Thigpen 1999.

Methods	RCT
Participants	Multicentre trial from USA A group of 299 patients with advanced or recurrent endometrial adenocarcinoma and not amenable to control with surgery and/or radiotherapy were randomly allocated to therapy of low‐dose (200 mg/d) MPA or high‐dose (1000 mg/d) MPA 145 women with advanced or recurrent endometrial cancer were randomised to low‐dose medroxyprogesterone acetate (MPA) and 154 patients to high‐dose MPA 10 patients (3.3%) were less than 50 years of age, 52 patients (17.4%) were 50 to 59 years of age, 118 (39.5%) were 60 to 69 years of age, 97 (32.4%) were 70 to 79 years of age and 22 (7.4%) were 80 or more years of age 17 (5.7%) women had FIGO stage III, 68 (22.7%) stage IV and 214 (71.6%) had recurrent disease 59 (19.7%) women had Grade 1 disease, 113 (37.8%) had Grade 2 and 127 (42.5%) had Grade 3 disease Histology was adenocarcinoma in 107 (35.8%) women, endometrioid in 81 (27.1%), adenosquamous carcinoma in 38 (12.7%), papillary serous adenocarcinoma in 32 (10.7%), adenoacanthoma in 8 (2.7%), clear‐cell carcinoma in 13 (4.3%) and the remaining 18 (6%) women had other histology 94 (31.5%) women had performance status 0, 137 (45.8%) had status 1 and 68 (22.7%) had status 2
Interventions	145 patients received MPA at dose 200 mg/d 154 patients received MPA at dose 1000 mg/d
Outcomes	Overall survival Response (complete/partial/no response) Progression‐free survival Serum levels of MPA
Notes	There were no appreciable differences between the patients on the 2 regimens with regard to age, performance status, prior treatment with surgery and/or radiotherapy, stage, cell type, or histological grade. In addition, for the 132 patients who had data available for both oestrogen and progesterone receptors there were no appreciable differences observed between the 2 regimens with regard to receptor status. 132 out of 145 women in the low‐dose group died within 4 years, compared to 148 out of 154 in the high‐dose group 134 out of 145 women in the low‐dose group had disease progression within 4 years, compared to 150 out of 154 in the high‐dose group From the Kaplan Meier plot the duration of follow‐up ranged from 0 to 48 months Adjusted hazard ratios using Cox regression for overall and progression‐free survival were reported. The Cox model was adjusted for the initial performance status, progesterone‐receptor level, tumour grade and age. Thrombophlebitis was reported by treatment arm and it was similar in both groups: 5% of women in low‐dose arm versus 4% in high‐dose arm. 2% of women had Grade 3 or 4 thrombophlebitis in both the low‐dose and high‐dose group
Risk of bias
Bias	Authors' judgement	Support for judgement
Adequate sequence generation?	Low risk	"Treatment assignments were permutated randomly within blocks defined by the institutions and receptor status".
Allocation concealment?	Unclear risk	Not reported
Blinding? All outcomes	Unclear risk	Not reported
Incomplete outcome data addressed? All outcomes	Low risk	% analysed for adverse events: 299/299 (100%) For survival outcomes all patients were analysed using appropriate statistical techniques The denominators for the number of women with thrombophlebitis or other adverse events included the 3 women who were not analysed. This was due to details of these 3 women not being provided, but clearly this was unimportant to the results.
Free of selective reporting?	Unclear risk	Insufficient information to assess whether an additional risk of bias exists
Free of other bias?	Unclear risk	Insufficient information to assess whether an additional risk of bias exists
Accurate classifications of outcomes?	Low risk	"Response was defined according to standard GOG criteria".