TY - JOUR
T1 - An international randomized phase III trial of pulse actinomycin-D versus multi-day methotrexate for the treatment of low risk gestational trophoblastic neoplasia; NRG/GOG 275
AU - Schink, Julian C.
AU - Filiaci, Virginia
AU - Huang, Helen Q.
AU - Tidy, John
AU - Winter, Matthew
AU - Carter, Jeanne
AU - Anderson, Nancy
AU - Moxley, Katherine
AU - Yabuno, Akira
AU - Taylor, Sarah E.
AU - Kushnir, Christina
AU - Horowitz, Neil
AU - Miller, David S.
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2020/8
Y1 - 2020/8
N2 - Objectives: Methotrexate and actinomycin-D are both effective first-line drugs for low-risk (WHO score 0–6) Gestational Trophoblastic Neoplasia (GTN) with considerable debate about which is more effective, less toxic, and better tolerated. The primary trial objective was to test if treatment with multi-day methotrexate (MTX) was inferior to pulse actinomycin-D (ACT-D). Secondary objectives included evaluation of severity and frequency of adverse events, and impact on quality of life (QOL). Methods: This was a prospective international cooperative group randomized phase III two arm non-inferiority study (Clinical Trials Identifier: (NCT01535053). The control arm was ACT-D; the experimental arm was multi-day MTX regimen (institutional preference of 5 or 8 day). Outcome measures included complete response rate, recurrence rate, toxicity, and QOL as measured by FACT-G and FACIT supplemental items. Results: The complete response rates for multi-day methotrexate and pulse actinomycin-D were 88% (23/26 patients) and 79% (22/28 patients) (p = NS) respectively, there were two recurrences in each arm, and 100% of patients survived. Significant toxicity was minimal, but mouth sores (mucositis), and eye pain were significantly more common in the MTX arm (p = 0.001 and 0.01 respectively). Quality of life showed no significant difference in overall quality of life, body image, sexual function, or treatment related side effects. The study was closed for low accrual rate (target 384, actual accrual 57), precluding statistical analysis of the primary objective. Conclusions: The complete response rate for multi-day methotrexate was higher than actinomycin-D, but did not reach statistical significance. The multi-day MTX regimens were associated with significantly more mucositis and were significantly less convenient.
AB - Objectives: Methotrexate and actinomycin-D are both effective first-line drugs for low-risk (WHO score 0–6) Gestational Trophoblastic Neoplasia (GTN) with considerable debate about which is more effective, less toxic, and better tolerated. The primary trial objective was to test if treatment with multi-day methotrexate (MTX) was inferior to pulse actinomycin-D (ACT-D). Secondary objectives included evaluation of severity and frequency of adverse events, and impact on quality of life (QOL). Methods: This was a prospective international cooperative group randomized phase III two arm non-inferiority study (Clinical Trials Identifier: (NCT01535053). The control arm was ACT-D; the experimental arm was multi-day MTX regimen (institutional preference of 5 or 8 day). Outcome measures included complete response rate, recurrence rate, toxicity, and QOL as measured by FACT-G and FACIT supplemental items. Results: The complete response rates for multi-day methotrexate and pulse actinomycin-D were 88% (23/26 patients) and 79% (22/28 patients) (p = NS) respectively, there were two recurrences in each arm, and 100% of patients survived. Significant toxicity was minimal, but mouth sores (mucositis), and eye pain were significantly more common in the MTX arm (p = 0.001 and 0.01 respectively). Quality of life showed no significant difference in overall quality of life, body image, sexual function, or treatment related side effects. The study was closed for low accrual rate (target 384, actual accrual 57), precluding statistical analysis of the primary objective. Conclusions: The complete response rate for multi-day methotrexate was higher than actinomycin-D, but did not reach statistical significance. The multi-day MTX regimens were associated with significantly more mucositis and were significantly less convenient.
KW - Actinomycin-D
KW - GOG
KW - Gestational trophoblastic neoplasia
KW - Multi-day methotrexate
KW - NRG
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U2 - 10.1016/j.ygyno.2020.05.013
DO - 10.1016/j.ygyno.2020.05.013
M3 - Review article
C2 - 32460997
AN - SCOPUS:85085207213
SN - 0090-8258
VL - 158
SP - 354
EP - 360
JO - Gynecologic oncology
JF - Gynecologic oncology
IS - 2
ER -