Safety of paclitaxel-based regimens varies among patients with esophageal cancer
Click Here to Manage Email Alerts
Paclitaxel plus fluorouracil did not demonstrate OS superiority over paclitaxel plus cisplatin or paclitaxel plus carboplatin in definitive chemoradiation for locally advanced esophageal squamous cell carcinoma.
The results of the randomized, multicenter phase 3 clinical trial, published in JAMA Network Open, also showed higher rates of hematologic and gastrointestinal toxicities among those who received cisplatin.
"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,” Kuaile Zhao, MD, professor in the department of radiation oncology at Fudan University Shanghai Cancer Center, and colleagues wrote.
Methodology
The analysis included 321 patients (median age, 64 years; interquartile range, 59-69; 77.3% men) with previously untreated stage IIA to stage IVA esophageal squamous cell carcinoma at 11 cancer centers in China between July 1, 2015, and Feb. 26, 2018. Zhao and colleagues randomly assigned patients 1:1:1 to groups combining paclitaxel with fluorouracil, cisplatin or carboplatin. Radiotherapy for all patients consisted of 61.2 Gy delivered in 34 fractions.
The cisplatin group (n = 107; 76.6% men; 54.2% aged 65 years or older) received two cycles of concurrent chemoradiotherapy, followed by two cycles of consolidation chemotherapy with monthly paclitaxel plus cisplatin. The fluorouracil group (n = 107; 74.8% men; 61.7% aged 65 years or older) received six cycles of weekly paclitaxel plus fluorouracil in concurrent chemoradiotherapy followed by two cycles of monthly paclitaxel plus fluorouracil in consolidation chemotherapy. The carboplatin group (n = 107; 80.4% men; 58.9% aged 65 years or older) received six cycles of weekly paclitaxel plus carboplatin in concurrent chemoradiotherapy, followed by two cycles of monthly paclitaxel plus carboplatin in consolidation chemotherapy.
OS served as the primary endpoint; secondary endpoints included PFS and adverse events.
Key findings
After median follow-up of 46 months (interquartile range, 36.6-53), researchers reported a 3-year OS rate of 57.2% in the fluorouracil group, 60.1% in the cisplatin group and 56.5% in the carboplatin group (fluorouracil vs. cisplatin, HR = 1.06; 95% CI, 0.71-1.6; fluorouracil vs. carboplatin, HR = 0.94; 95% CI, 0.63-1.4).
The cisplatin group experienced higher incidence of acute grade 3 or grade 4 adverse events, including:
- neutropenia — 69 events (60.8%) compared with 19 (17.8%) for fluorouracil and 37 (34.6%) for carboplatin;
- thrombocytopenia — 14 events (13.1%) compared with four (3.7%) for fluorouracil and five (4.7%) for carboplatin;
- anemia — 50 events above grade 2 (46.7%) vs. 25 (23.4%) for fluorouracil and 37 (34.6%) for carboplatin;
- fatigue — 11 events (10.3%) compared with two (1.9%) for fluorouracil and one (0.9%) for carboplatin; and
- vomiting — 17 events above grade 2 (15.9%) vs. three (2.8%) for fluorouracil and five (4.7%carb) for oplatin.
“The weekly fluorouracil or carboplatin plans were accompanied by relatively mild toxic effects while the monthly cisplatin regimen led to higher rates of hematologic and gastrointestinal toxic effects,” Zhao and colleagues wrote.
Collapse
Read more about
Click Here to Manage Email Alerts