title: Combination chemotherapy for primary treatment of high-risk gestational trophoblastic tumour.
abstract: BACKGROUND
  This is an update of the original review that was published in The Cochrane Database of Systematic Reviews, 2009, Issue 2. Gestational trophoblastic neoplasia (GTN) are malignant disorders of the placenta that include invasive hydatidiform mole, choriocarcinoma, placental-site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT). Choriocarcinoma and invasive hydatidiform mole respond well to chemotherapy: low-risk tumours are treated with single-agent chemotherapy (e.g. methotrexate or actinomycin D), whereas high-risk tumours are treated with combination chemotherapy (e.g. EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine)). Various drug combinations may be used for high-risk tumours; however, the comparative efficacy and safety of these regimens is not clear.
  
  
  OBJECTIVE
  To determine the efficacy and safety of combination chemotherapy in treating high-risk GTN.
  
  
  METHODS
  For the original review, we searched the Cochrane Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL; Issue 2, 2008), MEDLINE, EMBASE and CBM in May 2008. For the updated review, we searched Cochrane Group Specialised Register, CENTRAL, MEDLINE and EMBASE to September 2012. In addition, we searched online clinical trial registries for ongoing trials.
  
  
  METHODS
  Randomised controlled trials (RCTs) and quasi-RCTs comparing first-line combination chemotherapy interventions in women with high-risk GTN.
  
  
  METHODS
  Two review authors independently collected data using a data extraction form. Meta-analysis could not be performed as we included only one study.
  
  
  RESULTS
  We included one RCT of 42 women with high-risk GTN who were randomised to MAC (methotrexate, actinomycin D and chlorambucil) or the modified CHAMOCA regimen (cyclophosphamide, hydroxyurea, actinomycin D, methotrexate, doxorubicin, melphalan and vincristine). There were no statistically significant differences in efficacy of the two regimens; however women in the MAC group experienced statistically significantly less toxicity overall and less haematological toxicity than women in the CHAMOCA group. During the study period, six women in the CHAMOCA group died compared with one in the MAC group. This study was stopped early due to unacceptable levels of toxicity in the CHAMOCA group. We identified no RCTs comparing EMA/CO with MAC or other chemotherapy regimens.
  
  
  CONCLUSIONS
  CHAMOCA is not recommended for GTN treatment as it is more toxic and not more effective than MAC. EMA/CO is currently the most widely used first-line combination chemotherapy for high-risk GTN, although this regimen has not been rigorously compared to other combinations such as MAC or FAV in RCTs. Other regimens may be associated with less acute toxicity than EMA/CO; however, proper evaluation of these combinations in high-quality RCTs that include long-term surveillance for secondary cancers is required. We acknowledge that, given the low incidence of GTN, RCTs in this field are difficult to conduct, hence multicentre collaboration is necessary.
authors: National Key Laboratory of Biotherapy and Cancer Centre,West ChinaHospital, Sichuan University, Chengdu, China.
authors: Linyu
authors: L
authors: Deng
authors: Jing
authors: J
authors: Zhang
authors: Taixiang
authors: T
authors: Wu
authors: Theresa A
authors: TA
authors: Lawrie
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003609:Dactinomycin / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D057239:Early Termination of Clinical Trials; D005260:Female; D031901:Gestational Trophoblastic Disease / Q000188:drug therapy*; D006801:Humans; D006828:Hydatidiform Mole / Q000188:drug therapy; D006918:Hydroxyurea / Q000008:administration & dosage / Q000009:adverse effects; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008558:Melphalan / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D011247:Pregnancy; D018245:Trophoblastic Tumor, Placental Site / Q000188:drug therapy; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D003609:Dactinomycin; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D008558:Melphalan; D002955:Leucovorin; D006918:Hydroxyurea; D008727:Methotrexate