A phase I study of docetaxel as a radio-sensitizer for locally advanced squamous cell cervical cancer.

OBJECTIVES: This study was designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly docetaxel with concurrent radiotherapy (RT) for the primary treatment of locally advanced squamous cell carcinoma of the cervix. METHODS: Eligible patients included those with locally advanced squamous cell cervical cancer without para-aortic lymph node involvement. Docetaxel dose levels were 20 mg/m(2), 30 mg/m(2) and 40 mg/m(2) given intravenously weekly for 6 cycles. Three patients were to be treated at each dose level and 6 to receive the MTD. RESULTS: Fifteen patients completed 4-6 cycles of chemotherapy. One of three patients experienced 2 delayed grade 3 severe adverse events (SAE) at the 20 mg/m(2) dose level consisting of colonic and ureteral obstruction. At the 30 mg/m(2) dose level, 1/4 patients had a probable treatment-related celiotomy due to obstipation and a necrotic tumor. Of the 8 patients treated at the 40 mg/m(2) dose level, 1 experienced grade 3 pneumonitis, likely treatment related. Overall, 10/15 (67%) experienced grade 1 or 2 diarrhea, 6 had grade 2 hematologic toxicity, and 2 had grade 2 hypersensitivity. 10 of 16 patients (67%) had no evidence of disease with follow-up ranging from 10-33 months (average 23 months). CONCLUSIONS: The recommended phase II dose of docetaxel administered weekly with concurrent radiotherapy for locally advanced squamous cell carcinoma of the cervix is 40 mg/m(2).

Concordance of gross surgical and final fixed margins in vulvar intraepithelial neoplasia 3 and vulvar cancer.

OBJECTIVE: To prospectively evaluate the concordance of initial surgical vulvar margins and final fixed margins and to determine the amount of microscopic pathology of grossly negative margins in women with vulvar intraepithelial neoplasia (VIN) 3 or vulvar carcinoma. STUDY DESIGN: Women with VIN 3 or vulvar carcinoma undergoing surgical excision were identified. Prior to excision, acetic acid was used to highlight the lesions, and 2 sutures were placed, 1 at the edge of gross disease and another 1 cm distal from the first. After specimen removal and fixation, the distance between sutures and microscopic involvement of VIN was determined. RESULTS: Twenty-seven women were enrolled; however, only 19 had final fixed specimens that could be accurately measured. The median fixed distance of the vulvar margin was 0.85 cm (mean, 0.83; SD, 0.19) as compared to the gross, 1-cm margin (p = 0.001). Three subjects (16%) had microscopic involvement by VIN 3 in the grossly negative epithelium between the 2 sutures, but none had a positive peripheral margin. CONCLUSION: The gross surgical margin after vulvar resection is reduced by 15% when measured in its final fixed state, and a grossly negative 1-cm margin will seldom harbor significant disease.