According to research published early online in the Lancet Oncology, intensification of systemic therapy with neoadjuvant combination chemotherapy before standard treatment is feasible in poor-risk potentially operable rectal cancer, with acceptable safety and promising long-term outcomes.

In this phase II trial, researchers evaluated the safety and long-term efficacy of neoadjuvant chemotherapy with capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision in 105 rectal cancer patients. Patients received 12 weeks of neoadjuvant capecitabine and oxaliplatin (oxaliplatin 130 mg/m2 on day 1 with capecitabine 1000 mg/m2 twice daily for 14 days every 3 weeks) followed by chemoradiotherapy (54 Gy over 6 weeks) with capecitabine (825 mg/m2 twice daily), total mesorectal excision, and 12 weeks of postoperative adjuvant capecitabine (1250 mg/m2 twice daily for 14 days every 3 weeks). The primary endpoint was pathological complete response rate. The patients were followed up for a median of 55 months.

The following results were reported:
• Radiological response rates after neoadjuvant chemotherapy and chemoradiotherapy were 74% (78/105) and 89% (93/105), respectively.
• 97 patients underwent surgery, of whom 95 underwent total mesorectal excision, 93 had microscopically clear resection margins and 21 had pathological complete response (21/105 [20%]).
• 3-year relapse-free survival for patients who had complete resection was 74% (65—83).
• Following a protocol amendment for the exclusion of patients with pre-existing cardiac problems, one further thromboembolic event, comprising a fatal pulmonary embolism was observed.