title: High-dose methotrexate for gestational trophoblastic disease.
abstract: Eighty patients with low-risk and 5 patients with intermediate-risk gestational trophoblastic neoplasia (GTN) (WHO classification) were treated with single-agent high-dose methotrexate with folinic acid rescue (MTX/FAR). By the NCI classification, 65 patients had nonmetastatic GTN, 13 patients had low-risk metastatic GTN, and 7 patients had high-risk metastatic GTN. Seventy-one (84%) patients achieved remission (beta HCG < or = 5 IU/liter) with MTX/FAR, whereas 14 (16%) failed to achieve remission with MTX/FAR alone. All failures were salvaged with second-line therapies. Patients successfully treated with MTX/FAR required a median of 4 courses to achieve remission, and a median 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 initiation of treatment (P < 0.05). No significant difference was noted between the "success" and "failure" groups with respect to MTX dose or infusion time, the timing and dosage of folinic acid rescue, the number of courses of MTX, or the mean interval between courses. Multivariate analysis revealed that the pretreatment beta HCG (P < 0.01) and short time from termination of antecedent pregnancy to initiation of treatment (P < 0.03) were independently significant for failure. No significant (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 advantages of high-dose methotrexate do not appear to offer any clinical advantage over conventional dose MTX in low- and intermediate-risk GTN.
authors.affiliation: Department of Obstetrics and Gynecology, University of Toronto, Sunnybrook Health Science Centre, Ontario, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Elit
authors.forename: A
authors.initials: A
authors.lastname: Covens
authors.forename: R
authors.initials: R
authors.lastname: Osborne
authors.forename: A
authors.initials: A
authors.lastname: Gerulath
authors.forename: J
authors.initials: J
authors.lastname: Murphy
authors.forename: B
authors.initials: B
authors.lastname: Rosen
authors.forename: J
authors.initials: J
authors.lastname: Sturgeon
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D006063:Chorionic Gonadotropin / Q000097:blood; D018997:Chorionic Gonadotropin, beta Subunit, Human; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000097:blood; D011247:Pregnancy; D012074:Remission Induction; D016896:Treatment Outcome; D014328:Trophoblastic Neoplasms / Q000097:blood / Q000188:drug therapy*; D014594:Uterine Neoplasms / Q000097:blood / Q000188:drug therapy*
chemical_list: D014408:Biomarkers, Tumor; D006063:Chorionic Gonadotropin; D018997:Chorionic Gonadotropin, beta Subunit, Human; D010446:Peptide Fragments; D002955:Leucovorin; D008727:Methotrexate