Salvage combination chemotherapy with 5-fluorouracil and actinomycin D for patients with refractory, high-risk gestational trophoblastic tumors.
BACKGROUND
The objective of this study was to evaluate the efficacy and toxicity of a high-dose 5-fluorouracil and actinomycin D regimen (the FA regimen) as salvage chemotherapy for patients with high-risk gestational trophoblastic tumors (GTTs).


METHODS
From 1985 to 1997, 10 patients with refractory, high-risk GTTs were treated with the FA regimen at Chiba University Hospital. Of those 10 patients, 7 patients developed drug resistance to methotrexate, etoposide, and actinomycin D combination chemotherapy (the MEA regimen); 1 patient developed recurrent disease after receiving the MEA regimen; and 2 patients developed recurrent disease after receiving combination chemotherapy with etoposide, methotrexate, and actinomycin D alternating with cyclophosphamide and vincristine (the EMA/CO regimen). The hematologic toxicity of the FA regimen was graded at every chemotherapy course.


RESULTS
With the FA regimen, the survival rate was 80.0% (8 of 10 patients) for a mean follow-up of 10 years. Two patients died due to multidrug resistance, and two patients subsequently developed recurrent disease. The two patients with recurrent disease were successfully salvaged again with the MEA regimen. The toxicity of the FA regimen was evaluated in 78 cycles. Myelosuppression seemed to be the dose-limiting toxicity, and the incidences of World Health Organization Grade 4 leukocytopenia and thrombocytopenia were 6.4% and 3.8%, respectively, of 78 cycles.


CONCLUSIONS
Although etoposide-containing chemotherapy is currently the most effective and well-tolerated regimen for patients with high-risk GTTs, 20-30% of patients develop resistance to etoposide-containing regimens. Salvage combination chemotherapy with FA is effective for these patients with refractory disease, and the toxicity is predictable and manageable.
Matsui
Hideo
H
Department of Obstetrics and Gynecology, Chiba University School of Medicine, Chiba, Japan. hmatsui@med.m.chiba.u.ac.jp
Suzuka
Kiyomi
K
Iitsuka
Yoshinori
Y
Yamazawa
Koji
K
Tanaka
Naotake
N
Mitsuhashi
Akira
A
Seki
Katsuyoshi
K
Sekiya
Souei
S
D000328:Adult; D003609:Dactinomycin / Q000008:administration & dosage; D018432:Drug Resistance, Multiple; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011247:Pregnancy; D012189:Retrospective Studies; D012307:Risk Factors; D016879:Salvage Therapy; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced; D014328:Trophoblastic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000473:pathology
D003609:Dactinomycin; D005472:Fluorouracil