A phase II study of weekly neoadjuvant chemotherapy followed by radical chemoradiation for locally advanced cervical cancer

Abstract

5586 Background: Chemoradiation (CRT) is the standard of care for locally advanced cervical cancer but survival is poor among women with large tumours, advanced stage, or positive nodes. Neoadjuvant chemotherapy (NACT) prior to CRT to down-stage tumours and lengthen the exposure to systemic treatment is designed to improve outcome. Methods: Patients (pts) with locally advanced cervical cancer received dose-dense carboplatin (AUC2) and paclitaxel (80 mg/m2) weekly, for 6 cycles, followed by CRT (external and brachytherapy) in week 7 with weekly cisplatin (40 mg/m2). The primary end-point was complete and partial response rate (RR) 12 weeks post CRT. Secondary objectives were RR for NACT at 6 weeks, toxicity and survival. The target RRs were 50% and 85% for NACT and post CRT (12-weeks) respectively. Results: Baseline characteristics were: median age at diagnosis 43 yrs (23–71); 74% squamous-, 20% adeno- and 6% adenosquamous carcinomas; FIGO stage IB2 (11%), II (50%), III (33%), IV (6%). The trial closed in Oct 08 with 46 pts. Of the first 36 pts enrolled 9 failed to complete protocol therapy (7 did not complete 6 NACT cycles, 2 did not complete the pre-specified minimum of 4 cycles of concomitant cisplatin). Using data currently available, the RR associated with NACT is 72% (95% CI 53–86%), and 81% at 12 weeks (95% CI 63–92%). Nonhaematological grade 3/4 toxicity was rare (<5%). There was grade 2 alopecia in 25% pts. Grade 3 and 4 haematological toxicity was seen in 10% and <3% of pts respectively. Updated results, including survival, will be presented for all pts. Conclusions: Dose-dense weekly NACT chemotherapy with carboplatin and paclitaxel followed by radical CRT is associated with a high response rate and is feasible. This approach merits further investigation in a phase III trial. [Table: see text]

Treatment Outcome and Toxicity of Neoadjuvant Chemotherapy Followed by Concomitant Chemoradiotherapy Versus Concomitant Chemoradiation Alone in Locally Advanced Cervical Carcinoma: A Comparative Study

“…The overall response rates (CR+PR) in Arm 1 (chemoradiation alone arm) and Arm 2 (neoadjuvant chemotherapy followed by chemoradiation arm) were 96% and 100%, respectively (complete response rates of 73.33% and 75%, respectively, and the partial response rates of 23.33% and 25%, respectively). The results were, therefore, similar to the reported literature [9,10]. The complete response rate was 87% and 97% in the chemoradiation alone arm and neoadjuvant followed by the definitive chemoradiation arm, respectively.…”

“…concerning the use of neoadjuvant chemotherapy in this setting. In one study [10], the complete response rates noted were 97% and 87% in the neoadjuvant group and the chemoradiation group, respectively. There were no differences in overall survival between the two arms.…”

“…The main limitations of these earlier studies were that the comparisons were made relative to radiation alone and not concurrent cisplatin-based chemoradiation which at present, which is the standard of treatment. Neoadjuvant chemotherapy followed by concurrent chemoradiation has been compared to concurrent chemoradiation alone (which is the present standard of care) in locally advanced carcinoma of the cervix, which showed encouraging results for the use of neoadjuvant chemotherapy [9][10]. However, there are little data to believe that adding neoadjuvant chemotherapy might result in better tumor control, leading to increased overall survival than with concurrent chemotherapy alone with added risks of slightly enhanced toxicity.…”

Neoadjuvant chemotherapy with weekly cisplatin and paclitaxel followed by chemoradiation for locally advanced cervical cancer

“…Trials using short cycle chemotherapy with a chemotherapy cycle length of < 14 days and cisplatin dose intensities ≥ 25 mg/m 2 per week appear to be associated with an improvement in survival compared with those using a more prolonged cycle interval [6]. The initial results from two phase II studies [9,10] have been reported on patients who received NACT using weekly paclitaxel (60-80 mg/m 2 ) and carboplatin (AUC = 2) for 6 weeks followed by CCRT. Following NACT, a response rate of 67.8-72.7% was achieved, mostly partial responses.…”

“…Traditional triweekly (once every 3 weeks) regimens of NACT followed by CCRT may not be superior to CCRT alone for the treatment of LACC [6][7][8]. Weekly regimens of NACT followed by CCRT may be superior to CCRT alone [6,9,10]. Moreover, particularly in developing countries, the incidence of advanced cervical cancer is high, and access to radiotherapy facilities is limited [11].…”