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      Major Surgery in Patients with Metastatic Colorectal Cancer in Western Europe

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          Abstract

          Purpose

          Given the potential interference between treatment for metastatic colorectal cancer (mCRC) and surgical procedures, we sought to determine the prevalence of major surgery following mCRC diagnosis in clinical practice.

          Methods

          This cohort study used physician-surveyed data from the LifeLink™ Oncology Analyzer database for mCRC patients in five European countries (France, Germany, Italy, Spain, and the United Kingdom [UK]). All patients aged ≥21 years at mCRC diagnosis and with data collected during 2009 were included. Major surgical procedures were examined descriptively by the purpose and location of surgery.

          Results

          The study sample included 3,249 mCRC patients; 515, 862, 656, 649, and 567 were from France, Germany, Italy, Spain, and the UK, respectively. Following mCRC diagnosis, at least one major surgical procedure for any purpose was seen in 30.5% (UK), 35.2% (Germany), 35.6% (Spain), 36.3% (France), and 38.4% (Italy) of patients, with a mean of 1.3 (UK) to 1.6 (France) procedures. The rate of major surgery for curative purposes was the highest in Italy (13.4%), followed by France (12.8%), Spain (10.3%), and Germany (9.2%); the lowest was in the UK (7.2%). Major surgery performed on the primary tumor (12.4–27.1% of patients, depending on the country) and metastasis (6.4–14.6%) made up the majority of all surgical procedures.

          Conclusions

          Major surgery is highly prevalent following mCRC diagnosis, suggesting an important role in meeting the goals of mCRC treatment. The role of pharmacological treatment options and their potential to interfere with both surgery use and surgical outcomes should be considered when evaluating mCRC treatment strategies.

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          Most cited references11

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          Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study.

          To evaluate the efficacy and safety of bevacizumab when added to first-line oxaliplatin-based chemotherapy (either capecitabine plus oxaliplatin [XELOX] or fluorouracil/folinic acid plus oxaliplatin [FOLFOX-4]) in patients with metastatic colorectal cancer (MCRC). Patients with MCRC were randomly assigned, in a 2 x 2 factorial design, to XELOX versus FOLFOX-4, and then to bevacizumab versus placebo. The primary end point was progression-free survival (PFS). A total of 1,401 patients were randomly assigned in this 2 x 2 analysis. Median progression-free survival (PFS) was 9.4 months in the bevacizumab group and 8.0 months in the placebo group (hazard ratio [HR], 0.83; 97.5% CI, 0.72 to 0.95; P = .0023). Median overall survival was 21.3 months in the bevacizumab group and 19.9 months in the placebo group (HR, 0.89; 97.5% CI, 0.76 to 1.03; P = .077). Response rates were similar in both arms. Analysis of treatment withdrawals showed that, despite protocol allowance of treatment continuation until disease progression, only 29% and 47% of bevacizumab and placebo recipients, respectively, were treated until progression. The toxicity profile of bevacizumab was consistent with that documented in previous trials. The addition of bevacizumab to oxaliplatin-based chemotherapy significantly improved PFS in this first-line trial in patients with MCRC. Overall survival differences did not reach statistical significance, and response rate was not improved by the addition of bevacizumab. Treatment continuation until disease progression may be necessary in order to optimize the contribution of bevacizumab to therapy.
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            Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study.

