A combined chemotherapy regimen of capecitabine and oxaliplatin given before chemoradiotherapy and surgery is well tolerated and shows promising anti-tumour activity and good overall survival rates in patients with poor-risk rectal cancer. The tumour response and survival reported in The Lancet Oncology compares favourably with previous studies of earlier stage rectal primary tumours, and further investigation of this intensive treatment is needed in randomised trials.

Patients with poor-risk rectal cancer are at a high risk of disease recurrence and poor survival despite standard chemoradiotherapy and optimum surgery. Combination chemotherapy is a standard treatment option for advanced disease and might improve the outcome for patients with poor-risk localised rectal cancer by reducing tumour size and limiting the spread of distant cancer.

To investigate the safety and long-term efficacy of neoadjuvant chemotherapy (capecitabine and oxaliplatin) before chemoradiotherapy and total mesorectal excision in patients with poor-risk rectal cancer, David Cunningham from the Royal Marsden Hospital, UK, and colleagues conducted a phase 2 trial.

High-resolution MRI was used to select 105 patients with poor-risk features who might benefit from the intensive treatment. Patients were given 12 weeks of capecitabine and oxaliplatin followed by chemoradiotherapy with capecitabine, and total mesorectal excision, and a further 12 weeks of postoperative capecitabine monotherapy. Pelvic MRI was repeated after the completion of chemotherapy and chemoradiotherapy to assess tumour response.

Findings showed high radiological response rates to preoperative treatment—74% (78/105) after neoadjuvant chemotherapy and 89% (93/105) after chemoradiotherapy. 95 patients were able to have total mesorectal excision, of whom 93 had microscopically clear resection margins, and 21 (20%) had pathological complete response (an absence of any detectable residual tumour cells within the resected specimen).

After 3 years, 68% of patients were progression-free, and overall survival was 83%. The 5-year overall survival of 75% compared favourably with rates shown in randomised trials of earlier stage rectal primary tumours (63–68%).

Additionally, the safety profile of the chemotherapy combination was similar to findings from randomised trials in advanced colorectal cancer, for which capecitabine and oxaliplatin is a well established treatment option.

The authors say: “Tumour downstaging was shown in most patients receiving neoadjuvant treatment with a low incidence of involved [circumferential resection margins (CRMs)] in the surgical specimens. Before treatment, 90% of eligible patients had tumours with CRMs at risk or involved.”

They conclude: “With no disease recurrences up to now in patients who achieved pathological complete response, this would be a valid end point to be used in future studies…our efficacy and safety findings justify further evaluation of neoadjuvant chemotherapy.”

Source: Lancet Oncology