Phase II trial of adjuvant pelvic radiation "sandwiched" between ifosfamide or ifosfamide plus cisplatin in women with uterine carcinosarcoma

Abstract

Objective: Uterine carcinosarcoma (CS) is a rare uterine tumor with an extremely poor prognosis. In the adjuvant setting, efficacy has been shown with radiotherapy (RT), systemic chemotherapy, or both. This is the first report describing the efficacy and toxicity of adjuvant ifosfamide or ifosfamide plus cisplatin "sandwiched" with RT in patients with surgically staged and completely resected uterine carcinosarcoma.

Methods: Women with surgically staged CS with no gross residual disease were initially administered ifosfamide (1.2 g/m(2)/day×5 days) with cisplatin (20 mg/m(2)/day×5 days) every 3 weeks for 3 cycles followed by pelvic external beam RT and brachytherapy followed by 3 additional cycles of ifosfamide (1.0 g/m2/day) with cisplatin (20 mg/m(2)/day×5 days) every 3 weeks. Similar to the GOG trial in recurrent CS (Sutton et al., 2000), the addition of cisplatin added toxicity without additional efficacy, so mid-study, the cisplatin was eliminated from the regimen. Toxicities were recorded and disease-free survival (DFS) was calculated with Kaplan-Meier statistical methods.

Results: In total, 12 patients received ifosfamide and cisplatin and 15 patients received ifosfamide alone, both 'sandwiched' with RT. The median follow up was 35.9 months (range 6-88). The 2 year DFS was similar in both the ifosfamide/cisplatin and ifosfamide groups (log-rank p=0.16), so they were combined for analysis. 19 patients (70%) completed the protocol. As expected, stage 1 patients had a better 2-year DFS (18.75 ± 1.12 months; log-rank p=0.008 when compared to stages 2, 3, 4). Also, in stages 2, 3 and 4 patients, the DFS was 15.81 ± 1.73 months. Grade 3/4 neutropenia, anemia and thrombocytopenia occurred in 18%, 4% and 4% of cycles, respectively.

Conclusions: Ifosfamide "sandwiched" with RT appears to be an efficacious regimen for surgically staged CS patients with no residual disease, even in patients with advanced stage. The addition of cisplatin to the regimen added toxicity without improving efficacy. Even with ifosfamide alone, the efficacy of this 'sandwich' regimen comes with a moderate but tolerable toxicity profile.

Trial registration: ClinicalTrials.gov NCT00231842.

Fig. 1

Treatment numbers on protocol. Toxicity analysis performed on the 27 patients who received at least one dose of chemotherapy. Survival analysis was performed in all patients who received the first 3 cycles of chemotherapy followed by RT.

Fig. 2

Kaplan-Meier survival curve of early stage (stage I and II) and late stage (stage III and IV) uterine CS patients treated with radiation “sandwiched” between three cycles of cisplatin/ifosfamide or ifosfamide chemotherapy before and after RT. 2-year DFS for early stage patients was 18.07 ± 1.21 (mean ± standard error) months and for advanced stage patients was 15.72 ± 1.79 months.