Doxorubicin and methotrexate on a weekly schedule in patients with sarcomas

Fifty-five sarcoma patients with advanced measurable disease were treated with a doxorubicin and methotrexate combination in which both drugs were given on a weekly schedule. Patients received doxorubicin and methotrexate at three prospectively evaluated treatment levels with doxorubicin dosage ranging from 0.5 to 0.725 mg/kg/week and methotrexate dosage ranging from 0.25 to 0.375 mg/kg/week. Objective responses were seen in 11 of 39 (28%) patients receiving the two higher doxorubicin-methotrexate treatment levels where doxorubicin dose was greater than 0.5 mg/kg/week compared to only 2 of 16 (12%) patients receiving lower doxorubicin levels (p less than 0.05), suggestive of a dose-response relationship. Toxicity of this regimen was manageable but stomatitis was appreciable, seen in 30% of patients. These results support the activity of weekly doxorubicin in sarcoma therapy. However, no apparent improvement was associated with addition of conventional dose methotrexate to weekly doxorubicin treatment.