Development of single-agent chemotherapy regimens for gestational trophoblastic disease.
Single-agent chemotherapy for nonmetastatic gestational trophoblastic disease is most successful for patients who have had an antecedent molar pregnancy with a plateau or persistent beta-human chorionic gonadotropin elevation after molar evacuation. Traditionally, single-agent, five-day, intramuscular methotrexate has been associated with high cure rates, as has methotrexate with citrovorum factor rescue, which reduces toxicity. Standard definitions of low-risk gestational trophoblastic disease and response assessment are critical to a comparison of prognostic features related to single-agent therapy success. Methotrexate with folinic acid rescue administered as primary therapy does achieve an excellent therapeutic outcome with limited chemotherapy exposure but at increased cost. The weekly intramuscular methotrexate Gynecologic Oncology Group (GOG) regimen is inexpensive and allows close monitoring of disease status. Single-dose or pulsed actinomycin-D provides a high level of complete response, although gastrointestinal toxicity, mainly nausea and vomiting, is quite common. Management of first-line chemotherapy failures is unclear, although in the GOG methotrexate trial it was evident that another agent, such as actinomycin-D, should be used to provide the highest success rate. The use of a single agent in low-risk metastatic trophoblastic disease (lung and/or vaginal metastases) depends upon restricting it to patients who have not failed prior chemotherapy, have a low World Health Organization score and have no evidence of the presence of choriocarcinoma, but a much higher first-line failure rate should be anticipated than in nonmetastatic disease. Other single-agent regimens have been proposed that are worthy of investigation to create a safer, more efficacious and more convenient regimen for low-risk gestational trophoblastic disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Homesley
H D
HD
Section on Gynecologic Oncology, Comprehensive Cancer Center of Wake Forest University, Winston-Salem, North Carolina 27157-1065.
D006063:Chorionic Gonadotropin / Q000097:blood; D018997:Chorionic Gonadotropin, beta Subunit, Human; D002985:Clinical Protocols; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D003609:Dactinomycin / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D016527:Drug Costs; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D002955:Leucovorin / Q000627:therapeutic use*; D008727:Methotrexate / Q000627:therapeutic use*; D009367:Neoplasm Staging; D010446:Peptide Fragments / Q000097:blood; D011247:Pregnancy; D011379:Prognosis; D012307:Risk Factors; D017211:Treatment Failure; D014328:Trophoblastic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D014594:Uterine Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D014620:Vacuum Extraction, Obstetrical
D006063:Chorionic Gonadotropin; D018997:Chorionic Gonadotropin, beta Subunit, Human; D010446:Peptide Fragments; D003609:Dactinomycin; D002955:Leucovorin; D008727:Methotrexate