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Skeletal muscle loss during anti-EGFR combined chemotherapy regimens predicts poor prognosis in patients with RAS wild metastatic colorectal cancer

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Abstract

Purpose

We aimed to assess whether anti-EGFR combined chemotherapy regimens are related with loss of skeletal muscle mass and to compare cetuximab and panitumumab therapies in the aspect of skeletal muscle area change as well as to assess whether skeletal muscle mass loss has prognostic significance in the RAS wild mCRC patients.

Materials and methods

A total of 56 patients (30 patients in cetuximab arm and 26 patients in panitumumab) who had computed tomography images were retrospectively evaluated at the diagnosis and follow up during the treatment period before progression.

Results

During treatment period 24 patients (42.8%) had muscle loss. Of these, 7 (29.2%) patients were treated at first-line and 17 (70.8%) patients were treated at second-line setting. There was no significant difference in the aspect of skeletal muscle loss among cetuximab and panitumumab combined treatment regimens. Median PFS was 9.1 (8.6–9.6) months in muscle loss group and 13.9 (7.2–20.6) months in muscle stable group (p = 0.001). Median OS was 23.4 (95% CI 15.8–31.0) months in muscle stable group and 19.1 (95% CI 17.0–21.3) months in muscle loss group (p = 0.57) at first-line setting. For second-line, median OS was 21.2 (14.7–27.7) months in muscle stable group and 14.4 (6.0-22.4) months in muscle loss group (p = 0.003).

Conclusions

Decrease in skeletal muscle mass before progression on CT imaging is an independent indicator for shorter PFS value in RAS WT mCRC patients who received anti-EGFR combined chemotherapy regimens at both the first and second-line settings. Beside that shorter overall survival values also were significantly seen in patients who had muscle loss during anti-EGFR therapy in the second-line setting.

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References

  1. Noone A, Howlader N, Krapcho M et al. SEER Cancer Statistics Review, 1975-2015, based on November 2017 SEER data submission, posted to the SEER web site, April 2018. Bethesda, MD: National Cancer Institute; 2018. In. 2018.

  2. Herbst RS, Shin DM. Monoclonal antibodies to target epidermal growth factor receptor-positive tumors: a new paradigm for cancer therapy. Cancer. 2002;94:1593–611.

    Article  CAS  Google Scholar 

  3. Ottaiano A, De Stefano A, Capozzi M, et al. First Biologic Drug in the Treatment of RAS Wild-Type Metastatic Colorectal Cancer: Anti-EGFR or Bevacizumab? Results From a Meta-Analysis. Front Pharmacol. 2018;9:441.

    PubMed  Google Scholar 

  4. Van Cutsem E, Kohne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360:1408–17.

    Article  Google Scholar 

  5. Peeters M, Price TJ, Cervantes A, et al. 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. J Clin Oncol. 2010;28:4706–13.

    Article  CAS  Google Scholar 

  6. Douillard JY, Siena S, Cassidy J, et al. 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. J Clin Oncol. 2010;28:4697–705.

    Article  CAS  Google Scholar 

  7. Bokemeyer C, Bondarenko I, Makhson A, et al. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2009;27:663–71.

    Article  CAS  Google Scholar 

  8. Fukushima H, Takemura K, Suzuki H, Koga F. Impact of Sarcopenia as a Prognostic Biomarker of Bladder Cancer. 2018; 19.

  9. Argiles JM, Busquets S, Stemmler B, Lopez-Soriano FJ. Cancer cachexia: understanding the molecular basis. Nat Rev Cancer. 2014;14:754–62.

    Article  CAS  Google Scholar 

  10. Antoun S, Baracos VE, Birdsell L, et al. Low body mass index and sarcopenia associated with dose-limiting toxicity of sorafenib in patients with renal cell carcinoma. Ann Oncol. 2010;21:1594–8.

    Article  CAS  Google Scholar 

  11. Mitsiopoulos N, Baumgartner RN, Heymsfield SB, et al. Cadaver validation of skeletal muscle measurement by magnetic resonance imaging and computerized tomography. J Appl Physiol. 1985;1998(85):115–22.

    Google Scholar 

  12. Kurk SA, Peeters PHM, Dorresteijn B, et al. Impact of different palliative systemic treatments on skeletal muscle mass in metastatic colorectal cancer patients. J Cachexia Sarcopenia Muscle. 2018;9:909–19.

    Article  Google Scholar 

  13. Hecht JR, Douillard JY, Schwartzberg L, et al. Extended RAS analysis for anti-epidermal growth factor therapy in patients with metastatic colorectal cancer. Cancer Treat Rev. 2015;41:653–9.

    Article  CAS  Google Scholar 

  14. Douillard JY, Siena S, Cassidy J, et al. Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol. 2014;25:1346–55.

    Article  CAS  Google Scholar 

  15. Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15:1065–75.

