Is lack of response to single-agent chemotherapy in gestational trophoblastic disease associated with dose scheduling or chemotherapy resistance?
OBJECTIVE
The aim of this study was to determine whether in the management of low-risk gestational trophoblastic neoplasia (GTN) the administration of 5-day courses of 12 microg/kg actinomycin D is effective following the failure of 1.25 mg/m(2) "pulsed" actinomycin D.


METHODS
Patients with low-risk GTN who failed to respond to 1.25 mg/m(2) pulsed actinomycin were switched to the 5-day course of 12 microg/kg actinomycin.


RESULTS
Patients with low-risk GTN who failed to respond to pulsed actinomycin were changed to the same chemotherapy agent, actinomycin D, given as a 5-day course at 12 microg/kg. Four of the five responded and one required methotrexate to achieve remission.


CONCLUSIONS
Pulsed biweekly actinomycin and pulsed weekly methotrexate have been shown to have a higher failure rate than the 5-day regimens of the same medications. This study demonstrates that failure of pulsed actinomycin may be successfully treated by a 5-day course of the same medication. It appears that with the pulsed regimens cytotoxic exposure of trophoblastic cells to the medication is too brief and the 5-day course permits more cells to be in cycle. It is suggested that, following failure of a pulsed regimen, the patient is given the same chemotherapy as a 5-day course, rather than switching from actinomycin to methotrexate or vice versa. This conserves options for chemotherapy in GTN.
Kohorn
Ernest I
EI
Yale Trophoblast Center, Yale University School of Medicine, New Haven, Connecticut 06510, USA. ernest.kohorn@yale.edu
D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D003609:Dactinomycin / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D011247:Pregnancy; D014328:Trophoblastic Neoplasms / Q000188:drug therapy* / Q000601:surgery; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000601:surgery
D000903:Antibiotics, Antineoplastic; D003609:Dactinomycin