Originally published as JCO Early Release 10.1200/JCO.2005.07.740 on October 17 2005

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Oxaliplatin, Fluorouracil, and Leucovorin for Patients With Unresectable Liver-Only Metastases From Colorectal Cancer: A North Central Cancer Treatment Group Phase II Study

From the Mayo Clinic and Mayo Foundation, Rochester, MN; Toledo Community Hospital Oncology Program Community Clinical Oncology Program (CCOP), Toledo, OH; Wichita CCOP, Wichita, KS; Meritcare Hospital CCOP, Fargo, ND; Carle Cancer Center CCOP, Urbana, IL; and Geisinger Medical Center, Danville, PA.

Address reprint requests to Steven R. Alberts, MD, Mayo Clinic, 200 First St SW, Rochester, MN 55905; e-mail: alberts.steven{at}mayo.edu

	ABSTRACT

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PURPOSE: Surgical resection of liver-only metastases from colorectal cancer has undergone extensive evaluation and review. The use of neoadjuvant chemotherapy to improve the likelihood of resection in disease that is not optimally resectable has not been as well studied.

PATIENTS AND METHODS: Patients with liver-only metastases from colorectal cancer deemed not optimally resectable by a surgeon with expertise in liver surgery received fluorouracil, leucovorin, and oxaliplatin (FOLFOX4). Patients were periodically reassessed for resectability. Surgical response was classified as completely resectable (S-CR), partially resectable (S-PR), or unresectable (S-UR). Study design specified the accrual of 39 patients, with two or more S-CRs considered evidence of promising activity with respect to increasing the S-CR rate.

RESULTS: Forty-two of 44 patients were assessable for this analysis. Twenty-five patients (60%) had tumor reduction by serial imaging. Seventeen patients (40%) underwent surgery (S-CR, n = 14; S-PR, n = 1; and S-UR, n = 2) after a median of 6 months of chemotherapy. With a median postsurgical follow-up of 22 months (range, 13 to 32 months), 11 recurrences have occurred in the 15 S-CR and S-PR patients. Median survival time was 26 months.

CONCLUSION: Our data suggest that FOLFOX4 has a high response rate (complete response, partial response, or reduction) in patients with liver-only metastases from colorectal cancer, allowing for successful resection of disease in a portion of patients initially not judged to be optimally resectable. However, a high recurrence rate after surgery was observed, which, in 73% of patients, involved the liver. Further trials are indicated based on the promising results observed in this trial.

	INTRODUCTION

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The liver is the most common site of metastases in patients with colorectal cancer. As such, hepatic metastases are a major cause of morbidity and mortality in this patient population. An autopsy series of 1,541 patients who died of colorectal carcinoma showed that 44% of patients had liver metastases.¹ Metastases were restricted to the liver in 46% of these patients (20% overall). Without treatment, patients with liver metastases from colorectal cancer have a median survival time of 5 to 12 months.^2-4 Patients with limited involvement of the liver have a somewhat better survival, with 77% of these patients alive at 1 year and 14% to 23% alive at 3 years.^5,6 Resection of liver metastases can result in long-term survival in a subset of patients. A 5-year survival rate of 25% to 37% has been reported in a number of studies, with a median survival time of 24 to 42 months.⁷ However, at present, many patients with liver metastases are felt to be unresectable because of size, location, or extent of disease.

The use of neoadjuvant chemotherapy in patients with initially unresectable liver metastases has been explored in a prior study. Bismuth et al⁸ reported retrospectively on the potential for surgical resection in a group of patients receiving neoadjuvant chemotherapy with oxaliplatin, fluorouracil (FU), and leucovorin. The experiences of 330 patients with liver metastases that were determined to be unresectable by surgical evaluation were reviewed. All patients were initially treated with chemotherapy, and responses were assessed every three courses. A surgical resection was considered after each assessment. A total of 53 patients demonstrated sufficient response to chemotherapy to allow for surgical exploration. This included a group of 13 patients who were known to have associated extrahepatic disease. The surgical complication rate was 26%, with no operative mortality. The cumulative 3- and 5-year survival rates were 54% and 40%, respectively, including the patients with known extrahepatic disease.

