HIGH-DOSE METHOTREXATE FOR GESTATIONAL TROPHOBLASTIC DISEASE

Eighty patients with low-risk and 5 patients with intermediate-risk ge stational trophoblastic neoplasia (GTN) (WHO classification) were trea ted with single-agent high-dose methotrexate with folinic acid rescue (MTX/FAR). By the NCI classification, 65 patients had nonmetastatic GT N, 13 patients had low-risk metastatic GTN, and 7 patients had high-ri sk metastatic GTN. Seventy-one (84%) patients achieved remission (beta HCG less than or equal to 5 IU/liter) with MTX/FAR, whereas 14 (16%) failed to achieve remission with MTX/FAR alone. All failures were salv aged with second-line therapies. Patients successfully treated with MT X/FAR required a median of 4 courses to achieve remission, and a media n of 2 consolidative courses. Factors found predictive of failure with MTX/FAR were pretreatment beta HCG (P = 0.003), prior history of GTN (P < 0.04), and time from termination of antecedent pregnancy to initi ation of treatment (P < 0.05). No significant difference was noted bet ween the ''success'' and ''failure'' groups with respect to MTX dose o r infusion time, the timing and dosage of folinic acid rescue, the num ber of courses of MTX, or the mean interval between courses. Multivari ate analysis revealed that the pretreatment beta HCG (P < 0.01) and sh ort time from termination of antecedent pregnancy to initiation of tre atment (P < 0.03) were independently significant for failure. No signi ficant (grade 3/4) hematologic or gastrointestinal toxicity occurred, and no treatment delays or dose reductions were required. This regimen is both effective and well tolerated; however, the theoretical advant ages of high-dose methotrexate do not appear to offer any clinical adv antage over conventional dose MTX in low- and intermediate-risk GTN. ( C) 1994 Academic Press, Inc.