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CarPac Preop Chemoradiation Benefits Patients with Resectable Esophageal Cancer
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SAN FRANCISCO — After induction therapy, patients with resectable esophageal adenocarcinoma achieved superior pathological complete response with pre-operative carboplatin/paclitaxel based chemoradiation compared with oxaliplatin/capecitabine based chemoradiation, according to phase 2 study results presented at the Gastrointestinal Cancers Symposium.
“The main objectives of NEOSCOPE were to evaluate the toxicity and postoperative morbidity and mortality of [carboplatin/paclitaxel and oxaliplatin/capecitabine] based [neoadjuvant chemoradiotherapy] regimens,” Somnath Mukherjee, MD, from the department of oncology, CRUK/MRC Institute for Radiation Oncology, University of Oxford, said during his presentation. “We also wanted to demonstrate the feasibility of recruiting to our neoadjuvant chemoradiation trial in the UK where neoadjuvant chemotherapy is considered standard of care.”
Aiming to compare the toxicity and efficacy of two pre-operative chemoradiation regimens — carboplatin/paclitaxel (CarPac) vs. oxaliplatin/capecitabine (OXCAP) based chemoradiation — among patients with resectable esophageal adenocarcinoma (stage ≥ T3 and/or ≥ N1), Mukherjee and colleagues randomly assigned 85 patients (median age, 65 years; 81% men) from 17 centers in the UK to receive either regimen between October 2013 and February 2015.
The CarPac group received AUC2 carboplatin and 50 mg/m2 paclitaxel on days 1, 8, 15, 22 and 29, and the OXCAP group received 85 mg/m2 oxaliplatin on days 1, 15 and 29 and 625 mg/m2 capecitabine twice daily on days of radiation therapy. Both groups received concurrent radiation therapy (RT; 45 Gy/25 fractions/5 weeks), and induction chemotherapy (two cycles of OXCAP [oxaliplatin 130 mg/m2 D1, capecitabine 625 mg/m2 days 1-21, every 3 weeks). Surgeries were scheduled 6 to 8 weeks after neoadjuvant chemoradiotherapy.
“The primary endpoint of the study was the rate of pathological complete response,” Mukherjee said. “Secondary endpoints included feasibility of recruiting to our nCRT trial in the UK, the toxicity of the chemoradiation regimens, postoperative morbidity and mortality, and other efficacy parameters.”
Overall, 85% of patients had WHO Performance Status 0, 86% had T3 tumors, 67% had node positive disease, 84% had lower third or gastroesophageal junction tumors, and the median tumor length was 5.8 cm.
Pathological complete response was achieved in 11.9% of the OXCAP-RT group (13.9% of resected patients) compared with 27.9% of the CarPac-RT group (29.3% of resected patients).
Common Terminology Criteria for Adverse Events grade 3/4 toxicity rate during chemoradiotherapy was 42.1% for the OXCAP-RT regimen and 52.4% for the CarPac-RT regimen (P = .358).
In the OXCAP-RT group, 85.7% of patients underwent surgery compared with 95.3% in the CarPac-RT group; 30-day postoperative mortality was 2.8% and 2.4% respectively. “About half experienced any postoperative complications,” Muckherjee said.
“In conclusion, both OXCAP-RT and CarPac-RT were well tolerated regimens. The postoperative mortality was low. The rate of postoperative complications was similar to that reported in literature. Induction chemotherapy may have contributed to the unexpected high incidence of grade 3/4 neutropenia seen in the CarPac-RT arm. CarPac-RT passed the prespecified efficacy criteria for taking forward to a phase 3 trial. OxCap-RT failed to meet the same criteria,” he concluded. – by Adam Leitenberger
Reference:
Mukherjee S, et al. Abstract 03. Presented at: Gastrointestinal Cancers Symposium; Jan. 21-23, 2016; San Francisco.
Disclosure: Mukherjee reports consulting and advisory roles and receiving honoraria, research funding, travel accommodations and expenses from Celgene. Please see the abstract for a full list of all other researchers’ relevant financial disclosures.
Perspective
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Theodore S. Hong, MD
The NEOSCOPE trial evaluated induction capecitabine and oxaliplatin, followed by a randomization to concurrent capecitabine and oxaliplatin with radiation, vs. concurrent carboplatin and paclitaxel with radiation. This is an important evaluation, as capecitabine and oxaliplatin with radiation and carboplatin/paclitaxel with radiation have emerged as two of the more commonly used chemoradiation strategies for esophageal and GE junction cancer. The concept of using a fluoropyrimidine with oxaliplatin has really come to light with the publication of the PRODIGE trial, which showed that it was the same in efficacy as cisplatin and 5-FU but with substantially less toxicity, while the carboplatin and paclitaxel has gained acceptance based on the landmark CROSS trial, which demonstrated a survival benefit in the neoadjuvant setting for potentially resectable, locally advanced esophageal cancer.
However, no direct comparison has been done to this date regarding these two concurrent regimens. In looking at the outcomes from this trial, there is a suggestion that perhaps the use of carboplatin and paclitaxel was associated with a higher pathologic complete response rate and an improved R0 resection rate. However, there was more neutropenia seen with the use of carboplatin and paclitaxel when compared with capecitabine and oxaliplatin.
I think that these data are intriguing, but I think that the small numbers render a direct comparison difficult, and it remains difficult to declare a winner, as the small numbers lead to very wide variance in what the true pathologic complete response rate may be. One strategy that was employed by the ALLIANCE was evaluating the response based on PET scan to the induction chemotherapy and making a decision then, based on the PET response, as to whether one should continue regimens or switch regimens with the radiation phase. These results are eagerly anticipated.
In the meantime, I think that carboplatin and paclitaxel remains a very good, neoadjuvant chemotherapy strategy with radiation. Further evaluation of capecitabine and oxaliplatin – or what’s more commonly used in the United States, FOLFOX, using the infusion form rather than the oral form, will remain important for further evaluation.
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