Our study offered the opportunity, in a multicenter setting in the United States, to confirm the results of the Bismuth et al⁸ study. We performed a phase II study of oxaliplatin, FU, and leucovorin (FOLFOX4) in a group of patients with initially unresectable liver-only metastases from colorectal cancer through the North Central Cancer Treatment Group (NCCTG). Our study also offered the opportunity to evaluate the results of this approach in patients with no evidence of extrahepatic disease. The primary goal of this study was to evaluate the resectability rate of patients with not optimally resectable advanced colorectal carcinoma confined to the liver after treatment with FOLFOX4. Secondary goals included evaluating radiologic response, adverse events, and time to progression/recurrence and characterizing patterns of disease progression/recurrence.

	PATIENTS AND METHODS

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Patient Selection
Patients with liver-only metastases from colorectal cancer deemed unresectable by a surgeon experienced in liver surgery were considered potential candidates for the study. The determination that a patient was unresectable was based on the distribution of multiple lesions or the proximity of large lesions adjacent to major vasculature structures that would preclude resection with tumor-free margins. Such situations included the following: (1) metastatic disease adjacent to or apparently involving all three major hepatic veins, the portal vein bifurcation, or the retrohepatic vena cava; (2) metastatic disease adjacent to or involving the main right or main left portal vein and the main hepatic vein of the opposite lobe; and (3) metastatic disease that would require more than a right or left trisegmentectomy. The presence of six or more metastatic lesions distributed diffusely in both lobes of the liver was also considered a contraindication to surgery. Finally, patients requiring a resection that would jeopardize postoperative liver function were also considered candidates for the study.

At the time of study entry, patients were required to have imaging of the liver with computed tomography or magnetic resonance imaging, no evidence of extrahepatic disease, adequate organ function (AST 3x upper limit of normal, bilirubin within normal limits, and creatinine < 1.5x upper limit of normal), and an Eastern Cooperative Oncology Group performance status of 0 to 2. Patients were allowed to have received prior adjuvant FU and leucovorin or levamisole if administered 12 or more months before study entry. Patients were excluded from study entry if they had chronic liver disease (chronic active hepatitis or cirrhosis), had received prior therapy for metastatic disease, or had a pre-existing chronic neuropathy. Women who were pregnant or breastfeeding were also excluded from participation.

This study was approved by the Mayo Clinic (Rochester, MN) Institutional Review Board and by the institutional review boards of the individual memberships of the NCCTG that elected to participate in this study. A signed written informed consent was obtained from all patients before initiating therapy. This study was funded through the NCCTG grant from the National Cancer Institute. There was no direct industrial funding of this study. Oxaliplatin was provided free of charge to the patients.

Neoadjuvant Therapy
Patients received FOLFOX4, which consisted of biweekly oxaliplatin 85 mg/m², followed sequentially by leucovorin 200 mg/m², bolus FU 400 mg/m², and then continuous-infusion FU 600 mg/m² over 22 hours on day 1. These same doses of FU and leucovorin were repeated on day 2 without oxaliplatin. Patients were continued on treatment until best response or resectability. Study treatment was discontinued for intolerable adverse effects or progressive disease or at the patient's request. For patients undergoing resection, the protocol encouraged two to four cycles of FOLFOX4 after recovery from surgery.

Disease Evaluation
The investigator's determination of unresectability was reviewed retrospectively by one of the investigators (J.H.D.), who is an experienced hepatic surgeon. Given the multi-institutional nature of the study, it was not possible to prospectively assess each patient before enrollment. The retrospective assessment was based on the likelihood of a successful primary surgical resection as determined by a single experienced hepatic surgeon at the Mayo Clinic who examined the radiologic images.

During study participation, the clinical response rate was assessed using standard (ie, bidimensional) criteria of response. Patients were assessed radiographically for resectability at 6 and 12 weeks after starting therapy and then every other month. Patients with radiographic disappearance of all tumors were classified as having a complete response (CR). A partial response (PR) was recorded for patients having at least a 50% reduction in tumor burden. A regression (REGR) was noted in patients having a definite decrease in assessable disease. Patients were classified as having progressive disease in the case of the appearance of new lesions or an increase in tumor size by 25%. Otherwise, patients were considered as having stable disease on evaluation.

