Thiotepa
Indications
Thiotepa is used for:
Breast cancer, Ovarian carcinoma, Bladder cancer, Malignant effusions, Condylomata acuminata
Adult Dose
Intravesical
Bladder cancer
Adult: Up to 60 mg instilled in 30-60 mL of sterile water or sodium chloride 0.9% into the bladder of patient previously dehydrated for 8-12 hr and retained for 2 hr. Reposition patient every 15 minutes for max area contact. May be repeated once a wk for up to 4 wk.
For prophylaxis of recurrence after surgical removal of bladder cancer: Up to 60 mg may be instilled at intervals of 1-2 wk, for up to 8 instillations.
Intracavitary
Malignant effusions
Adult: Up to 60 mg in 20-60 mL of sterile water may be instilled after aspiration.
Intravenous
Breast cancer; Ovarian carcinoma
Adult: Dosage must be individualised. Usual range: 0.3-0.4 mg/kg via rapid IV admin every 1-4 wk. Avoid admin if WBC or platelet counts fall below acceptable levels. Stop treatment if WBC falls rapidly.
Hepatic Impairment
Caution; may require lower dose; limit use to cases where benefit outweigh risk
Child Dose
Renal Dose
Renal Impairment
Caution; may require lower dose; limit use to cases where benefit outweigh risk
Administration
IV Preparation
Reconstitute in 1.5 mL SWI to 10 mg/mL which is stable for 8 hr at refrigeration; further dilution in NS, D5W, or LR should be used immediately (within 1 hr of preparation)
IV Administration
Administer over 1 min
Solutions should be filtered through a 0.22 micron filter prior to administration
Contra Indications
Pregnancy; lactation; hypersensitivity; severe myelosuppression with leukocyte count <3000 cells/mm3 or platelet count <150,000 cells/mm3.
Precautions
Elderly; child; preexisting renal, hepatic and bone marrow function impairment. Monitor for fever, chills, sore throat, discoloration of urine, black stools or unusual bleeding or easy bruising. Monitor blood counts before initiation, at least wkly during and at least 3 wk after discontinuation of therapy; monitor hepatic and renal function.
Lactation: not known if excreted in breast milk, do not nurse
Pregnancy-Lactation
Pregnancy Category: D
Lactation: not known if excreted in breast milk, do not nurse
Interactions
Concomitant use of other alkylating agents or irradiation enhance effect. Prolongs action of succinylcholine and other neuromuscular-blocking agents due to inhibition of plasma pseudocholinesterase. Increased risk of myelosuppression when used with colony-stimulating factors (such as filgrastim, lenograstim) 24 hr before to 24 hr after admin of cytotoxic chemotherapy. Coadmin with cyclophosphamide inhibit the metabolism of cyclophosphamide to its active metabolite and decrease both its efficacy and toxicity.
Adverse Effects
Side effects of Thiotepa :
GI disturbances; fatigue, weakness, headache and dizziness; hypersensitivity reactions; blurred vision and conjunctivitis; amenorrhoea, impaired fertility; local irritation, frank chemical or haemorrhagic cystitis; depigmentation of periorbital skin (eye drops).
Potentially Fatal: Bone marrow depression, mutagenesis, teratogenesis and carcinogenesis.
Mechanism of Action
Thiotepa is an ethyleneimine alkylating agent which interferes with DNA replication and transcription of RNA, resulting in the disruption of nucleic acid function. It is also immunosupressive. It may control malignant effusion by a direct antineoplastic effect after intracavitary admin. Low pH enhances reactivity of thiotepa. It has generally been replaced by cyclophosphamide and other drugs.