Phase II trial of vaginal cuff brachytherapy followed by chemotherapy in early stage endometrial cancer patients with high-intermediate risk factors.

Objective: To determine the progression free survival (PFS), toxicity, and patterns of failure for early stage, high-intermediate risk (H-IR) patients in a phase II trial with adjuvant vaginal cuff brachytherapy (VCB) and three cycles of carboplatin and paclitaxel.

Methods: Surgically staged patients with stage I-IIb endometrial cancer with H-IR factors were treated with VCB (2100cGy) followed by three cycles of carboplatin (AUC 6) and paclitaxel (175 mg/m(2)). The primary endpoint was PFS at 2 years, with toxicity and sites of failure as secondary endpoints. Toxicity was assessed by patient report (CTCAE v. 3) as well as by delays or dose modifications in treatment.

Results: All patients completed VCB and 19/23 (83%) completed both VCB and 3 cycles of chemotherapy. Mean time to complete VCB was 14.5 days with minimal acute toxicity noted. At 6 months, all toxicity related to VCB had resolved. In total 60 cycles of chemotherapy were given, with one dose reduction (1.6%) for grade 2 neuropathy and seven delays (11.6%) in treatment due to hematologic toxicity. At a median follow-up of 44.5 months, 91% of patients remained progression free at 2 years. Four patients experienced a recurrence; they recurred both locally and distant.

Conclusions: Adjuvant therapy with VCB and chemotherapy is well tolerated in a population of patients with H-IR endometrial carcinoma and provides 2 year PFS of 91%. A randomized trial is currently underway to assess whether combined VCB and chemotherapy reduces the rate of recurrence compared to external beam radiation therapy (EBRT) in this patient population.