For patients who were able to undergo surgical resection, surgical response was classified as completely resectable (S-CR), partially resectable (S-PR), or unresectable (S-UR). Patients categorized as S-CR were defined as having total disappearance of all evidence of tumor at the time of operative exploration or as having had a complete resection, with or without ablation, of all hepatic metastasis(es). Patients categorized as S-PR were defined as having radiologic evidence of resectability but an incomplete resection of all hepatic metastasis(es) at the time of surgery. Patients categorized as S-UR were defined as having radiologic evidence of resectability but were found to have either hepatic metastasis(es) deemed unresectable or intraoperative evidence of extrahepatic metastases.

Definitions of Key End Points
Duration of clinical outcome was calculated from the first date of a patient's objective status of either a CR, PR, or REGR to the date of disease progression (or last tumor assessment). Time to disease progression was calculated from the date of registration to the date of disease progression/recurrence (last tumor assessment). Time to recurrence was calculated from the date of surgery for S-CR and S-PR patients to the date of disease recurrence or last tumor assessment. Time to death was calculated from the date of registration to the date of death (or last contact). Additionally, patients who died without disease progression or recurrence were classified as having no progression or recurrence at their last tumor assessment unless there was documentation otherwise.

Statistical Considerations
The primary end point of this trial was the S-CR rate. All eligible patients who initiated protocol-specified chemotherapy were considered assessable for the primary end point. The S-CR rate was calculated as the number of patients achieving an S-CR divided by the total number of assessable patients. A two-stage phase II study design was used to test whether there was sufficient evidence to determine that the S-CR rate was at least 10% (ie, clinically promising) versus, at most, 1% (ie, clinically inactive). One S-CR in the initial 28 assessable patients warranted the expansion of enrollment to 39 patients. Two S-CRs in all 39 assessable patients was considered sufficient evidence of promising activity with respect to increasing the S-CR rate. This study design has 90% power at the 0.05 level of significance to detect an S-CR rate of at least 10%. CIs are calculated using the method of Duffy and Santner,⁹ and any patient enrolled after the 39th patient is included in the second stage of accrual for this calculation.

Summary statistics and frequency tables were used to summarize baseline patient characteristics and adverse event rates. Hematologic adverse events were collected as a minimum value (ie, nadir) per course of treatment and have been converted to a common grading scale (National Cancer Institute Common Toxicity Criteria version 2.0). All attributions collected for adverse events are reported unless otherwise noted. The Kaplan-Meier method was used to estimate the distributions of duration of response, time to progression (recurrence), and time to death.¹⁰ All analyses were conducted using SAS version 8.0 (SAS Institute, Cary, NC). Two-sided P values are reported, and P < .05 is considered statistically significant.

	RESULTS

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Patient Characteristics
A total of 44 patients were enrolled between April 1999 and August 2001 from 13 NCCTG membership institutions. Two patients were declared ineligible because of the presence of extrahepatic disease. Patient characteristics at study entry and for eligible patients are listed in Table 1. A majority of patients presented with disease considered unresectable because of more than six discreet lesions (45%) or because of a combination of extent of disease, location, and size (36%). Most patients had not received prior chemotherapy or radiotherapy.

View larger version (12K): [in this window] [in a new window]   Fig 1. Patient outcome after initiation of protocol-directed therapy.

View larger version (7K): [in this window] [in a new window]   Fig 2. (A) Time to disease progression. (B) Time to disease recurrence in patients undergoing surgical resection.

Postoperative Treatment Administration and Adverse Events
Ten patients were administered postoperative FOLFOX4 within a median of 5 weeks (range, 4 to 8 weeks), receiving a median of four courses (range, two to five courses), as per protocol recommendations. Adverse event data were available for all 10 patients, and the adverse events included the following grade 3 events: neutropenia (n = 1), leukopenia (n = 3), and dyspepsia (n = 1).

Overall Survival
All patients were considered assessable for survival. With a median follow-up time of 36 months (range, 29 to 36 months), 31 patients (74%) have died. The estimated median overall survival time is 26 months for all patients (95% CI, 19 to 34 months; Table 4; Fig 3). It is not possible to estimate the median overall survival time for patients undergoing resection of their liver metastases (S-CR and S-PR) because 67% of patients were alive at 3 years (95% CI, 47% to 95%).

