Does administration of capecitabine and oxaliplatin both before and alongside radiotherapy improve cancer outcomes?

The authors evaluated the short term effectiveness and safety of capecitabine and oxaliplatin administered prior to and then alongside radiotherapy for high-risk locally advanced rectal cancer.

Although neoadjuvant (before surgery) chemoradiotherapy has signifcantly reduced the risk of local recurrence in locally advanced rectal cancer, system-wide failure remains an issue. Induction chemotherapy involves giving the patient doses of chemotherapy before neoadjuvant chemoradiotherapy (combination of chemotherapy and radiotherapy), but this remains controversial. There are worries that the long overall duration of chemotherapy that this would entail may lead to tumor spread in those who are not sensitive to chemotherapy.

The authors of this paper have adapted a new approach, combining the concept of induction chemotherapy and intensifed chemoradiotherapy with one cycle of the XELOX regimen administered prior to and two cycles of XELOX regimen administered alongside radiotherapy for high-risk locally advanced rectal cancer. The XELOX regimen involves the use of oxaliplatin (Eloxatin; inhibits DNA synthesis in cancer cells) and capecitabine (Xeloda; converted to compounds that inhibit DNA synthesis). The current study examined the safety and effectiveness of XELOX in patients with locally advanced rectal cancer.

42 patients were treated with a single cycle of XELOX (130 mg/m2 oxaliplatin on day 1, 1,000 mg/m2 capecitabine twice daily for 14 days, every 3 weeks) followed by two cycles of modified XELOX (100 mg/m2 instead of 130 mg/m2) alongside radiotherapy (50 Gy over 5 weeks). Patients subsequently underwent total mesorectal resection (surgical removal of the cancer plus a significant length of bowel either side).

7.1% of patients developed grade 3 (severe but not life threatening) radiation dermatitis (inflammation of the skin), 4.8% developed grade 3 hematological toxicity (toxicity of blood cells), 7.1% developed grade 3 proctitis (inflammation of the lining of the rectum) and 7.1% developed grade 3 diarrhea.

Grade 1 or 2 adverse effects (mild to moderate) were more common including anemia ( 16.7%; decrease in the amount of red blood cells), leucopenia (50%; decrease in the amount of white blood cells), thrombocytopenia (28.6%; decrease in the amount of platelets), nausea (42.9%), vomiting ( 31%), proctitis (76.2%), radiation dermatitis (95.2%), hand-foot syndrome (78.6%; redness, swelling, and pain on the palms of the hands and/or the soles of the feet) and peripheral neuropathy symptoms (95.2%; damage or disease of the nerves).

Average time from end of chemoradiation therapy to surgery was 60 days. 15% of patients obtained pathological complete response (no residual invasive tumor). 35% achieved a nearly pathological complete response (very few residual cancer cells) and 50% of patients achieved a moderate or minimal regression (disappearance of the tumor). 17.5% of patients had positive regional lymph nodes (lymph nodes tested positive for presence of cancer cells).

30% of patients were downstaged based on the size of the primary tumor (T staging). 20% of patients were downstaged based on the involvement of local lymph nodes (N staging). 37.5% had downstaging of both T and N stages. As a result, 87.5% of patients who underwent total mesorectal surgery had some sort of downstaging from neoadjuvant treatment.

The authors stated that the preliminary results suggest that induction chemotherapy followed by intensified concurrent chemoradiation with the XELOX regimen in patients with high-risk locally advanced rectal cancer are well tolerated and associated with favorable response and tumor downstaging.