Limpongsanurak 2001.

Methods	RCT conducted in Thailand. Participants were recruited between 1989 and 1994.
Participants	Women diagnosed with high‐risk CM (with histological diagnosis) within 1 week of evacuation of molar tissue. Women were considered 'high risk' if they had at least 1 of the following characteristics: initial serum hCG > 100,000 mIU/mL; uterine size larger than dates; theca lutein cysts > 6 cm; age > 40 years; or associated medical and epidemiological factors including previous GTD, toxaemia, hyperthyroidism, trophoblast embolisation or disseminated intravascular coagulation. 60 participants were randomised into 2 groups (30:30).
Interventions	Arm 1: IV actinomycin D (10 µg/kg) for 5 days, within 1 week of evacuation of molar tissue. Arm 2: IV fluids and analgesic drugs for 5 days within 1 week of evacuation of molar tissue.
Outcomes	Efficacy: incidence of GTN. Adverse effects: incidence of gastrointestinal toxicity, myelotoxicity, hair loss, mouth ulcers. Time to diagnosis of GTN.
Notes	The gestational age at diagnosis of HM was 13.8 ± 3.0 weeks in the intervention group and 13.6 ± 4.2 weeks in the control group. Women were followed up for 1 year with hCG assays every 2 weeks for 3 months, then monthly for 3 months, then every 2 months up to 1 year. The diagnosis of GTN was made in all women in the P‐Chem group (4/4) and 12/15 women in the control group according to the following criteria: rising hCG levels for 2 weeks or a plateau for 3 weeks; persistent or recurrent vaginal bleeding with detectable hCG levels; clinical or histological evidence of invasive mole, choriocarcinoma or metastases with persistently high or rising hCG values. Histology was obtained for 3 participants. 2 out of 4 women in the P‐Chem group and 3 out of 15 in the control group were lost to follow‐up after diagnosis of GTN; therefore 5 women with GTN received no subsequent treatment and data were insufficient to compare the number of chemotherapy courses received in each group. Side effects were reported as percentages and only recorded for the P‐Chem group, as follows: stomatitis (10%), nausea/vomiting (10%), oral ulcers (3.3%) and hair loss (13.3%). All adverse effects were grade 1 except for 2 patients with patchy alopecia (grade 2).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random sequence was generated by lot‐drawing (information obtained by e‐mail correspondence with Dr Limpongsanurak).
Allocation concealment (selection bias)	Low risk	Sealed opaque envelopes (information obtained by e‐mail correspondence with Dr Limpongsanurak).
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Described as double‐blind.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Described as double‐blind, but the details of outcome assessment are unclear.
Incomplete outcome data (attrition bias) All outcomes	Low risk	1 woman in the P‐Chem group was lost to follow‐up 1 month after treatment and not included in the primary outcome analysis.
Selective reporting (reporting bias)	Low risk	All pre‐specified outcomes were reported.
Other bias	Low risk	Baseline characteristics and risk factors for disease progression were similar between the groups.

CM: complete mole; ERPC: evacuation of retained products of conception; GTD: gestational trophoblastic disease; GTN: gestational trophoblastic neoplasia; hCG: β‐human chorionic gonadotrophin; IM: intramuscular; IV: intravenous; P‐Chem: prophylactic chemotherapy; RCT: randomised controlled trial; SD: standard deviation.