title: Treatment of nonmetastatic and metastatic low-risk gestational trophoblastic neoplasia: factors associated with resistance to single-agent methotrexate chemotherapy.
abstract: OBJECTIVE
  To determine factors associated with resistance to methotrexate treatment of low-risk gestational trophoblastic neoplasia (GTN).
  
  
  METHODS
  We reviewed the records of 358 patients with low-risk GTN (FIGO stage I and stages II-III, score<7) treated initially with methotrexate 0.4 mg/kg (max 25mg) IV push daily × 5 days every 14 days between 1979 and 2009. Actinomycin D 0.5mg IV push daily × 5 days every 14 days was used in 64 patients who developed resistance or toxicity to initial methotrexate chemotherapy, and combination drug regimens were used in 20 patients who failed single-agent chemotherapy. Adjuvant surgery was used in 34 selected patients. Clinical response and survival as well as factors affecting outcomes were analyzed retrospectively.
  
  
  RESULTS
  The complete response rate to initial methotrexate chemotherapy was 81% (290/358) and the complete response rate to actinomycin D as secondary therapy was 75% (48/64), for an overall complete response rate to sequential single-agent chemotherapy of 94% (338/358). The remaining 20 patients (6%) were all placed into permanent remission with the use of multiagent chemotherapy with or without surgery. Resistance to initial methotrexate chemotherapy was associated with increasing FIGO score (p<.0001), clinicopathologic diagnosis of choriocarcinoma (p=.028), higher pretreatment hCG (p=0.001) and presence of metastatic, disease (p=.018).
  
  
  CONCLUSIONS
  Sequential single-agent chemotherapy with methotrexate (0.4 mg/kg-max 25mg) followed by actinomycin D (0.5mg) each given IV push for 5 consecutive days every other week for treatment of low-risk GTN resulted in only 6% of patients requiring multiagent chemotherapy and a 100% survival rate.
authors.affiliation: Department of Obstetrics and Gynecology, John I. Brewer Trophoblastic Disease Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Eloise
authors.initials: E
authors.lastname: Chapman-Davis
authors.forename: Anna V
authors.initials: AV
authors.lastname: Hoekstra
authors.forename: Alfred W
authors.initials: AW
authors.lastname: Rademaker
authors.forename: Julian C
authors.initials: JC
authors.lastname: Schink
authors.forename: John R
authors.initials: JR
authors.lastname: Lurain
mesh_terms: D000293:Adolescent; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D003131:Combined Modality Therapy; D003609:Dactinomycin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D031901:Gestational Trophoblastic Disease / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D009367:Neoplasm Staging; D011247:Pregnancy; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D003609:Dactinomycin; D008727:Methotrexate