A phase II study of dose-dense neoadjuvant chemotherapy with weekly paclitaxel and carboplatin followed by chemoradiation in locally advanced cervical carcinoma.

Abstract

5104 Background: We prospectively studied dose dense neoadjuvant chemotherapy (NACT) designed for an enhanced cell kill, better local control and eradication of micrometastases prior to standard concurrent chemoradiation (CRT) in locally advanced cervical cancer. Methods: Between June 2010 and December 2011, 21 patients (median age - 51 years, range 35 - 67) of cervical cancer with locally advanced disease received NACT using paclitaxel (60mg/m2) and carboplatin (AUC-2) weekly for 6 doses. Patients (pts) then received concurrent CRT (external and brachytherapy) with weekly cisplatin (40mg/m2 for 6 doses) at a mean interval of 15 days (range 7–20 days). The primary end-point was response rate i.e. complete response (CR) and partial response (PR) 12 weeks post CRT. Results: Baseline stages were: stage 2A - 19%, 3B - 71.4%, 4A - 9.5%. Squamous cell carcinoma and adenocarcinoma constituted 95.2% and 4.7% pts respectively. Following NACT, 66.6% pts responded (CR -9.5% %; PR – 57.1 %), 23.8% had stable disease (SD) and 4.7% had progressive disease (PD). A total of 18 pts completed NACT and CRT of which 17 were in CR and 1 in PR. One patient with stage 4A disease developed vesicovaginal fistula at end of NACT for which she underwent pelvic exenteration and was in pathological CR. After NACT, one patient developed choroid metastases and was taken off study protocol while another patient was lost to follow up. At a mean follow up 5.8 months (range 1 - 14), 90% pts were in CR, 5% in PR and 5% had PD. During NACT, Grade 3/4 neutropenia, thrombocytopenia and anemia were seen in 33.3%, 4.7% & 9.5% of pts, respectively and grade 3/4 non-hematological toxicities in 9.5% pts. Following CRT, Grade 3/4 neutropenia, thrombocytopenia and anemia were seen in 25%, 5% and 10% of pts, respectively while 20% pts had grade 3/4 non-hematological toxicities. G-CSF was used in 30% pts during NACT and 25% pts during CRT, respectively. Conclusions: NACT with weekly paclitaxel and carboplatin followed by radical CRT is feasible and is associated with a high response rate in locally advanced cervical cancer. This approach needs to be studied in a phase III trial.