Effective and safe neoadjuvant therapy to treat locally advanced rectal cancer

This study investigated the effectiveness and safety of pre-surgery combined chemotherapy with 5-fluorouracil and oxaliplatin (5-FU/OX) and radiotherapy in locally advanced rectal cancer (LARC). Researchers suggested that this combined treatment could be beneficial for LARC patients.  

The standard treatment for LARC patients is chemotherapy and radiation therapy (CRT) followed by rectal surgery. However, distant metastases (spread to other parts of the body) are still frequent (30-40% of these patients). Chemotherapy is used in these patients to reduce symptoms and prolong survival. Chemotherapy drugs attack cancer cells, slowing down cancer progression.

 5-fluorouracil (5-FU) chemotherapy has shown to be the most effective in these cases, with a complete tumor response rate between 5-20%. However, 5-FU has no effect on distant metastases. Prior studies showed that the addition of oxaliplatin (OX) to the treatment has a beneficial effect on survival of these patients, with a cost of a higher rates of negative side effects. Moreover, the 5-FU/OX combination reduced the metastasis rates. The treatment outcome and survival benefit of this combined treatment in LARC patients are still unclear.  

The objective of this study was to investigate the effectiveness and safety of the combined treatment with 5-FU/OX and radiotherapy followed by rectal surgery.

This study included 100 patients with stage 3 and 4 LARC with no distant metastasis. All patients were treated with 5-FU/OX chemotherapy and radiation therapy. 81% of the patients had lymph node metastasis at the time of diagnosis. The follow up was every 3 months for 2 years, then every 6 months thereafter.

Overall survival (OS; time from treatment to death by any cause) and disease-free survival (DFS; time from treatment to disease progression) were measured.  

After the end of CRT, 24% of patients had a complete tumor response (no sign of cancer). 97 patients underwent surgery.

The 2-year OS was 93.4% and the 5-year OS was 76.4%. The 5-year OS for patients with a complete tumor response was 95.7%. Patients with stage 3 cancer and younger patients (less than 65 years) were more likely to have better OS.

2-year DFS was 84.9% and 5-year DFS was 74.5%. The 5-year DFS was 95.7% for patients with complete tumor response. 9 patients experienced local recurrence (when the cancer comes back) and 23% presented with distant metastasis.    

All patients had toxicity associated with CRT. The severe toxicity rate was 17%. The most common CRT-related complication was fecal incontinence (in 15 patients; when feces leak unexpectedly from the rectum). The most common surgery-related complication was anastomotic fistula (in 5 patients; an abnormal connection between two areas of intestine).

This study reported that the combined 5-FU/OX chemotherapy and radiation therapy prior to rectal surgery could be beneficial for LARC patients with manageable side effects.