Preoperative chemotherapy in patients with intermediate-risk rectal adenocarcinoma selected by high-resolution magnetic resonance imaging: the GEMCAD 0801 Phase II Multicenter Trial

Abstract

Background: The need for preoperative chemoradiation or short-course radiation in all T3 rectal tumors is a controversial issue. A multicenter phase II trial was undertaken to evaluate the efficacy and safety of neoadjuvant capecitabine and oxaliplatin combined with bevacizumab in patients with intermediate-risk rectal adenocarcinoma.

Methods: We recruited 46 patients with T3 rectal adenocarcinoma selected by magnetic resonance imaging (MRI) who were candidates for (R0) resection located in the middle third with clear mesorectal fascia and who were selected by pelvic MRI. Patients received four cycles of neoadjuvant capecitabine and oxaliplatin combined with bevacizumab (final cycle without bevacizumab) before total mesorectal excision (TME). In case of progression, preoperative chemoradiation was planned. The primary endpoint was overall response rate (ORR).

Results: On an intent-to-treat analysis, the ORR was 78% (n = 36; 95% confidence interval [CI]: 63%-89%) and no progression was detected. Pathologic complete response was observed in nine patients (20%; 95% CI: 9-33), and T downstaging was observed in 48%. Forty-four patients proceeded to TME, and all had R0 resection. During preoperative therapy, two deaths occurred as a result of pulmonary embolism and diarrhea, respectively, and one patient died after surgery as a result of peritonitis secondary to an anastomotic leak (AL). A 13% rate of AL was higher than expected. The 24-month disease-free survival rate was 75% (95% CI: 60%-85%), and the 2-year local relapse rate was 2% (95% CI: 0%-11%).

Conclusion: In this selected population, initial chemotherapy results in promising activity, but the observed toxicity does not support further investigation of this specific regimen. Nevertheless, these early results warrant further testing of this strategy in an enriched population and in randomized trials.

Trial registration: ClinicalTrials.gov NCT00909987.

Conflict of interest statement

Disclosures of potential conflicts of interest may be found at the end of this article.

©AlphaMed Press; the data published online to support this summary is the property of the authors.

Figures

Figure 1.

Radiological and pathological response. T downstaging defined as lower pathologic T stage compared with the pretreatment mrT stage. N downstaging defined as N negative pathologic stage compared with mrN positive at baseline. a15 ypN negative of 29 mrN positive at baseline. bDefined as intact mesorectum with only minor irregularities. Abbreviations: CRM, circumferential resection margin; ITT, intention to treat; MRI, magnetic resonance imaging; mr, magnetic resonance; pCR, pathological complete response; TME, Total mesorectal excision; TRG, tumor regression grade.