NEOADJUVANT CARBOPLATIN AND PACLITAXEL FOLLOWED BY RADICAL HYSTERECTOMY AND ADJUVANT CISPLATIN CHEMORADIATION: PHASE II STUDY EVALUATION OF MULTIMODALITY TREATMENT FOR LOCALLY ADVANCED CERVICAL CANCER

Abstract

Aim: In order to treat locally advanced cervical carcinoma, our goal was to assess the effectiveness and safety of neoadjuvant chemotherapy, radical hysterectomy, postoperative radiation, and biweekly cisplatin. Materials and Method: Radical type III hysterectomy, adjuvant radiation therapy, and 6-weekly doses of cisplatin at 35 mg/m2 were given to 40 patients staged as IB2-IIIB over the period of three 20-day courses of carboplatin (area under the time plot: 5 mg/min/ml) and paclitaxel (at 170 mg/m2 by 2-h infusion both on day 2). Evaluations were made of response rate, resectability, toxicity, and lifespan. Result: There were 40 patients enrolled. Each was assessed for toxicity and responsiveness to neoadjuvant chemotherapy. 100 courses in total were given out. 94% of patients had clinical responses, with a 94% confidence range (CI) of 89.1% to 99%. 8% of the work is finished, while 85% is incomplete. The pathologically complete or nearly complete responses were observed in 16% and 19% of the 40 patients who underwent surgery (resectability: 94%); positive surgical boundaries were identified in 11% of the patients, and positive pelvic lymph nodes were seen in 19% of the patients. Adjuvant chemoradiation was scheduled for 25 patients. A median of 4 cisplatin treatments were administered together with a mean dose of 49.2 Gy over the course of 42.7 days (range, 32–60). The average brachytherapy dose was 30 Gy (range 25.4–35.4). Neutropenia grades 3 and 4 were well tolerated with neoadjuvant therapy in 11% and 2% of the courses, respectively. Adjuvant chemoradiation generally caused grade 1/2 haematological and gastrointestinal toxicity. 35 patients in all completed the entire course of therapy. The estimated overall survival in the intention-to-treat study was 78% (94% CI 61% to 87%) at a median follow-up of 20 months (range 2–25). Neutropenia grades 3 and 4 were well tolerated with neoadjuvant therapy in 11% and 2% of the courses, respectively. Adjuvant chemoradiation generally caused grade 1/2 haematological and gastrointestinal toxicity. Thirty patients in total received the full course of therapy. The estimated overall mortality in the purpose study was 78% (94% CI 61% to 87%) at a median follow-up of 20 months (range 2–25). Conclusion: The combination of neoadjuvant chemotherapy, radical hysterectomy, and adjuvant radiotherapy in addition to cisplatin is a highly effective and tolerable approach for locally advanced cervical cancer.