• Oncology Clinical Trials
• Adjuvant/Neoadjuvant Therapy
• Radiology
• Reproductive Cancers

• Oncology Clinical Trials
• Oncology
• Adjuvant/Neoadjuvant Therapy
• Radiology
• Reproductive Cancers

Treatment with oxaliplatin plus 5-fluorouracil (5-FU) and radiation therapy (RT) before and after total mesorectal excision (TME) improved disease-free survival (DFS) in patients with locally advanced rectal cancer. Claus Rodel, MD, University of Frankfurt, Frankfurt, Germany, presented data from the Neoadjuvant Chemoradiotherapy and Adjuvant Chemotherapy With 5-Fluorouracil and Oxaliplatin Versus 5-Fluorouracil Alone in Rectal Cancer trial [CAO/ARO/AIO-04; NCT00349076; Rodel C et al. J Clin Oncol 2014].

Preoperative chemoradiotherapy (CRT) with TME and 5-FU-based adjuvant chemotherapy was established as the standard of care in patients with locally advanced rectal cancer by the CAO/ARO/AIO-94 trial [Sauer R et al. N Engl J Med 2004]. However, more effective therapy is needed. Previous Phase 1/2 trials demonstrated that oxaliplatin plus capecitabine and RT was a feasible, active treatment [Rodel C et al. J Clin Oncol 2007; Rodel C et al. J Clin Oncol 2003]. The purpose of this trial was to further evaluate CRT in patients with locally advanced rectal cancer.

In the Phase 3 CAO/ARO/AIO-04 trial, 1265 patients with locally advanced rectal cancer were randomly assigned to receive RT plus 5-FU and to continue 5-FU after TME (n=637) or to receive RT plus 5-FU and oxaliplatin followed by oxaliplatin, folinic acid, and 5-FU (mFOLFOX6) after TME (n=628). Patients were eligible for the trial if they had an Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 2, and histologically proven, advanced primary carcinoma of the rectum (tumor within 12 cm from the anal verge), with clinically staged T3/4 or any node-positive disease

The primary endpoint was DFS, and the main secondary endpoints were toxicity and compliance, R0 resection rate, pathologic complete response (pCR) and tumor regression, recurrence, and overall survival (OS). The baseline characteristics of patients were similar in both arms: median age 63.5 years, 71% male, and 77.5% with an ECOG PS of 0. Adjuvant chemotherapy after TME was initiated in 77.5% of patients; common reasons to not start adjuvant chemotherapy included postoperative complications, patient refusal, and disease progression. The median time interval between CRT and TME was 42 days in both arms.

In the intention-to-treat population, the addition of oxaliplatin to 5-FU and RT resulted in a significant increase in DFS over a follow-up period of 50 months (HR, 0.79; 95% CI, 0.64–0.98; p=0.030). The 3-year DFS rates were 75.9% in the 5-FU-only arm and 71.2% in the oxaliplatin arm; the 5-year DFS rates were 68.8% in the 5-FU-only arm and 64.3% in the oxaliplatin arm. A subgroup analysis suggested that the addition of oxaliplatin benefited patients regardless of age, gender, tumor stage, or nodal disease status. However, there was no significant difference in OS between the 2 arms (HR, 0.96; 95% CI, 0.72–1.26; p=0.752).

Overall, 20% and 24% of patients who received CRT with 5-FU or CRT with 5-FU and oxaliplatin experienced grade 3/4 adverse events. Common grade 3/4 adverse events included gastrointestinal, hematologic, genitourinary, and neurologic effects.

Prof. Rödel stated that the results from the CAO/ARO/AIO-04 trial suggest that the addition of oxaliplatin to 5-FU and RT before and after TME was well tolerated, increased the pCR rate, and improved DFS in patients with locally advanced rectal cancer.

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