thiotepa; thiophosphamide (Tespa, Thioplex)

Introduction

Tradenames: Tespa, Thioplex.

Indications

• adenocarcinoma of the breast & ovary
  • breast cancer, ovarian cancer
• chronic lymphocytic leukemia
• Hodgkin's lymphoma
• non-Hodkin's lymphoma
• malignant effusions
  • ascites
• carcinoma of the bladder

Contraindications

• severe myelosuppression
• pre-exsisting hepatic, renal or bone marrow damage

pregnancy category = d

Dosage

• IV: 12-16 mg/m2 every 1-4 weeks
• intravesicular: 30-60 mg every 4 weeks
• intrathecal: 1-10 mg/m2 once to twice weekly

Powder for injection: 15 mg. (1 mg/mL is isotonic)

Pharmacokinetics

• extensively metabolized by the liver
• 1/2life 2-3 hours from plasma
• 1/2life 6-9 hours from CSF after intrathecal administration

elimination via liver

1/2life = 2-3 hours

Adverse effects

• common (> 10%)
  • myelosuppression
    • dose-limting toxicity
    • severe thrombocytopenia (cumulative & dose-related)
    • moderate to severe leukopenia
    • pancytopenia may be fatal
    • onset 7-10 days
    • nadir 14 days
    • recovery 28 days
  • pain at site of injection
• less common (1-10%)
  • hyperuricemia, dizziness, fever, headache, alopecia, rash, pruritus, stomatitis, hematuria, nausea/vomiting*
• uncommon (< 1%)
  • alopecia, rash, dizziness, fever, tightness of the throat, anorexia, allergic reactions, hemorrhagic cystitis
• other
  • mild nausea* (emetic potential is low)
  • phlebitis
  • dysuria
  • cystitis (rare)
  • cognitive impairment (cumulative dose-related)
  • secondary carcinogenesis

• drug adverse effects of alkylating agents

Drug interactions

• succinylcholine: increased apnea with concurrent administration
• other alkylating agents & radiation therapy intensifies toxicity rather than enhances therapeutic benefits

Test interactions

increases serum K+

Mechanism of action

• alkylating agent
• interferes with DNA base-pairing

More general terms

• alkylating agent

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5453