rly stages is usually 5 to 50 mg once weekly. Dose reduction or cessation is guided by patient response and hematologic monitoring. Methotrexate has also been administered twice weekly in doses ranging from 15 to 37.5 mg in patients who have responded poorly to weekly therapy. Combination chemotherapy regimens that include intravenous methotrexate administered at higher doses with leucovorin rescue have been utilized in advanced stages of the disease.
Osteosarcoma- An effective adjuvant chemotherapy regimen requires the administration of several cytotoxic chemotherapeutic agents. In addition to high-dose methotrexate with leucovorin rescue, these agents may include doxorubicin, cisplatin, and the combination of bleomycin, cyclophosphamide and dactinomycin (BCD) in the doses and schedule shown in the table below. The starting dose for high dose methotrexate treatment is 12 grams/m2. If this dose is not sufficient to produce a peak serum methotrexate concentration of 1,000 micromolar (10-3 mol/L) at the end of the methotrexate infusion, the dose may be escalated to 15 grams/m2 in subsequent treatments. If the patient is vomiting or is unable to tolerate oral medication, leucovorin is given IV or IM at the same dose and schedule.
Link MP, Goorin AM, Miser AW, et al; The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. N Engl J of Med 1986; 314(No.25): 1600-1606.
See each respective package insert for full prescribing information. Dosage modifications may be necessary because of drug-induced toxicity.
Drug* Dose* Treatment Weak After Surgery
Methotrexate 12 g/m2 IV as 4 hour infusion (starting dose) 4,5,6,7,11,12,15,16,29,30,44,45
Leucovorin 15 mg orally every six hours for 10 doses starting at 24 hours after start of methotrexate infusion.
Doxorubicin† as a single drug 30 mg/m2/day IV x 3 days 8,17
Doxorubicin† 50 mg/m2 IV 20,23,33,36
Cisplatin† 100 mg/m2 IV 20,23,33,36
Bleomycin† 15 units/m2 IV x 2 days 2,13,26,39,42
Cyclophosphamide† 600 mg/m2 IV x 2 days 2,13,26,39,42
Dactinomycin† 0.6 mg/m2 IV x 2 days 2,13,26,39,42
When these higher doses of methotrexate are to be administered, the following safety guidelines should be closely observed.
GUIDELINES FOR METHOTREXATE THERAPY WITH LEUCOVORIN RESCUE
Administration of methotrexate should be delayed until recovery if:
the WBC count is less than 1500/microliter
the neutrophil count is less than 200/microliter
the platelet count is less than 75,000/microliter
the serum bilirubin level is greater than 1.2 mg/dL
the SGPT level is greater than 450 U
mucositis is present, until there is evidence of healing
persistent pleural effusion is present; this should be drained dry prior to infusion.
Adequate renal function must be documented.
Serum creatinine must be normal, and creatinine clearance must be greater than 60 mL/min, before initiation of therapy.
Serum creatinine must be measured prior to each subsequent course of therapy. If serum creatinine has increased by 50% or more compared to a prior value, the creatinine clearance must be measured and documented to be greater than 60 mL/min (even if the serum creatinine is still within the normal range).
Patients must be well hydrated, and must be treated with sodium bicarbonate for urinary alkalinization.
Administer 1,000 mL/m2 of in |
