Three RCTs (n=524) and 24 non-comparative prospective phase II studies (n=768) were included in the review.
RCTs (3 studies).
One non-blinded RCT (n=194) compared ifosfamide plus mesna uro-protection versus ifosfamide plus mesna plus cisplatin as first-line treatment of chemotherapy-naive women with MMT. It found that the objective RR was significantly greater with ifosfamide plus cisplatin than with ifosfamide alone (54% versus 36%, P=0.03). Combination treatment also significantly increased progression-free survival (median 6.0 versus 4.0 months, P=0.02), but there was no significant difference between treatments for overall survival (median 7.6 versus 9.4 months, P=0.07). Combination treatment was associated with more deaths (6 versus none), increased granulocytopenia (60% versus 36%), anaemia (17% versus 8%), peripheral neurological symptoms (12% versus 1%) and cardiac symptoms (3% versus 0%). Central neurological symptoms were more common with the single-agent regimen (19% versus 14%). The treatment groups were not comparable at baseline and the number of full treatments also differed.
One non-blinded RCT (n=104) compared doxorubicin plus cyclophosphamide versus doxorubicin alone as first-line treatment in chemotherapy-naive women with all histological subtypes of uterine sarcoma. It found the same RR with both treatments in patients with measurable disease (19%). There was no significant difference between treatments for progression-free survival (median 5.1 versus 4.9 months, P=0.22) or overall survival (median 11.6 versus 10.9 months, P=0.55). Combination treatment significantly increased grade 3 and 4 leukocyte toxicity (35% versus 10%).
The third non-blinded RCT (n=226) compared doxorubicin plus DTIC (dimethyl triazenoimidazole carboxamide) versus doxorubicin alone as first or second-line treatment in chemotherapy-naive women with all histological subtypes of uterine sarcoma (mainly LMS and MMT). It found a significantly higher RR with the combination treatment (P<0.05), with higher RRs seen for both MMT (23% versus 10%) and LMS (30% versus 25%). There was no significant difference between treatments for progression-free survival (3.5 versus 5.5 months) or overall survival (7.7 versus 7.3 months). Combination treatment significantly increased grade 3 and 4 haematological (48% versus 20%) and gastrointestinal toxicity (9% versus 2%) compared with the single-agent treatment.
Non-comparative phase II studies (24 studies).
For first-line treatment of patients with LMS, the pooled RR was higher with combination treatment than with single-agent regimens (22.7% versus 7.1%). For patients with MMT, the pooled RR was higher with single agents (22.1% versus 15.7%).
For second-line treatment of patients with LMS, the pooled RR was higher with combination treatment than with single-agent regimens (53.0% versus 7.0%). For patients with MMT, the pooled RR for single-agent regimens was 6.7% (there were no studies of combination chemotherapy in MMT).
The fewest adverse effects were found for first-line treatment with aminothiadiazole, cisplatinum, etoposide and paclitaxel. More adverse effects were found with second-line treatments compared with first-line treatments.