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Multiple treatment lines and prognosis in metastatic colorectal cancer patients

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Abstract

The proportion of patients with metastatic colorectal cancer (mCRC) receiving second or further lines of treatment has not been widely studied. To shed light on this issue, we retrospectively analysed the treatments administered for metastatic disease, and investigated prognostic factors after a diagnosis of metastases, in a consecutive cohort of mCRC patients. Three hundred forty-six mCRC patients were enrolled: 173 were stage II or III (metachronous group), and 173 stage IV (synchronous group) at diagnosis. Survival was calculated between the date of metastatic disease and the date of death or last follow-up. Patients with synchronous lesions more frequently had multiple disease sites, peritoneal carcinomatosis and massive liver deposits, whereas significantly more patients with metachronous lesions developed lung metastases as the sole disease site. 97.4% patients received at least one, 62.4% two, 41.9% three and 23.7% four treatment lines. Patients with metachronous metastases more frequently underwent surgery of metastases in first-line treatment (48.5 versus 24.8%), and more of them were progression-free at the time of the analysis (44 versus 34.9%). At univariate analysis, age > 70 years, multiple disease sites and peritoneal carcinomatosis were associated with significantly decreased survival, whereas surgery of metastases and isolated lung metastases predicted better survival. At multivariate analysis, only peritoneal carcinomatosis and surgery of metastases independently affected survival. The percentage of patients who received an active treatment decreased going from first- to fourth-line treatment. However, the proportion of patients who received efficacious treatment in advanced line remained high. Surgery of metastases was the most important prognostic factors.

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References

  1. Torre, L. A., Bray, F., Siegel, R. L., Ferlay, J., Lortet-Tieulent, J., & Jemal, A. (2015). Global cancer statistics 2012. CA: a Cancer Journal for Clinicians, 65(2), 87–108.

    Google Scholar 

  2. Coviello, V., Buzzoni, C., Fusco, M., et al for the AIRTUM Working Group.(2017). Survival of cancer patients in Italy. Epidemiol Prev, 41(2 Suppl 1), 1–244.

  3. Gao, P., Song, Y. X., Wang, Z. N., Xu, Y. Y., Tong, L. L., Sun, J. X., Yu, M., & Xu, H. M. (2013). Is the prediction of prognosis not improved by the seventh edition of the TNM classification for colorectal cancer? Analysis of the surveillance, epidemiology, and end results (SEER) database. BMC Cancer, 13, 123.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Siegel, R., Desantis, C., & Jemal, A. (2014). Colorectal cancer statistics 2014. CA Cancer J Clin, 64(2), 104–117.

    Article  PubMed  Google Scholar 

  5. Hewitson, P., Glasziou, P., Watson, E., Towler, B., & Irwig, L. (2008). Cochrane systematic review of colorectal cancer screening using the fecal occult blood test (Hemoccult): an update. The American Journal of Gastroenterology, 103(6), 1541–1549.

    Article  PubMed  Google Scholar 

  6. Elmunzer, B. J., Hayward, R. A., Schoenfeld, P. S., et al. (2012). Effect of flexible sigmoidoscopy-based screening on incidence and mortality of colorectal cancer: a systematic review and meta-analysis of randomized controlled trials. Plos Medicine, 9(12), e1001352.

    Article  PubMed  PubMed Central  Google Scholar 

  7. André, T., Boni, C., Navarro, M., Tabernero, J., Hickish, T., Topham, C., Bonetti, A., Clingan, P., Bridgewater, J., Rivera, F., & de Gramont, A. (2009). Improved overall survival with Oxaliplatin, Fluorouracil and Leucovorin as adjuvant treatment for stage II or III colon cancer in the MOSAIC trial. Journal of Clinical Oncology, 27(19), 3109–3116.

    Article  CAS  PubMed  Google Scholar 

  8. Figueredo, A., Coombes, M. E., & Mukherjee, S. (2008). Adjuvant therapy for completely resected stage II colon Cancer (review). Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.CD005390.pub2.

