Weekly Cisplatin vs. Triweekly Docetaxel Plus Cisplatin With Concurrent Chemoradiation in Post-Operative Treatment for Cervical Cancer With High-Risk Pathological Factors: A Randomized Controlled Phase III Trial From a Single Institution

Abstract

After radical surgery, patients with high-risk factors were recommended adjuvant concurrent chemoradiation (CCRT). Cisplatin and cisplatin-based combination chemotherapy were the most common concurrent chemotherapy in previous studies. However, there are still few randomized controlled studies comparing which is better for survival. We conduct this prospective study to compare triweekly combination chemotherapy with weekly cisplatin chemoradiation in adjuvant radiation for cervical cancer patients with high-risk factors after radical surgery.Patients aged 18-70 years early-stage cervical cancer with high-risk pathological factors (adenocarcinoma/adenosquamous carcinoma, parametrial invasion, positive surgical margins, and lymph node metastasis) after radical hysterectomy were included and randomized 1:2 to the DDP group and DP group. The DDP group received chemotherapy with weekly cisplatin (40 mg/m2) of 5 cycles concurrent with radiation. The DP group received a triweekly regimen of cisplatin (75 mg/m2) plus docetaxel (75 mg/m2) of 4 cycles and the first cycle was initiated within 1-2weeks after surgery. Radiotherapy was started concurrently at the second cycle of chemotherapy in DP group. The primary end point was the rate of disease-free survival (DFS) at 5 years.A total of 268 patients were included in the analysis (91 in the DDP group, 177 in the DP group). The median follow-up period is 54 months (2-90m), and 2 cases were lost to follow-up. Baseline demographic and disease characteristics were balanced among the treatment groups. In the intention-to-treat population, 5-year DFS showed a better trend in DP group than DDP group, although there was no statistically significant difference (85.9% vs 78.0%; HR 1.64; 95% CI, 0.91-2.95, P = 0.096). There was no difference in 5-year OS, DMFS and LRFS between the groups (87.0%, 87.6% and 97.2% for DP group; 79.1%, 82.4% and 94.5% for DDP group, P = 0.127, 0.249 and 0.253, respectively). Distant metastasis was the major pattern of treatment failure and occurred in 37 patients (23 in DP group and 14 in DDP group). Lymph nodes (15/37), lung (9/37), liver (5/37), and bone (7/37) were the most common sites of metastasis. Forty-two patients died, of which 3 died from other causes (1 for cardiac, 1 for renal, and 1 for a second primary tumor). 142(80.2%) patients in DP group and 84(92.3%) patients in DDP group completed the treatment according to protocol. Toxic reactions are most common in hematology and intestinal tract. The incidence of severe acute hematological was significantly higher in the DP group than in the DDP group (47.6% vs 21.8%, P = 0.000), but there was no significant difference in severe intestinal reactions.Compared with weekly cisplatin, tri-weekly combined cisplatin plus docetaxel showed a tendency to improve survival in cervical cancer with pathological high-risk factors, but the difference was not statistically significant. Clinical trials.gov identifier NCT01999933.