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Chemotherapy before surgery for colon cancer may improve survival, study shows

BMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e7487 (Published 06 November 2012) Cite this as: BMJ 2012;345:e7487
  1. Susan Mayor
  1. 1London

Chemotherapy before surgery for locally advanced colon cancer significantly shrinks tumours, making them easier to remove and potentially reducing the risk of recurrence, shows a pilot study.1

Treating patients with other cancers of the digestive system with chemotherapy for several weeks before surgery is already standard practice, after trials showed that this prolonged survival. But the strategy had been considered too risky for colon cancer, because if tumour cells failed to respond and continued growing this could cause a potentially fatal blockage of the colon. It has also been difficult to determine which patients might benefit from preoperative chemotherapy.

The UK researchers randomly assigned 150 patients with locally advanced colorectal tumours to preoperative chemotherapy with three cycles of oxaliplatin, l-folinic acid, and fluorouracil at two weekly intervals before surgery. This was followed by a further nine cycles of chemotherapy. The control group received standard postoperative chemotherapy. The researchers used a computed tomography risk algorithm that was based on the depth of tumour invasion beyond the muscularis propria to determine which patients would be suitable for preoperative chemotherapy.

Results for the primary outcome measures of feasibility and safety showed that 89% of the patients (85 of 95) starting preoperative chemotherapy completed it; only 7% of the patients had grade 3-4 gastrointestinal toxicity. All 99 tumours in the preoperative chemotherapy group were resected; and no significant differences in postoperative morbidity were shown between this group and the control group.

Preoperative chemotherapy significantly downstaged patients’ tumours in comparison with chemotherapy after surgery (P=0.04). Nearly a third (29 of 94) of the patients’ tumours shrank significantly with chemotherapy before surgery, whereas only 2% (one of 46) shrank in the control group. Two patients showed complete pathological responses with preoperative chemotherapy, meaning that their tumours completely disappeared.

“These feasibility results show that preoperative chemotherapy can be delivered safely and efficiently, paving the way for a larger phase III study which, if successful, could completely change the way we treat colon cancer within five years,” said Dion Morton, director of the Birmingham Experimental Cancer Medicine Centre at the University of Birmingham and lead investigator of the Cancer Research UK funded study.

“Shrinking the tumours beforehand makes them easier to remove, reducing the chances of any of the tumour being left behind,” explained Morton. “Importantly, all of the patients we treated in this way were well enough to proceed with their surgery, and they were no more likely to have complications that extended their hospital stay afterwards.”

The study also randomised patients with KRAS wild type tumours to receive the epidermal growth factor receptor inhibitor panitumumab before surgery or not. Results showed that it was feasible to obtain results of genetic testing of patients’ tumours within eight days, which was short enough to enable them to be treated before surgery.

The research group considered the pilot study findings encouraging enough to proceed with a larger phase III trial to assess the effects of preoperative chemotherapy on survival. As well as continuing to follow up the 150 patients studied so far, they plan to recruit at least a further 900 patients. “If preoperative therapy results in fewer recurrences, as well as tumour downstaging, the established pathway of surgery then chemotherapy in the management of colon cancer could potentially change,” they concluded.

In an editorial accompanying the pilot study results,2 Andrés Cervantes of the University of Valencia, Spain, said that although the findings were encouraging, preoperative chemotherapy should not be considered a standard option for locally advanced colon cancer until the final results from the full trial are reported. But he predicted that “preoperative chemotherapy should induce not only tumour downstaging but a significant prolongation of disease free survival and eventually better survival.”

Notes

Cite this as: BMJ 2012;345:e7487

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