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.