Paclitaxel plus fluorouracil did not show overall survival superiority compared with paclitaxel plus cisplatin or paclitaxel plus carboplatin in definitive chemoradiation in patients with locally advanced esophageal squamous cell carcinoma (ESCC), according to study results published in JAMA Network Open.

The phase 3, open-labeled, randomized ESO-Shanghai 2 phase III clinical trial (ClinicalTrials.gov Identifier: NCT02459457) was conducted in 11 centers in China. Eligible participants had histologically confirmed ESCC, stage IIa to IVa disease; no previous treatment; were aged 18 to 75 years; Eastern Cooperative Oncology Group performance status of 2 or lower; no severe abnormalities in hematopoietic, cardiac, pulmonary, kidney, or hepatic function; and adequate hematologic function.

The patients were randomly assigned 1:1:1 to the paclitaxel plus fluorouracil, cisplatin, or carboplatin treatment groups. All patients received concurrent chemoradiotherapy and then consolidation chemotherapy. The first fraction of radiotherapy and first cycle of chemotherapy started on the same day. Participants received the same radiotherapy regimen with photons (≥6 mV) for a total dose of 61.2 Gy in 34 fractions. The primary endpoint was overall survival.


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A total of 321 patients with esophageal cancer were enrolled from July 1, 2015, to February 26, 2018. The median (IQR) age was 63.0 (59-67), 65.0 (59-69), and 64.0 (60-68) years in the fluorouracil, cisplatin, and carboplatin groups, respectively. The median (IQR) follow-up was 46.0 (36.6-53.0) months at the time of analysis on August 31, 2020.

The 1-, 2-, and 3-year overall survival rates were 79.4% (71.8%-87.0%), 62.6% (53.4%-71.8%), and 57.2% (47.6%-66.8%), respectively, for the fluorouracil group; 81.3% (73.9%-88.7%), 66.7% (57.7%-75.7%), and 60.1% (50.5%-69.7%), respectively, for the cisplatin group; and 79.4% (71.8%-87.0%), 60.5% (51.3%-69.7%), and 56.5% (47.1%-65.9%), respectively, for the carboplatin group.

Fluorouracil did not demonstrate overall survival superiority vs the cisplatin or carboplatin regimens (fluorouracil vs cisplatin: hazard ratio [HR], 1.06; 95% CI, 0.71-1.60; P =.77; fluorouracil vs carboplatin: HR, 0.94; 95% CI, 0.63-1.40; P =.77).

Higher rates of acute grade 3 or 4 hematologic toxic effects were observed in the cisplatin group, including neutropenia (69 events [60.8%] vs 19 [17.8%] for fluorouracil and 37 [34.6%] for carboplatin; P <.001), thrombocytopenia (14 events [13.1%] vs 4 [3.7%] for fluorouracil and 5 [4.7%] for carboplatin; P =.01), and gastrointestinal toxic effects, such as grade 2 or higher vomiting (17 events [15.9%] vs 3 [2.8%] for fluorouracil and 5 [4.7%] for carboplatin; P <.001).

The fluorouracil group had a higher proportion of patients with late esophagitis vs the cisplatin or carboplatin groups (17 events [15.9%] vs 8 [7.5%] for cisplatin and 6 [5.6%] for carboplatin; P =.03).

The researchers noted that their analysis did not include quality of life and a noninferiority study design. Also, a total dose of 61.2 Gy was delivered instead of the 50.4 Gy dose commonly administered in Western countries.

“Because different regimens may lead to different adverse effects in patients treated with concurrent chemoradiotherapy for locally advanced esophageal cancer, these results suggest that specialists have more choices in clinical practice and for future research that can account for the needs of patients, without sacrificing odds of survival,” the study authors commented.

Reference

Ai D, Ye J, Wei S, et al. Comparison of 3 paclitaxel-based chemoradiotherapy regimens for patients with locally advanced esophageal squamous cell cancer: a randomized clinical trial. JAMA Netw Open. Published online February 21, 2022. doi:10.1001/jamanetworkopen.2022.0120