Chemotherapy Permits Resection of Metastatic Colorectal Cancer: Experience from Intergroup N9741
Abstract & Commentary
Stuart M. Lichtman, MD, FACP, Associate Attending Memorial Sloan-Kittering Cancer Center, Commack, New York, is Associate Editor for Clinical Oncology Alert
Synopsis: Resection of metastatic disease after chemotherapy is possible in a small but important subset of patients with MCRC, particularly after receiving an oxaliplatin-based chemotherapy regimen, with encouraging OS and TTP observed in these highly selected patients.
Source: Delaunoit T, et al. Ann Oncol. 2005;16:425-429.
Colorectal cancer is the second leading cause of cancer death worldwide. Fifteen to 25% of patients will present with metastatic disease. Approximately, half of them will develop liver metastases at some point during the course of the disease. Patients with untreated metastatic disease have a median survival of less than 10 months and a 5-year survival of less than 5%. When metastases can be surgically resected, longer median overall survival of approximately 3 years have been reported.1 The recently completed randomized trial, protocol N9741, compared 3 different combinations of 5FU/LV, irinotecan, and oxaliplatin (IFL or Saltz regimen, FOLFOX4 or de Gramont regimen, and IROX or Wasserman regimen) in previously untreated metastatic colorectal cancer.2 It established FOLFOX4 as the standard of care due to improved time to progression and overall survival. The aim of this publication was to identify and describe patients treated in Intergroup Study N9741 with initially inoperable metastatic colorectal cancer who obtained sufficient chemotherapeutic benefit to allow removal of their metastatic disease.
Patients were required to have known locally advanced, locally recurrent, or metastatic colorectal adenocarcinoma not curable by surgery or amenable to radiation therapy with curative intent. The protocol did not include specific criteria for resection of metastatic disease.
Comment by Stuart M. Lichtman, MD
Seven hundred ninety-five patients were enrolled in the trial. The response rate for oxaliplatin/5FU/LV was significantly better than for irinotecan/5FU/LV or for oxaliplatin plus irinotecan. The response rates for irinotecan/5FU/LV and oxaliplatin plus irinotecan did not differ. A total of 450 records were reviewed. Twenty-six patients (3.3%) underwent attempted post-chemotherapeutic resection of their metastatic disease. Two patients were found to have peritoneal involvement at surgery, thus a total of 24 patients are considered as operated on with a curative intent. Surgical procedures included partial hepatectomy in 16 patients, radiofrequency ablation at open laparotomy in 6, and lobectomy for lung involvement in 2. The majority of patients had liver metastases. The median number of metastases in the entire cohort was 2 (range, 1-4). Twenty-two out of 24 patients who underwent curative resection of their metastatic disease had been treated with oxaliplatin-based regimens. With a median follow-up of 34 months, 14 (58%) of the resection patients are alive, and seven (29%) remain disease free, all of whom were treated with hepatectomy. Median time to tumor progression (TTP) in the 24 patients was 18.4 months. Median overall survival was 42.4 months. When compared with patients achieving CR without resection (n = 42), similar results were observed, (median TTP, 14.8 months; median overall survival [OS], 39.2 months). Patients experiencing partial recovery without subsequent metastatic resection achieved a median TTP of 10 months and a median OS of 21 months. Five patients treated by hepatectomy received adjuvant treatment, including hepatic arterial infusion of floxuridine (4) and/or systemic infusion of 5-FU/LV (2). After a median 32 months of follow-up, all but one of these patients (80%) remain disease-free.
Surgery remains the only potentially curative treatment for metastatic disease. This trial resulted in a 3.3% metastatic disease-resection rate. The majority of resected patients had been assigned to one of the oxaliplatin-based regimens, confirming the role of oxaliplatin as an important agent in making metastatic lesions surgically resectable. Tournigand et al found similar results in their trial, with a significant difference between patients treated with FOLFOX6 and FOLFIRI (22% vs 9%).3 This current study also showed that 71% of patients develop disease recurrence after curative surgery, with 94% of these recurrences in the surgically treated organ. There is some evidence that intrahepatic chemotherapy after resection may improve survival.4 This study should encourage aggressive approaches to the treatment of colorectal cancer metastases. Unfortunately the benefit of this approach will only be appropriate for a small number of patients.
References
- Fong Y, et al. J Clin Oncol. 1997;15:938-946.
- Goldberg RM, et al. J Clin Oncol. 2004;22:23-30.
- Tournigand C, et al. J Clin Oncol. 2004;22:229-237.
- Kemeny MM, et al. J Clin Oncol. 2002;20:1499-1505.
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