topotecan (Hycamtin, SKF-104864A, Topo, TPT)

Introduction

Tradename: Hycamtin.

Indications

• treatment of metastatic ovarian cancer
  • after failure of initial therapy
• treatment of recurrent & stage IVB cervical cancer in combination with cisplatin
  • ONLY if patient has NOT previously received cisplatin (NGC NICE)
• relapsed small-cell lung cancer
  • oral topotecan, IV not recommmended
• Ewing sarcoma
• osteosarcoma

Contraindications

• pregnant or breast-feeding women
• severe bone marrow suppression Lyophilized powder:
• store at room temperature & protect from light
• reconstitute with 4 mL sterile water for injection (SWI)
• further dilute in 100 mL D5W
• 2.5 mg/mL + 50 mg of mannitol, pH = 3.5 when reconstituted with 2 mL sterile water for injection (SWI)
• 4 mg base/vial (as HCl)

pregnancy category = d

Monitor

• complete blood count (CBC)
• renal function tests

Adverse effects

• common (> 10%)
  • headache, alopecia (reversible), nausea/vomiting, diarrhea, myelosuppression
• less common (1-10%)
  • paresthesia, dyspnea
• uncommon (< 1%)
  • mild erythema & bruising
• other
  • emetic potential is moderately low (10-30%)
  • myelosuppression
    • dose-limiting toxicity
    • WBC mild to severe, platelets mild at low doses
    • nadir 8-11 days
    • recovery 14-21 days
  • may cause permanent sterility

Drug interactions

• increased toxicity with filgastim (G-CSF)
• coadministration with other antineoplastic agents is associated with increased morbidity & mortality (i.e. cisplatin)

Laboratory

• topotecan in serum/plasma

Mechanism of action

• inhibits topoisomerase-1

More general terms

• topoisomerase-1 inhibitor

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=60700
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=438007
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5515
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=60699
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=438006