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Italian survey on cetuximab-based therapy of elderly patients with metastatic colorectal cancer

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Abstract

Purpose

There is no consensus on the use of cetuximab in elderly patients with metastatic colorectal cancer. To this end, a survey was carried in 17 Italian oncology centers.

Methods

The centers answered a 29-item questionnaire structured as follows: (i) demographic characteristics; (ii) medical history; (iii) assessment of RAS/BRAF mutations and DPD/UGT polymorphism before treatment; (iv) treatment schemes and side effects; (v) geriatric assessment and customization of treatment.

Results

One-third of patients are over 80 years old. The RAS/BRAF mutational status is not primarily evaluated by 17.6% of the centers, while DPD and UGT polymorphism is not evaluated by 82.4% and 76.5% of the centers. The most common therapeutic scheme is cetuximab/FOLFIRI and diarrhea is the main cause of suspension/reduction of treatment. The 70% of centers use systemic tetracyclines for skin toxicity. The 23.5% of the centers do not carry out any geriatric evaluation before the start of the therapy and those who perform it prefer the G8 (70.6%) and VES-13 (29.4%) scales.

Conclusions

Greater efforts should be made to improve the evaluation of the patient both about mutational and genetic procedures with geriatric evaluation. As for cetuximab in elderly patients, randomized studies are needed to provide guidance to physicians.

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References

  1. Tuppin P, Pestel L, Samson S, Cuerg A, Rivière S, Tala S, Denis P, Drouin J, Gissot C, Gastaldi-Ménager C, Fagot-Campagna A (2017) Poids humain et économique des cancers en France en 2014, les données du Sniiram. Bull Cancer 104:524–537

    Article  PubMed  Google Scholar 

  2. World Cancer Research Fund International. Colorectal cancer statistics. https://www.wcrf.org/int/cancer-facts-figures/data-specific-cancers/colorectal-cancer-statistics (2016) Accessed 15 July 2018

  3. Aaldriks AA, Maartense E, le Cessie S, Giltay EJ, Verlaan HA, van der Geest LG, Kloosterman-Boele WM, Peters-Dijkshoorn MT, Blansjaar BA, van Schaick HW, Nortier JW (2011) Predictive value of geriatric assessment for patients older than 70 years, treated with chemotherapy. Crit Rev Oncol Hematol 79:205–212

    Article  CAS  PubMed  Google Scholar 

  4. Egenvall M, Schubert Samuelsson K, Klarin I, Lökk J, Sjövall A, Martling A, Gunnarsson U (2014) Management of colon cancer in the elderly: a population-based study. Color Dis 16:433–441

    Article  CAS  Google Scholar 

  5. Bokemeyer C, van Cutsem E, Rougier P, Ciardiello F, Heeger S, Schlichting M, Celik I, Köhne CH (2012) Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer 48:1466–1475

    Article  CAS  PubMed  Google Scholar 

  6. Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Smakal M, Canon JL, Rother M, Oliner KS, Tian Y, Xu F, Sidhu R (2014) Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol 25:1346–1355

    Article  CAS  PubMed  Google Scholar 

  7. Van Cutsem E, Köhne CH, Folprecht G, Guenther S, Beier F, Papamichael D (2016) Efficacy and safety of first-line cetuximab + FOLFIRI in older and younger patients (pts) with RAS wild-type (wt) metastatic colorectal cancer (mCRC) in the CRYSTAL study. J Clin Oncol 34(Suppl 4):647

    Article  Google Scholar 

  8. Folprecht G, Köhne CH, Bokemeyer C, Rougier P, Schlichting M, Heeger S, van Cutsem E (2010) Cetuximab and 1st-line chemotherapy in elderly and younger patients with metastatic colorectal cancer (MCRC): a pooled analysis of the CRYSTAL and OPUS studies. Ann Oncol 21(Suppl 8):94

    Google Scholar 

  9. Rosati G, Aprile G, Cardellino GG, Avallone A (2016) A review and assessment of currently available data of the EGFR antibodies in elderly patients with metastatic colorectal cancer. J Geriatr Oncol 7:134–141

    Article  PubMed  Google Scholar 

  10. Heinemann V, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, Heintges T, Lerchenmüller C, Kahl C, Seipelt G, Kullmann F, Stauch M, Scheithauer W, Hielscher J, Scholz M, Müller S, Link H, Niederle N, Rost A, Höffkes HG, Moehler M, Lindig RU, Modest DP, Rossius L, Kirchner T, Jung A, Stintzing S (2014) 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 15:1065–1075

    Article  CAS  PubMed  Google Scholar 

  11. Venook AP, Niedzwiecki D, Lenz HJ, Innocenti F, Fruth B, Meyerhardt JA, Schrag D, Greene C, O’Neil BH, Atkins JN, Berry S, Polite BN, O’Reilly EM, Goldberg RM, Hochster HS, Schilsky RL, Bertagnolli MM, El-Khoueiry AB, Watson P, Benson AB, Mulkerin DL, Mayer RJ, Blanke C (2017) Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in patients with KRAS wild-type advanced or metastatic colorectal cancer: a randomized clinical trial. JAMA 317:2392–2401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Arnold D, Lueza B, Douillard JY, Peeters M, Lenz HJ, Venook A, Heinemann V, Van Cutsem E, Pignon JP, Tabernero J, Cervantes A, Ciardiello F (2017) