STREPTOZOCIN

STREPTOZOCIN
(strep-toe-zoe'sin)
Zanosar
Classifications: antineoplastic; alkylating agent;
Therapeutic: antineoplastic

Prototype: Cyclophosphamide
Pregnancy Category: D

Availability

1 g injection

Action

Streptozocin is highly toxic and has a low therapeutic index; thus a clinically effective response is likely to be accompanied by some evidence of toxicity. Inhibits DNA synthesis in cells and prevents progression of cells into mitosis, affecting all phases of the cell cycle (cell-cycle nonspecific). Appears to have minimal effects on RNA or protein synthesis.

Therapeutic Effect

Successful therapy with streptozocin (alone or in combination) produces a biochemical response evidenced by decreased secretion of hormones as well as measurable tumor regression. Thus, serial fasting insulin levels during treatment indicate response to this drug.

Uses

Metastatic functional and nonfunctional islet cell carcinoma of pancreas, as single agent or in combination with fluorouracil.

Unlabeled Uses

A variety of other malignant neoplasms including metastatic carcinoid tumor or carcinoid syndrome, refractory advanced Hodgkin's disease, and metastatic colorectal cancer.

Contraindications

Pregnancy (category D), lactation. Safety in children is not established.

Cautious Use

Renal impairment; hepatic disease, hepatic impairment; patients with history of hypoglycemia; diabetes mellitus.

Route & Dosage

Islet Cell Carcinoma of Pancreas
Adult: IV 500 mg/m2/d for 5 consecutive days q6wk or 1 g/m2/wk for 2 wk, then increase to 1.5 g/m2/wk, infuse dose over 15 min to 6 h

Renal Impairment
If Clcr 10–50 mL/min, use 75% of dose; if less, use 50% of dose.

Administration

Intravenous
  • Use only under constant supervision by physician experienced in therapy with cytotoxic agents and only when the benefit to risk ratio is fully and thoroughly understood by patient and family.
  • Wear gloves to protect against topical exposure, which may pose a carcinogen hazard, when handling streptozocin. If solution or powder comes in contact with skin or mucosa, promptly flush the area thoroughly with soap and water.

PREPARE: IV Infusion: Reconstitute with 9.5 mL D5W or NS, to yield 100 mg/mL. Solution will be pale gold. May be further diluted with up to 250 mL of the original diluent. Protect reconstituted solution and vials of drug from light.  

ADMINISTER: IV Infusion: Give over 15–60 min. Inspect injection site frequently for signs of extravasation (patient complaints of stinging or burning at site, swelling around site, no blood return or questionable blood return). If extravasation occurs, area requires immediate attention to prevent necrosis. Remove needle, apply ice, and contact physician regarding further treatment to infiltrated tissue.  

INCOMPATIBILITIES Y-site: Allopurinol, aztreonam, cefepime, piperacillin/tazobactam.

  • Note: An antiemetic given routinely every 4 or 6 h and prophylactically 30 min before a treatment may provide sufficient control to maintain the treatment regimen (even if it reduces but not completely eliminates nausea and vomiting).
  • Discard reconstituted solutions after 12 h (contains no preservative and not intended for multidose use).

Adverse Effects (≥1%)

CNS: Confusion, lethargy, depression. GI: Nausea, vomiting, diarrhea, transient increase in AST, ALT, or alkaline phosphatase; hypoalbuminemia. Hematologic: Mild to moderate myelosuppression (leukopenia, thrombocytopenia, anemia). Metabolic: Glucose tolerance abnormalities (moderate and reversible); glycosuria without hyperglycemia, insulin shock (rare). Urogenital: Nephrotoxicity: azotemia, anuria, proteinuria, hypophosphatemia, hyperchloremia; Fanconi-like syndrome (proximal renal tubular reabsorption defects, alkaline pH of urine, glucosuria, acetonuria, aminoaciduria): Hypokalemia, hypocalcemia. Other: Local necrosis following extravasation.

Interactions

Drug: myelosuppressive agents add to hematologic toxicity; nephrotoxic agents (e.g., aminoglycosides, vancomycin, amphotericin B, cisplatin) increase risk of nephrotoxicity; phenytoin may reduce cytotoxic effect on pancreatic beta cells.

Pharmacokinetics

Absorption: Undetectable in plasma within 3 h. Distribution: Metabolite enters CSF. Metabolism: In liver and kidneys. Elimination: 70–80% of dose in urine, 1% in feces, and 5% in expired air. Half-Life: 35–40 min.

Nursing Implications

Assessment & Drug Effects

  • Lab tests: Perform CBC at least weekly, and liver function tests prior to each course of therapy. Dosage adjustment or discontinuation may be required if there is evidence of decreased liver or bone marrow function. Obtain serial urinalyses and determinations of BUN, creatinine clearance, and serum electrolytes prior to and weekly during therapy, then for 4 wk after termination of therapy.
  • Ensure that repeat courses of streptozocin treatment are not given until patient's liver, kidney, and hematologic functions are within acceptable limits. Platelet and leukocyte nadirs generally occur 1–2 wk after beginning therapy.
  • Report evidence of drug-induced declining kidney function promptly; changes are dose related and cumulative.
  • Be alert to early laboratory evidence of kidney dysfunction: Hypophosphatemia, mild proteinuria, and changes in I&O ratio and pattern.
  • Mild adverse renal effects may be reversible following discontinuation of streptozocin, but nephrotoxicity may be irreversible, severe, or fatal.
  • Be alert to symptoms of sepsis and superinfections (leukopenia) or increased tendency to bleed (thrombocytopenia). Myelosuppression is severe in 10–20% of patients and may be cumulative and more severe if patient has had prior exposure to radiation or to other antineoplastics.
  • Monitor for S&S of superinfection (see Appendix F).
  • Monitor and record temperature pattern to promptly recognize impending sepsis.

Patient & Family Education

  • Inspect site at weekly intervals and report changes in tissue appearance if extravasation occurred during IV infusion.
  • Report symptoms of hypoglycemia (see Appendix F) even though this drug has minimal, if any, diabetogenic action.
  • Drink fluids liberally (2000–3000 mL/d). Hydration may protect against drug toxicity effects.
  • Report S&S of nephrotoxicity (see Appendix F).
  • Do not take aspirin without consulting physician.
  • Report to physician promptly any signs of bleeding: Hematuria, epistaxis, ecchymoses, petechial.
  • Report symptoms that suggest anemia: Shortness of breath, pale mucous membranes and nail beds, exhaustion, rapid pulse.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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