Gabriella Ferrandina1, Giacomo Corrado2, Giuseppe Vitrano3, Valerio Gallotta1, Eleonora Palluzzi1, Mariagrazia Distefano1, Giovanni Scambia1. 1. Gynecologic Oncology Unit, Department of Women and Children Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy. 2. Gynecologic Oncology Unit, Department of Women and Children Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy. giacomo.corrado@alice.it. 3. Department of Obstetrics and Gynecology, Hospital "Paolo Giaccone", Palermo, Italy.
Abstract
PURPOSE: The role of dose-dense schedules in the neo-adjuvant treatment (NACT) of locally advanced cervical cancer (LACC) has been reported. This phase II study investigated activity of dose-dense paclitaxel/platinum before radical surgery (RS) in LACC patients. METHODS: The primary end-point was the rate of optimal pathological response (OPR: pathological complete/microscopic response). NACT (paclitaxel: 80 mg/m2) and carboplatin (AUC 2) were administered for 6 weeks. Overall response rate (ORR) to NACT was assessed by the RECIST criteria. Patients amenable to surgery were triaged to RS. The null hypothesis was that the OPR rate would improve from 30.0 to 45.0% (α error: 0.05, β error: 0.2). The regimen would be considered active if > 25 OPRs were found. RESULTS: 36 patients were enrolled; 19 patients were stage IIB (52.8%) and 16 (44.4%) patients had pelvic lymph-node involvement at imaging. All patients completed neo-adjuvant chemotherapy; ORR was of 75.0%. RS was performed in 29 (93.5%) patients. Since the OPR was 16.1%, we evaluated the real chances to achieve the number of OPR required by the Simon design and decided to close the study. Grade 3/4 hematological toxicity occurred in 5 patients; surgical morbidity occurred in 14 patients. The 2-year PFS rate was 69.0%. CONCLUSION: Dose-dense neo-adjuvant paclitaxel/carboplatin is feasible and safe in LACC patients; however, failure to achieve the primary end-point has to be recognized. Given the heterogeneity of the available studies, robust data from an adequately sized prospective study focused on more homogeneous series are required.
PURPOSE: The role of dose-dense schedules in the neo-adjuvant treatment (NACT) of locally advanced cervical cancer (LACC) has been reported. This phase II study investigated activity of dose-dense paclitaxel/platinum before radical surgery (RS) in LACC patients. METHODS: The primary end-point was the rate of optimal pathological response (OPR: pathological complete/microscopic response). NACT (paclitaxel: 80 mg/m2) and carboplatin (AUC 2) were administered for 6 weeks. Overall response rate (ORR) to NACT was assessed by the RECIST criteria. Patients amenable to surgery were triaged to RS. The null hypothesis was that the OPR rate would improve from 30.0 to 45.0% (α error: 0.05, β error: 0.2). The regimen would be considered active if > 25 OPRs were found. RESULTS: 36 patients were enrolled; 19 patients were stage IIB (52.8%) and 16 (44.4%) patients had pelvic lymph-node involvement at imaging. All patients completed neo-adjuvant chemotherapy; ORR was of 75.0%. RS was performed in 29 (93.5%) patients. Since the OPR was 16.1%, we evaluated the real chances to achieve the number of OPR required by the Simon design and decided to close the study. Grade 3/4 hematological toxicity occurred in 5 patients; surgical morbidity occurred in 14 patients. The 2-year PFS rate was 69.0%. CONCLUSION: Dose-dense neo-adjuvant paclitaxel/carboplatin is feasible and safe in LACC patients; however, failure to achieve the primary end-point has to be recognized. Given the heterogeneity of the available studies, robust data from an adequately sized prospective study focused on more homogeneous series are required.