View larger version (9K): [in this window] [in a new window]   Fig 3. Overall survival (n = 42).

	DISCUSSION

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The use of neoadjuvant chemotherapy, initially reported by Bismuth et al,⁸ has recently been updated by Adam et al.¹⁶ In a series of 701 patients receiving oxaliplatin, chronomodulated FU, and leucovorin on a 3-week treatment cycle, 95 patients (13.6%) achieved a response after neoadjuvant therapy that was sufficient to permit curative resection. At the time of publication of the study, of 87 patients who underwent resection after neoadjuvant therapy, 34 patients (39%) were alive and 19 (22%) had no evidence of disease after 5-years of follow-up. Although this study showed promising results, its applicability is limited because of the inclusion of patients with extrahepatic metastases, because patients were treated at a single institution, and because of the use of chronomodulated therapy.

In our trial, we observed a clinical response rate of 60%, which is consistent with other studies assessing the activity of FOLFOX4 as first-line therapy for liver-limited metastatic colorectal cancer.¹⁷ The high clinical response rate translated into allowing 17 of the patients (40%) to proceed to surgical exploration, and 14 of the 17 patients underwent complete resection of their residual cancer. Although there was a high recurrence rate (71%) for patients who underwent complete resection, the median time to recurrence was 19 months (95% CI, 13 to 32 months), which was much longer than what would be expected with chemotherapy alone. In addition, the 3-year survival rate for this group of patients was 71%. As such, it seems that an aggressive surgical approach to the treatment of patients with initially unresectable liver metastases who become resectable after FOLFOX4 is reasonable. The role of postoperative chemotherapy remains uncertain. In our trial, 10 of 17 patients who underwent surgery received additional protocol-directed therapy postoperatively. Given the potential importance of the duration of therapy, our new study will mandate that patients receive a total of 10 to 12 cycles of modified FOLFOX6 (including both preoperative and postoperative therapy), as tolerated, to try to better address this concern.

It is recognized that resectability of liver metastases varies between surgeons, in part because of the experience of the surgeon. In our study, we used a definition of unresectability in an attempt to standardize this patient population. Independent surgical review by a single hepatic surgeon found that four of the patients (10%) who had been declared unresectable by their surgeon had potentially resectable disease at the time of registration. In three of the four patients, resection of the metastases would have required an extended right hepatectomy. However, it is also recognized that preoperative evaluations may not accurately predict resectability at the time of surgery. Two important points can be drawn from this information. First, designation of unresectability both inside and outside the operating room is surgeon dependent. Second, a response to the chemotherapy regimen used in this study may increase the potential for resectability regardless of the initial designation. Because of the difficulty of precisely defining unresectable, the term not optimally resectable may better describe patients in whom surgical resection is felt likely to be incomplete or impossible but in whom shrinkage of the tumor would allow resection.

For patients with liver metastases that are marginally resectable, the results of this study and the results reported by others would suggest that neoadjuvant chemotherapy enhances the likelihood of resection. The response to chemotherapy also seems to be important in predicting long-term outcome. In a retrospective study of 124 patients receiving neoadjuvant systemic chemotherapy, the 3-year survival rate after surgery was 58% for patients achieving downstaging of their metastases and 45% for patients with stable disease. None of the 28 patients with progressive disease were alive at 3 years despite surgical resection. This result indicates that control of tumor growth with neoadjuvant therapy is critical to achieving a prolonged remission.¹⁸

When patients experienced recurrence of their cancer, it most commonly occurred in the liver. This would suggest that more effective hepatic-directed therapy or more effective systemic therapy, with hepatic activity, is needed. The use of hepatic artery infusion of floxuridine has been shown to be of benefit for patients undergoing initial resection of their liver metastases. To date, no studies have been reported that specifically evaluate the benefit of adding hepatic artery infusion of floxuridine after neoadjuvant therapy for initially unresectable liver metastases compared with systemic therapy alone. The use of novel agents may also provide additional benefit. The NCCTG is currently conducting a study of FOLFOX6 and cetuximab as a potential way of enhancing the promising findings noted in this study.

