title: Risk adapted single-agent dactinomycin or carboplatin for second-line treatment of methotrexate resistant low-risk gestational trophoblastic neoplasia.
abstract: OBJECTIVE
  To evaluate the outcome of patients treated with second-line chemotherapy for methotrexate-resistant low-risk GTN at the Sheffield Centre, UK between 2001 and 2015, including the novel use of single-agent carboplatin as a strategy to reduce exposure to combination chemotherapy.
  
  
  METHODS
  392 low-risk GTN patients were treated with first-line methotrexate. The selection of chemotherapy regimen following methotrexate-resistance depended on the volume of residual disease as indicated by the serum hCG value at the time, with patients switching to either single-agent dactinomycin at an hCG level<150IU/L from 2001-2010 and <300IU/L since 2010, or to combination treatment with etoposide/dactinomycin (EA) above these thresholds. In order to reduce exposure to more toxic combination chemotherapy regimens, our treatment policy was revised in 2011, with the recommendation of single-agent carboplatin as an alternative to EA at hCG levels >300IU/L.
  
  
  RESULTS
  136 (35%) of 392 received second-line chemotherapy following methotrexate-resistance. 59 patients received single-agent dactinomycin with 53 (90%) patients achieving complete hCG response, 3 patients requiring combination chemotherapy or surgery, and 3 patients subsequently spontaneously resolving. 56 patients received EA chemotherapy with hCG complete response in 50 (89%) patients, and the remaining 6 patients were cured with further multi-agent chemotherapy or surgery. With carboplatin, 17/21 (81%) achieved an overall complete hCG response rate, with 4 patients requiring third-line EA. Carboplatin was well tolerated with no significant alopecia; myelosuppression was the most significant toxicity. Overall survival for all patients was 100%.
  
  
  CONCLUSIONS
  These data show the continued excellent outcomes for methotrexate-resistant low-risk patients treated with single-agent dactinomycin or EA. Our experience with carboplatin is promising and provides an alternative regimen for methotrexate-resistant low-risk disease that avoids alopecia and in-patient treatment.
authors.affiliation: Sheffield Centre for Trophoblastic Disease, Weston Park Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, S10 2SJ, United Kingdom. Electronic address: matthew.winter@sth.nhs.uk.
authors.forename: M C
authors.initials: MC
authors.lastname: Winter
authors.affiliation: Sheffield Centre for Trophoblastic Disease, Weston Park Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, S10 2SJ, United Kingdom.
authors.forename: J A
authors.initials: JA
authors.lastname: Tidy
authors.affiliation: Sheffield Centre for Trophoblastic Disease, Weston Park Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, S10 2SJ, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Hills
authors.affiliation: Sheffield Centre for Trophoblastic Disease, Weston Park Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, S10 2SJ, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Ireson
authors.affiliation: Sheffield Centre for Trophoblastic Disease, Weston Park Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, S10 2SJ, United Kingdom.
authors.forename: S
authors.initials: S
authors.lastname: Gillett
authors.affiliation: Sheffield Centre for Trophoblastic Disease, Weston Park Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, S10 2SJ, United Kingdom.
authors.forename: K
authors.initials: K
authors.lastname: Singh
authors.affiliation: Sheffield Centre for Trophoblastic Disease, Weston Park Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, S10 2SJ, United Kingdom.
authors.forename: B W
authors.initials: BW
authors.lastname: Hancock
authors.affiliation: Sheffield Centre for Trophoblastic Disease, Weston Park Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, S10 2SJ, United Kingdom.
authors.forename: R E
authors.initials: RE
authors.lastname: Coleman
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use*; D006063:Chorionic Gonadotropin / Q000097:blood; D003609:Dactinomycin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D031901:Gestational Trophoblastic Disease / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008727:Methotrexate; D018365:Neoplasm, Residual; D011247:Pregnancy; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D014594:Uterine Neoplasms / Q000097:blood / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D006063:Chorionic Gonadotropin; D003609:Dactinomycin; D016190:Carboplatin; D008727:Methotrexate
keywords: Carboplatin; Gestational trophoblastic neoplasia; Low-risk; Methotrexate-resistance; Second-line chemotherapy