Carboplatin/Paclitaxel Tops Oxaliplatin/Capecitabine as Neoadjuvant Regimen for Esophageal Cancer

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Both OxCap/RT and CarPac/RT were well-tolerated regimens. Postoperative mortality was low, and the rate of postoperative complications was similar to the reported literature.

Somnath Mukherjee, MD

The United Kingdom’s phase II ­NEOSCOPE trial compared the toxicity and efficacy of two preoperative chemoradiation regimens—carboplatin/paclitaxel and oxaliplatin/capecitabine—and judged one to be the winner.

“CarPacRT passed the prespecified efficacy criteria for taking forward to phase III, but OxCapRT failed to meet the same criteria,” according to Somnath Mukherjee, MD, of the University of Oxford, United Kingdom, who presented his findings at the 2016 Gastrointestinal Cancers Symposium.

He was referring to chemoradiotherapy with carboplatin/paclitaxel ­(CarPacRT) and chemoradiotherapy with oxaliplatin/capecitabine ­(OxCapRT), which were compared in a 17-center study of 85 patients with esophageal or gastroestophageal junction cancer stage ≥ T3 and/or N1.1 Most patients (86%) had stage T3 tumors and one to three positive nodes.

Neoadjuvant regimens that include weekly carboplatin/paclitaxel and oxaliplatin/fluoropyrimidine have shown promising activity in clinical trials, he noted.

‘Pick a Winner’ Design

“Our study had a ‘pick a winner’ design,” Dr. Mukherjee said, explaining that the study’s primary endpoint was pathologic complete response, and the regimen achieving the highest rates would probably be further evaluated.

“A [pathologic complete response] of 15% was not considered large enough to warrant further investigation, while a pathologic complete response of 35% was considered worthwhile,” he continued. The researchers decided that a treatment arm with fewer than 10 pathologic complete responses achieved would not be taken forward to a phase III trial.

“Ten of the first 38 patients in the ­CarPacRT arm attained a pathologic complete response, therefore meeting our prespecified criteria of success,” Dr. Mukherjee reported. Rates of pathologic complete response were 27.9% after chemoradiotherapy with carboplatin/paclitaxel and 11.9% after chemoradiotherapy with oxaliplatin/capecitabine, he noted.

Regimen Details

As neoadjuvant treatment, both arms received induction chemotherapy with two cycles of oxaliplatin at 130 mg/m2 on day 1 and capecitabine at 625 mg/m2 on days 1–21 every 3 weeks. Patients then received one of these two regimens:

Oxaliplatin at 85 mg/m2 on days 1, 15, and 29 plus capecitabine at 625 mg/m2 twice daily on the days of radiotherapy (Monday through Friday);

Carboplatin at area under the curve (AUC) of 2 plus paclitaxel at 50 mg/m2 once weekly.

Chemotherapy was given concurrently with radiotherapy at 45 Gy in 25 fractions for 5 weeks, under a pretrial and on-trial radiotherapy quality assurance program. Patients underwent surgery 6 to 8 weeks after chemoradiotherapy.

Surgery was completed by 36 of 42 patients (86%) in the chemoradiotherapy with oxaliplatin/capecitabine arm and by 41 of 43 patients (95%) in the chemoradiotherapy with carboplatin/paclitaxel arm. Full-dose radiotherapy was received by 38 and 41 patients, respectively. Dose intensity was somewhat higher in the chemoradiotherapy with oxaliplatin/capecitabine arm.

Rates of R0 resection (in those who underwent surgery) were 72.2% in the chemoradiotherapy with oxaliplatin/capecitabine arm and 80.5% in the chemoradiotherapy with carboplatin/paclitaxel arm. R1 resections were noted in 27.8% and 19.5%, respectively.

Both Regimens Well Tolerated

Grade 3–5 treatment-related toxicities were observed in about 32% of all patients during induction, in 42% of patients receiving chemoradiotherapy with oxaliplatin/capecitabine and in 52% of patients receiving chemoradiotherapy with carboplatin/paclitaxel. The only difference between the arms was more neutropenia with carboplatin/paclitaxel plus radiotherapy (21.4% vs 2.6%; P = .011). By postoperative day 30, the rate of complications was approximately 50% per arm.

“Induction chemotherapy may have contributed to the unexpected high incidence of grade 3–4 neutropenia seen in the CarPacRT arm,” he said. “Both OxCap/RT and CarPac/RT were well-tolerated regimens. Postoperative mortality was low, and the rate of postoperative complications was similar to the reported literature.”

The study was led by Tom Crosby, MBBS, Velindre Hospital, Cardiff, and funded by Cancer Research UK. ■

Disclosure: Dr. Mukherjee has received honoraria and research funding from as well as served as a consultant or advisor to Celgene.


1. Mukherjee S, Hurt C, Gwynne S, et al: NEOSCOPE. 2016 Gastrointestinal Cancers Symposium. Abstract 3. Presented January 21, 2016.

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