            Panitumumab, a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody that improves progression-free survival (PFS), is approved as monotherapy for patients with chemotherapy-refractory metastatic colorectal cancer (mCRC). The Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy (PRIME) was designed to evaluate the efficacy and safety of panitumumab plus infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as initial treatment for mCRC. In this multicenter, phase III trial, patients with no prior chemotherapy for mCRC, Eastern Cooperative Oncology Group performance status of 0 to 2, and available tissue for biomarker testing were randomly assigned 1:1 to receive panitumumab-FOLFOX4 versus FOLFOX4. The primary end point was PFS; overall survival (OS) was a secondary end point. Results were prospectively analyzed on an intent-to-treat basis by tumor KRAS status. KRAS results were available for 93% of the 1,183 patients randomly assigned. In the wild-type (WT) KRAS stratum, panitumumab-FOLFOX4 significantly improved PFS compared with FOLFOX4 (median PFS, 9.6 v 8.0 months, respectively; hazard ratio [HR], 0.80; 95% CI, 0.66 to 0.97; P = .02). A nonsignificant increase in OS was also observed for panitumumab-FOLFOX4 versus FOLFOX4 (median OS, 23.9 v 19.7 months, respectively; HR, 0.83; 95% CI, 0.67 to 1.02; P = .072). In the mutant KRAS stratum, PFS was significantly reduced in the panitumumab-FOLFOX4 arm versus the FOLFOX4 arm (HR, 1.29; 95% CI, 1.04 to 1.62; P = .02), and median OS was 15.5 months versus 19.3 months, respectively (HR, 1.24; 95% CI, 0.98 to 1.57; P = .068). Adverse event rates were generally comparable across arms with the exception of toxicities known to be associated with anti-EGFR therapy. This study demonstrated that panitumumab-FOLFOX4 was well tolerated and significantly improved PFS in patients with WT KRAS tumors and underscores the importance of KRAS testing for patients with mCRC.
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              Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer.

              Panitumumab is a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody that improves progression-free survival (PFS) in chemotherapy-refractory metastatic colorectal cancer (mCRC). This trial evaluated the efficacy and safety of panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone after failure of initial treatment for mCRC by tumor KRAS status. Patients with mCRC, one prior chemotherapy regimen for mCRC, Eastern Cooperative Oncology Group performance status 0 to 2, and available tumor tissue for biomarker testing were randomly assigned 1:1 to panitumumab 6.0 mg/kg plus FOLFIRI versus FOLFIRI every 2 weeks. The coprimary end points of PFS and overall survival (OS) were independently tested and prospectively analyzed by KRAS status. From June 2006 to March 2008, 1,186 patients were randomly assigned 1:1 and received treatment. KRAS status was available for 91% of patients: 597 (55%) with wild-type (WT) KRAS tumors, and 486 (45%) with mutant (MT) KRAS tumors. In the WT KRAS subpopulation, when panitumumab was added to chemotherapy, a significant improvement in PFS was observed (hazard ratio [HR] = 0.73; 95% CI, 0.59 to 0.90; P = .004); median PFS was 5.9 months for panitumumab-FOLFIRI versus 3.9 months for FOLFIRI. A nonsignificant trend toward increased OS was observed; median OS was 14.5 months versus 12.5 months, respectively (HR = 0.85, 95% CI, 0.70 to 1.04; P = .12); response rate was improved to 35% versus 10% with the addition of panitumumab. In patients with MT KRAS, there was no difference in efficacy. Adverse event rates were generally comparable across arms with the exception of known toxicities associated with anti-EGFR therapy. Panitumumab plus FOLFIRI significantly improved PFS and is well-tolerated as second-line treatment in patients with WT KRAS mCRC.
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                Author and article information

                Contributors
                +1-805-4474908 , +1-805-3761816 , zhongyun@amgen.com
                Journal
                J Gastrointest Cancer
                J Gastrointest Cancer
                Journal of Gastrointestinal Cancer
                Springer US (Boston )
                1941-6628
                1941-6636
                29 November 2011
                29 November 2011
                September 2012
                : 43
                : 3
                : 456-461
                Affiliations
                [1 ]Global Health Economics, Amgen Inc, One Amgen Center Drive, Thousand Oaks, CA 91320-1799 USA
                [2 ]IMS Consulting Group, Falls Church, VA USA
                Article
                9349
                10.1007/s12029-011-9349-y
                3425743
                22125088
                ced667f6-40a0-48e5-88fc-873d635af650
                © The Author(s) 2011
                History
                Categories
                Original Research
                Custom metadata
                © Springer Science+Business Media, LLC 2012

                Oncology & Radiotherapy
                metastasis,surgery,monoclonal antibodies,colorectal cancer
                Oncology & Radiotherapy
                metastasis, surgery, monoclonal antibodies, colorectal cancer

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