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Published on 26 November 2009

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Tumour shrinkage leads to more curative surgery

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An article in The Lancet Oncology reports that adding cetuximab to neoadjuvant chemotherapy can shrink tumours

More than half of all patients with colorectal cancer develop metastatic disease. It most commonly occurs in the liver.

Surgical removal of colorectal liver metastases (CLM) is potentially curative. However, about 80 percent of patients with CLM have inoperable disease and poor prognosis at presentation.

Earlier research indicates that neoadjuvant treatment with irinotecan or oxaliplatin-based chemotherapy can shrink tumours. This consequently makes surgery possible.

Most colorectal cancers express epidermal growth factor receptor (EGFR). The high levels of EGFR are linked to more metastases and poorer outcome.

Cetuximab is a monoclonal antibody that targets and disables EGFR. It has been proven to prevent cancer cell growth. The use of this drug might increase the effectiveness of chemotherapy in patients with CLM.

Gunnar Folprecht, from University Hospital Carl Gustav Carus, Dresden, Germany, and colleagues from Germany and Austria did the CELIM randomised trial.

They examined the efficacy of adding cetuximab to neoadjuvant chemotherapy to improve tumour response and maximise rates of potentially curable surgery in patients with CLM.

A total of 109 patients were randomly assigned to treatment with cetuximab plus FOLFOX6 (oxaliplatin, fluorouracil, and folinic acid-group A) or cetuximab plus FOLFIRI (irinotecan, fluorouracil, and folinic acid-group B).

Using CT or MRI, the tumour response and suitability for surgery were evaluated every 4 cycles or 8 weeks. After assessment, patients with resectable (suitable for surgery) disease were offered liver surgery.

The authors also did a blinded surgical review of MRI and CT scans in order to give an objective assessment of how suitability for surgery varied during treatment.

Results indicated that treatment with cetuximab resulted in high tumour response rates. There was a significant increase of 28 percent in the proportion of tumours that were apt for surgery compared with at the start of the study.

Partial or complete tumour response was apparent in 68 percent of patients in group A and 57 percent of patients in group B.

Tumour response was superior in patients with KRAS wild-type tumours (70 percent) compared with patients with KRAS tumour mutations (41 percent).

Those results are consistent with those of previous studies which have shown that this mutation confers resistance to cetuximab.

In general, surgery was achieved in 36 of 106 patients (34 percent). Significantly, the blinded review established that treatment with cetuximab considerably increased the proportion of tumours that were suitable for surgery.

There was 60 percent (41 of 68 patients) of tumours judged to be resectable after treatment compared with 32 percent (22 of 68 patients) at the start of the study.

The treatment was generally well tolerated. Grade 3 toxicity occurred in 72 percent of patients.

The most common toxicities were skin reactions and neutropenia which is an abnormally low number of white blood cells.

The authors write in conclusion: “Our data suggest that treatment with cetuximab and chemotherapy results in high confirmed tumour response rates…leading to¦increased resectability¦In the light of recent studies in metastatic colorectal cancer the value of further treatment intensification will be investigated.”



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