title: Actinomycin D for methotrexate-failed low-risk gestational trophoblastic neoplasia.
abstract: OBJECTIVE
  To determine outcomes and factors associated with failure of 5-day actinomycin D for treatment of methotrexate-failed low-risk gestational trophoblastic neoplasia (GTN).
  
  
  METHODS
  We reviewed the records of 358 patients treated with methotrexate 0.4 mg/kg (max 25 mg) IV push q.d. x 5 d every 14 d for FIGO-defined, low-risk GTN between 1979 and 2009. Actinomycin D 0.5 mg IV push q.d. x 5 d every 14 d was given to 64 of 68 patients (18%) who failed methotrexate: 48 (75%) for resistance and 16 (25%) for toxicity. Adjuvant surgery was used in selected patients. Clinical response and survival as well as factors affecting outcomes were analyzed retrospectively.
  
  
  RESULTS
  The complete response rate to secondary chemotherapy with actinomycin D for failed methotrexate treatment of low-risk GTN was 75% (48/64), including 71% (34/48) for methotrexate resistance and 88% (14/16) for methotrexate toxicity. All 20 patients (6%) who failed sequential single-agent chemotherapy with methotrexate and actinomycin D were placed into permanent remission with the use of multiagent chemotherapy with or without surgery. The only factor significantly associated with resistance to secondary actinomycin D chemotherapy was clinicopathologic diagnosis of choriocarcinoma versus postmolar GTN (56% versus 20%, p = 0.025).
  
  
  CONCLUSIONS
  Actinomycin D 0.5 mg IV q.d. x 5 d every 14 d used as secondary therapy in methotrexate-failed low-risk GTN resulted in a 75% complete response rate and eventual 100% cure with subsequent multiagent chemotherapy with or without surgery. Resistance to sequential methotrexate and actinomycin D chemotherapy was significantly associated with original FIGO score > or = 3 and clinicopathologic diagnosis of choriocarcinoma.
authors: John I. Brewer Trophoblastic Disease Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. jlurain@nmff.org
authors: John R
authors: JR
authors: Lurain
authors: Eloise
authors: E
authors: Chapman-Davis
authors: Anna V
authors: AV
authors: Hoekstra
authors: Julian C
authors: JC
authors: Schink
mesh_terms: D000293:Adolescent; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003609:Dactinomycin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D031901:Gestational Trophoblastic Disease / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007044:Hysterectomy; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D011247:Pregnancy; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D055815:Young Adult
chemical_list: D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D003609:Dactinomycin; D008727:Methotrexate