  9. Kapiteijn E., Marijnen C.A.M., Nagtegaal I.D. et al for the Dutch Colorectal Cancer Group.(2001). Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. The New England Journal of Medicine, 345(9), 638–646.

  10. Sauer, R., Becker, H., Hohenberger, W., Rödel, C., Wittekind, C., Fietkau, R., Martus, P., Tschmelitsch, J., Hager, E., Hess, C. F., Karstens, J. H., Liersch, T., Schmidberger, H., Raab, R., & German Rectal Cancer Study Group. (2004). Preoperative versus postoperative chemoradiotherapy for rectal cancer. The New England Journal of Medicine, 351(17), 1731–1740.

    Article  CAS  PubMed  Google Scholar 

  11. Hurwitz, H., Fehrenbacher, L., Novotny, W., Cartwright, T., Hainsworth, J., Heim, W., Berlin, J., Baron, A., Griffing, S., Holmgren, E., Ferrara, N., Fyfe, G., Rogers, B., Ross, R., & Kabbinavar, F. (2004). Bevacizumab plus irinotecan, fluorouracil, and leucovorinfor metastatic colorectal cancer. The New England Journal of Medicine, 350(23), 2335–2342.

    Article  CAS  PubMed  Google Scholar 

  12. Saltz, L. B., Clarke, S., Diaz-Rubio, E., et al. (2008). Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. Journal of Clinical Oncology, 26(12), 2013–2019.

    Article  CAS  PubMed  Google Scholar 

  13. Van Cutsem, E., Köhne, C. H., Láng, I., et al. (2011). Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. Journal of Clinical Oncology, 29(15), 2011–2019.

    Article  CAS  PubMed  Google Scholar 

  14. Douillard, J., Oliner, K. S., Siena, S., et al. (2013). Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. The New England Journal of Medicine, 369(11), 1023–1034.

    Article  CAS  PubMed  Google Scholar 

  15. Van Cutsem, E., Tabernero, J., Lakomy, R., et al. (2012). Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with oxaliplatin-based regimen. Journal of Clinical Oncology, 30(28), 2499–2506.

    Google Scholar 

  16. Grothey, A., Van Cutsem, E., Sobrero, A., et al. (2013). Regorafenib monotherapy for previous treated metastatic colorectal cancer (CORRECT): an international, multicenter, randomized, placebo-controlled, phase 3 trial. Lancet, 381(9863), 303–312.

    Article  CAS  PubMed  Google Scholar 

  17. \Mayer, R. J., Van Cutsem, E., Falcone, F., et al. (2015). Randomized trial of TAS-102 for refractory metastatic colorectal cancer. The New England Journal of Medicine, 372(20), 1909–1919.

    Article  PubMed  Google Scholar 

  18. Tomlinson, J. S., Jarnagin, W. R., De Matteo, R. P., et al. (2007). Actual 10-year survival after resection of colorectal liver metastases defines cure. Journal of Clinical Oncology, 25(29), 4575–4580.

    Article  PubMed  Google Scholar 

  19. Adam, R., Wicherts, D. A., de Haas, R. J., Ciacio, O., Lévi, F., Paule, B., Ducreux, M., Azoulay, D., Bismuth, H., & Castaing, D. (2009). Patients with initially unresectable colorectal liver metastases: is there a possibility of cure? Journal of Clinical Oncology, 27(11), 1829–1835.

    Article  PubMed  Google Scholar 

  20. Grothey, A., Sargent, D., Goldberg, R. M., & Schmoll, H. J. (2004). Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment. Journal of Clinical Oncology, 22(7), 1209–1214.

    Article  CAS  PubMed  Google Scholar 

  21. Tournigand, C., André, T., Achille, E., Lledo, G., Flesh, M., Mery-Mignard, D., Quinaux, E., Couteau, C., Buyse, M., Ganem, G., Landi, B., Colin, P., Louvet, C., & de Gramont, A. (2004). FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. Journal of Clinical Oncology, 22(2), 229–237.

