Thiotepa
Mechanism :
Thiotepa is a cytotoxic agent of the polyfunctional type, related chemically and pharmacologically to nitrogen mustard. The radiomimetic action of thiotepa is believed to occur through the release of ethylenimine radicals which, like irradiation, disrupt the bonds of DNA.
Indication :
- Sarcomas
- Haematopoietic stem cell transplantation conditioning
- Autologous HPCT for solid tumors, CNS tumors and allogenic HPCT for haematological diseases
Contraindications :
Thiotepa is contraindicated in patients with a known hypersensitivity to this preparation. Therapy is probably contraindicated in cases of existing hepatic, renal, or bone-marrow damage. However, if the need outweighs the risk in such patients, thiotepa may be used in low dosage, and accompanied by hepatic, renal and hemopoietic function tests.
Dosing :
Autologous HPCT in Solid tumours, CNS tumors:
150 mg/m²/day (6 mg/kg/day) to 350 mg/m²/day (14 mg/kg/day) as a single daily infusion, for 2-3 consecutive days; Max cumulative dose: 1050 mg/m² (42 mg/kg).
Allogeneic HPCT in Haematological diseases, Refractory cytopenia:
125 mg/m²/day (5 mg/kg/day) to 250 mg/m²/day (10 mg/kg/day) divided in one or two daily infusions, administered from 1 up to 3 consecutive days before allogeneic HPCT; Max cumulative dose: 375 mg/m² (15 mg/kg).
Leukaemia, Thalassemia, Sickle cell anemia:
250 mg/m²/day (10 mg/kg/day) divided in two daily infusions, administered before allogeneic HPCT. In thalassemia, can also use range of 200-250 mg/m²/day.
Genetic diseases:
125 mg/m²/day (5 mg/kg/day) as a single daily infusion, for 2 consecutive days before allogeneic HPCT; Max cumulative dose: 250 mg/m² (10 mg/kg).
Adverse Effect :
Bone marrow suppression, fatigue, weakness, rash, urticaria, laryngeal edema, asthma, anaphylactic shock, wheezing, contact dermatitis, pain at the injection site, nausea, vomiting, abdominal pain, anorexia, dysuria, urinary retention, dizziness, headache, blurred vision, dermatitis, alopecia, skin depigmentation.
Interaction :
Nitrogen Mustard or Cyclophosphamide, Irradiation: Would serve to intensify toxicity rather than to enhance therapeutic response.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | IM: Use a reduced dose with caution |
| 10-20 | IM: Use a reduced dose with caution |
| <10 | IM: Use a reduced dose with caution |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Unknown dialysability. Dose as in GFR<10 mL/min |
| HD | Dialysed. Dose as in GFR<10 mL/ min |
| HDF/High flux | Dialysed. Dose as in GFR<10 mL/ min |
| CAV/VVHD | Dialysed. Dose as in GFR=10– 20 mL/min |
Hepatic Dose :
Moderate to severe hepatic impairment or bilirubin concentrations greater than 1.5 times the upper limit of normal and any aspartate aminotransferase levels: Dose may need to be reduced as the metabolism of the drug will be affected and the levels can build up, leading to toxicity.