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Pharmacokinetics of high-dose methotrexate with citrovorum factor rescue.

The methotrexate (MTX)-plasma concentrations of 172 high-dose infusions over the range of 50-200 mg/kg were measured over the 72-hour period following the beginning of infusion. Pharmacokinetic analysis shows that a biexponential function adequately describes the plasma decay for all doses. The distribution of plasma clearances over the patient population at a given dose has been characterized by a biexponential clearance function and associated time-dependent variance. It is found that when each of the plasma clearance functions are scaled by their respective dose, the 1 SD bands about the resulting unit dose curves overlap throughout their time ranges and are therefore insignificantly different from one another. Thus, the plasma clearance over the 50-200-mg/kg range may be represented by a single dose-scalable biexponential model with half-lives of 1.8 +/- 0.1 and 8.4 +/- 0.5 hours. For a given maximum allowable plasma-MTX level (eg, 10(-5) M at 24 hours), the variance of the clearance distribution is shown to predict the expected fraction of patients who will require intensified rescue. Urinary clearance has been determined at 104 +/- 8 ml/minute over the dose range of 50-300 mg/kg and only 60% of the MTX was excreted in the urine by 72 hours.

Adolescent↗

[High-dose methotrexate with citrovorum factor rescue (HD-MTX-CFR) in the treatment of malignant solid tumors--clinical analysis of 62 patients].

From 1977 to 1982, 62 patients with various advanced malignant solid tumors were treated by HD-MTX-CFR therapy and totally 129 courses were given. Majority of the patients suffered from malignant lymphoma (10), osteogenic sarcoma (11), lung cancer (16), esophageal cancer (3), breast cancer (3) and malignant melanoma (4). All were confirmed by cytology or pathology except one primary liver cancer. There were clinically measurable lesions in 59 patients for evaluation of the treatment, and 3 osteogenic sarcoma patients without metastasis were given a postoperative adjuvant chemotherapy. 33 out of 62 had received chemotherapy and/or radiotherapy before. Dose of MTX ranged from 2 to 3 gm per course in most patients and dose of CF, from 9 to 12 mg every 6 hours for 3 days. 2 (3.4%) patients achieved complete remission (1 osteogenic sarcoma and 1 malignant lymphoma) and 8 (13.6%), partial remission (1 osteogenic sarcoma, 5 malignant lymphoma, 1 esophageal cancer and 1 breast cancer) with a total response rate of 15.9%. No response was observed in all 16 lung cancers. The main side effects of HD-MTX-CFR therapy were leukopenia, thrombocytopenia, elevation of SGPT, nausea, vomiting, mucositis, skin rash, fever and fatigue. All patients were followed more than 3 years. 4 patients are still alive (9, 9, 4 and 7 years, respectively), including 3 osteogenic sarcoma patients who received postoperative adjuvant chemotherapy and 1 mycosis fungoides.

Adolescent↗