Phase I–II Trial of Preoperative Chemoradiation in Locally Advanced Cervical Carcinoma

Abstract

Background. 5-Fluorouracil and cisplatin are characterized by in vitro synergism as well as radiosensitization. A phase I–II study was carried out on patients with invasive cervical carcinoma (FIGO IIB–IIIA) undergoing concomitant chemoradiation with 5-fluorouracil and cisplatin followed by radical surgery.Methods. Twenty-six patients of 53 years median age, 24 with IIB tumor and 2 with IIIA tumor, all with squamous carcinoma, entered the study. The chemoradiation protocol included external radiotherapy to the pelvis: 39.6 Gy (180 cGy/daily); 5-fluorouracil: 1 g/m2/daily, in continuous intravenous infusion days 1–4 and 27–30; cisplatin: 20 mg/m2/daily days 1–4 and 27–30. Four weeks after the end of chemoradiotherapy, patients underwent restaging and then radical surgery with pelvic and lumboaortic lymphadenectomy.Results. Twenty-six patients are evaluable for acute toxicity and 24 are evaluable for objective and pathologic response. Grade 3–4 thrombocytopenia or leukopenia was observed in 6 patients and grade 3 acute gastrointestinal toxicity in 3. After chemoradiation CR and PR were observed in 64 and 36% of cases, respectively (CR + PR = 100%). Two patients were excluded from surgery for other diseases. The remaining 24 patients were operated on; 23/24 patients showed negative section margins. The histology of the surgical specimen showed the absence of disease in 13 patients (54.2%), microscopic residual tumor in 4 patients (16.6%), residual disease ≤1 cm in 5 patients, and residual disease >1 cm in 2 patients. Median follow up was 33 months. Two-year actuarial local control was 91.7%.Conclusions. This study showed a particularly high rate of pathologic responses (complete + Tmic: 70.8%) and local control (2 years = 91.7%) in patients with advanced cervical cancer undergoing moderate doses of radiotherapy with concomitant chemotherapy followed by radical surgery.