	Authors' Disclosures of Potential Conflicts of Interest

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Althoguh all authors completed the disclosure declaration, the following authors or their immediate family members have indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Authors Employment Leadership Consultant Stock Honoraria Research Funds Testimony Other Steven R. Alberts Sanofi (A); Pfizer (A) Sanofi (A) Richard M. Goldberg Sanofi Synthelabo (B) Sanofi Synthelabo (B) Sanofi Synthelabo (C) Sanofi Synthelabo (N/R) Daniel J. Sargent Sanofi (A) Sanofi (A)

Dollar Amount Codes (A) <$10,000 (B) $10,000-99,999 (C) $100,000 (N/R) Not Required

	NOTES

 
Supported in part by Public Health Service Grant Nos. CA-25224, CA-37404, CA-35269, CA-60276, and CA-37417.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

	REFERENCES

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1. Weiss L, Grundmann E, Torhorst J, et al: Haematogenous metastatic patterns in colonic carcinoma: An analysis of 1541 necropsies. J Pathol 150:195-203, 1986[CrossRef][Medline]

2. Finan PJ, Marshall RJ, Cooper EH, et al: Factors affecting survival in patients presenting with synchronous hepatic metastases from colorectal cancer: A clinical and computer analysis. Br J Surg 72:373-377, 1985[Medline]

3. Goslin R, Steele G Jr, Zamcheck N, et al: Factors influencing survival in patients with hepatic metastases from adenocarcinoma of the colon or rectum. Dis Colon Rectum 25:749-754, 1982[Medline]

4. Bengtsson G, Carlsson G, Hafstrom L, et al: Natural history of patients with untreated liver metastases from colorectal cancer. Am J Surg 141:586-589, 1981[CrossRef][Medline]

5. Wagner JS, Adson MA, Van Heerden JA, et al: The natural history of hepatic metastases from colorectal cancer: A comparison with resective treatment. Ann Surg 199:502-508, 1984[Medline]

6. Wood CB, Gillis CR, Blumgart LH: A retrospective study of the natural history of patients with liver metastases from colorectal cancer. Clin Oncol 2:285-288, 1976[Medline]

7. Fong Y: Surgical therapy of hepatic colorectal metastasis. CA Cancer J Clin 49:231-255, 1999[Abstract]

8. Bismuth H, Adam R, Levi F, et al: Resection of nonresectable liver metastases from colorectal cancer after neoadjuvant chemotherapy. Ann Surg 224:509-520, 1996[CrossRef][Medline]

9. Duffy DE, Santner TJ: Confidence intervals for a binomial parameter based on multistage tests. Biometrics 43:81-93, 1987[CrossRef]

10. Kaplan EL, Meier P: Nonparameteric estimation for incomplete observations. J Am Stat Assoc 53:457-481, 1958[CrossRef]

11. Woodington G, Waugh J: Results of resection of metastatic tumors of the liver. Am J Surg 105:24-29, 1963[CrossRef][Medline]

12. Adson MA, van Heerden JA, Adson MH, et al: Resection of hepatic metastases from colorectal cancer. Arch Surg 119:647-651, 1984[Abstract/Free Full Text]

13. Hughes KS, Rosenstein RB, Songhorabodi S, et al: Resection of the liver for colorectal carcinoma metastases: A multi-institutional study of long-term survivors. Dis Colon Rectum 31:1-4, 1988[Medline]

14. Fong Y, Fortner J, Sun RL, et al: Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: Analysis of 1001 consecutive cases. Ann Surg 230:309-318, 1999[CrossRef][Medline]

15. Belli G, D'Agostino A, Ciciliano F, et al: Liver resection for hepatic metastases: 15 years of experience. J Hepatobiliary Pancreat Surg 9:607-613, 2002[CrossRef][Medline]

16. Adam R, Avisar E, Ariche A, et al: Five-year survival following hepatic resection after neoadjuvant therapy for nonresectable colorectal. Ann Surg Oncol 8:347-353, 2001[Medline]

17. de Gramont A, Figer A, Seymour M, et al: Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 18:2938-2947, 2000[Abstract/Free Full Text]

18. Adam R, Pascal G, Castaing D, et al: Liver resection for multiple colorectal metastases: Influence of preoperative chemotherapy. Proc Am Soc Clin Oncol 22:296, 2003 (abstr 1188)

Submitted November 30, 2004; accepted May 9, 2005.

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