phase is particularly sensitive to its lethal effects. Onset: Therapeutic response: Approx 17 days (1,500 mg/m2 once weekly regimen). Pharmacokinetics: Distribution: Distributed to body tissues, specifically in the liver, kidneys, pancreas, and intestines. Metabolism: Extensively and rapidly metabolised, primarily in the liver and possibly in the kidneys. Excretion: Via urine (approx 60-70%; 30% as nitrosourea containing metabolites, 10-20% as unchanged drug); faeces (<1%). Elimination half-life: <1 hour.
Store intact vials between 2-8°C. Protect from light. Reconstituted solution must be used within 12 hours. Storage recommendations may vary among individual products or between countries (refer to product-specific guidelines). This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
L01AD04 - streptozocin ; Belongs to the class of alkylating agents, nitrosoureas. Used in the treatment of cancer.
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