    Article  CAS  PubMed  Google Scholar 

  22. Seal, B., Chaster, B., Kulakodlu, M., et al. (2015). Difference in survival for patients with metastatic colorectal cancer by lines of treatment received and stage at original diagnosis. International Journal of Clinical Practice, 69(2), 251–258.

    Article  CAS  PubMed  Google Scholar 

  23. Abrams, T., Meyer, G., Schrag, D., et al. (2014). Chemotherapy usage patterns in a US-wide cohort of patients with metastatic colorectal cancer. J Natl Cancer Inst, 106(2), djt371.

    Article  CAS  PubMed  Google Scholar 

  24. Hess, G. P., Wang, P. F., Quach, D., Barber, B., & Zhao, Z. (2010). Systemic therapy for metastatic colorectal cancer: patterns of chemotherapy and biologic therapy use in US medical oncology practice. Journal of Oncology Practice/ American Society of Clinical Oncology, 6(6), 301–307.

    Article  Google Scholar 

  25. McLean, J., Rho, Y. S., Kuruba, G., Mamo, A., Gilabert, M., Kavan, T., Panasci, L., Melnychuk, D., Batist, G., & Kavan, P. (2016). Clinical practice patterns in chemotherapeutic treatment regimens for metastatic colorectal cancer. Clinical Colorectal Cancer, 15(2), 135–140.

    Article  PubMed  Google Scholar 

  26. Tampellini, M., Di Maio, M., Baratelli, C., et al. (2017). Treatment of patients with metastatic colorectal cancer in a real-world scenario: probability of receiving second and further lines of therapy and description of clinical benefit. Clinical Colorectal Cancer, 16(4), 372–376.

    Article  PubMed  Google Scholar 

  27. Schwartzberg, L. S., Rivera, F., Karthaus, M., et al. (2017). A randomized, multicenter phase II study of Panitumumab plus modified fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, Unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. Journal of Clinical Oncology, 32(21), 2240–2247.

    Article  CAS  Google Scholar 

  28. Modest, D. P., Stintzing, S., Fischer von Weikersthal, L., et al. (2015). Impact of subsequent therapies on outcome of the FIRE-3/AIO KRK0306 trial: first-line therapy with FOLFIRI plus cetuximab or bevacizumab in patients with KRAS wild-type tumors in metastatic colorectal cancer. Journal of Clinical Oncology, 33(32), 718–723.

    Article  CAS  Google Scholar 

  29. Cremolini, C., Loupakis, F., Antoniotti, C., Lupi, C., Sensi, E., Lonardi, S., Mezi, S., Tomasello, G., Ronzoni, M., Zaniboni, A., Tonini, G., Carlomagno, C., Allegrini, G., Chiara, S., D’Amico, M., Granetto, C., Cazzaniga, M., Boni, L., Fontanini, G., & Falcone, A. (2015). FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. The Lancet Oncology, 16(13), 1306–1315.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Jean Ann Gilder (Scientific Communication srl., Naples, Italy) for text editing and linguistic revision.

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Authors and Affiliations

  1. Department of Clinical Medicine and Surgery, University Federico II, Via Sergio Pansini, 5, 80131, Naples, Italy

    Chiara Carlomagno, Mario Rosanova, Stefano De Falco, Laura Attademo, Giovanni Fiore & Sabino De Placido

  2. Department of Abdominal Oncology, National Cancer Institute “G. Pascale”, Via Mariano Semmola, 53, 80131, Naples, Italy

    Alfonso De Stefano

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  1. Chiara Carlomagno
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  2. Alfonso De Stefano
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  3. Mario Rosanova
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Correspondence to Chiara Carlomagno.

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Carlomagno, C., De Stefano, A., Rosanova, M. et al. Multiple treatment lines and prognosis in metastatic colorectal cancer patients. Cancer Metastasis Rev 38, 307–313 (2019). https://doi.org/10.1007/s10555-018-9748-7

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