    Article  CAS  Google Scholar 

  16. Ciardiello F, Lenz H-J, Kohne C-H et al. Treatment outcome according to tumor RAS mutation status in CRYSTAL study patients with metastatic colorectal cancer (mCRC) randomized to FOLFIRI with/without cetuximab. In. American Society of Clinical Oncology 2014.

  17. Price TJ, Peeters M, Kim TW, et al. Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol. 2014;15:569–79.

    Article  CAS  Google Scholar 

  18. Miyake M, Morizawa Y, Hori S, et al. Clinical impact of postoperative loss in psoas major muscle and nutrition index after radical cystectomy for patients with urothelial carcinoma of the bladder. BMC Cancer. 2017;17:237.

    Article  Google Scholar 

  19. Zargar H, Almassi N, Kovac E, et al. Change in Psoas Muscle Volume as a Predictor of Outcomes in Patients Treated with Chemotherapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer. Bladder Cancer. 2017;3:57–63.

    Article  Google Scholar 

  20. Fukushima H, Kataoka M, Nakanishi Y, et al. Posttherapeutic skeletal muscle mass recovery predicts favorable prognosis in patients with advanced urothelial carcinoma receiving first-line platinum-based chemotherapy. Urol Oncol. 2018;36(156):e159–156.e116.

    Google Scholar 

  21. Levolger S, van Vugt JL, de Bruin RW, JN IJ. Systematic review of sarcopenia in patients operated on for gastrointestinal and hepatopancreatobiliary malignancies. Br J Surg 2015; 102: 1448-1458.

    Article  CAS  Google Scholar 

  22. Kamarajah SK, Bundred J, Tan BH. Body composition assessment and sarcopenia in patients with gastric cancer: a systematic review and meta-analysis. Gastric Cancer 2018; 1-13.

  23. Fukushima H, Takemura K, Suzuki H, Koga F. Impact of Sarcopenia as a Prognostic Biomarker of Bladder Cancer. Int J Mol Sci. 2018;19:2999.

    Article  Google Scholar 

  24. Chang K-V, Chen J-D, Wu W-T, et al. Association between Loss of Skeletal Muscle Mass and Mortality and Tumor Recurrence in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. Liver cancer. 2018;7:90–103.

    Article  Google Scholar 

  25. Ozola Zalite I, Zykus R, Francisco Gonzalez M, et al. Influence of cachexia and sarcopenia on survival in pancreatic ductal adenocarcinoma: a systematic review. Pancreatology. 2015;15:19–24.

    Article  CAS  Google Scholar 

  26. Deng HY, Hou L, Zha P et al. Sarcopenia is an independent unfavorable prognostic factor of non-small cell lung cancer after surgical resection: A comprehensive systematic review and meta-analysis. Eur J Surg Oncol 2018.

  27. van Vledder MG, Levolger S, Ayez N, et al. Body composition and outcome in patients undergoing resection of colorectal liver metastases. Br J Surg. 2012;99:550–7.

    Article  Google Scholar 

  28. Miyamoto Y, Suyama K, Baba H. Recent Advances in Targeting the EGFR Signaling Pathway for the Treatment of Metastatic Colorectal Cancer. Int J Mol Sci 2017; 18.

  29. Hodson N, Philp A. The Importance of mTOR Trafficking for Human Skeletal Muscle Translational Control. Exerc Sport Sci Rev. 2019;47:46–53.

    Article  Google Scholar 

  30. Zhang Q, Duplany A, Moncollin V et al. Lack of muscle mTOR kinase activity causes early onset myopathy and compromises whole-body homeostasis. 2018.

  31. Yoon MS. mTOR as a Key Regulator in Maintaining Skeletal Muscle Mass. Front Physiol. 2017;8:788.

    Article  Google Scholar 

  32. Gyawali B, Shimokata T, Honda K, et al. Muscle wasting associated with the long-term use of mTOR inhibitors. Mol Clin Oncol. 2016;5:641–6.

    Article  CAS  Google Scholar 

  33. Blauwhoff-Buskermolen S, Versteeg KS, de van der Schueren MA et al. Loss of Muscle Mass During Chemotherapy Is Predictive for Poor Survival of Patients With Metastatic Colorectal Cancer. J Clin Oncol 2016; 34: 1339-1344.

    Article  CAS  Google Scholar 

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Correspondence to O. Köstek.

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Köstek, O., Demircan, N.C., Gökyer, A. et al. Skeletal muscle loss during anti-EGFR combined chemotherapy regimens predicts poor prognosis in patients with RAS wild metastatic colorectal cancer. Clin Transl Oncol 21, 1510–1517 (2019). https://doi.org/10.1007/s12094-019-02079-x

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  • DOI: https://doi.org/10.1007/s12094-019-02079-x

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