By Ed Susman
SAN FRANCISCO -- January 19, 2009 -- The addition of cetuximab to standard treatment for colorectal cancer liver metastases allows patients to undergo surgery, according to research presented here at the American Society of Clinical Oncology's 6th Gastrointestinal Cancers Symposium (ASCO-GI), cosponsored by the American Gastrointestinal Association Foundation, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
About 34% of patients initially diagnosed as having unresectable metastases to the liver were able to undergo surgery and achieve an R0 dissection when cetuximab was added to their chemotherapy regimens, according to researcher Gunnar Folprecht, MD, Medical Oncology Outpatient Unit, University Hospital "Carl Gustav Carus," Medical Department I, Dresden, Germany.
Standard treatment in these patients consisted of oxaliplatin 100 mg/m2, 5-fluorouracil in a 400 mg/m2 bolus followed by a 2,400 mg/m2 infusion, and folinic acid 400 mg/m2 (FOLFOX6) or a similar regimen that replaced oxaliplatin with irinotecan (FOLFIRI).
The researchers enrolled patients with 5 or more metastases of the liver that were not considered to be candidates for surgery. The patients in the study were eligible if the metastases were found in the liver alone.
Of a total of 111 patients, Dr. Folprecht and colleagues randomised 56 patients to the FOLFOX6 regimen and another 55 patients to FOLFIRI.
Dr. Folprecht reported on the study results in an oral presentation on January 17.
After 8 cycles of treatment, patients were evaluated again for tumour resectability. If doctors agreed that the metastases could be surgically excised, the patient went to surgery and then received another 6 cycles of chemotherapy. If the evaluation determined that surgery was not recommended, the patient underwent another 4 treatment cycles before being re-evaluated.
Patients in the study had an average age of 63.3 years and 64% of the group were men. More than 75% were positive for epidermal growth factor receptor expression -- which is inhibited by cetuximab. About 45% of the patients had more than 5 liver metastases, and the other 55% had technical problems that made them initially nonresectable. About 70% of the patient's had tumours that expressed K-Ras wild-type status.
Preoperative toxicity was similar in both arms, but treatment with FOLFOX6 resulted in a higher risk of thrombopenia, nausea, and neuropathy than FOLFIRI, whereas the rate of infection and alopecia was higher with FOLFIRI than with FOLFOX6.
Dr. Folprecht said that 81% of FOLFOX6 patients responded to treatment, as did 66% of FOLFIRI patients and 76% of K-Ras wild-type tumours. The differences did not reach statistical significance.
About 38% of FOLFOX6 patients went on to receive R0 resections compared with 30% of FOLFIRI patients. About 49% of FOLFOX6 patients had R0/R1 resections compared with 43% of FOLFIRI patients. These differences also were not significant.
Of the 55% of patients for whom initial resection was technically not feasible, 28% went on to achieve resection, Dr. Folprecht said. In addition, 40% of the 48 patients, deemed not to be candidates for resection due to having 5 or more lesions, also went on to have surgery after chemotherapy. There were 2 postoperative deaths in the series.
Dr. Folprecht said the perioperative morbidity and mortality appeared to be comparable to historical experience.
Funding for this research was provided by Merck KGaA, Pfizer, and sanofi-aventis.
[Presentation title: Cetuximab Plus FOLFOX6 or Cetuximab Plus FOLFIRI as Neoadjuvant Treatment of Nonresectable Colorectal Liver Metastases: A Randomized Multicenter Study (CELIM-Study). Abstract 296]
E-Mail this DGDispatch to a colleague
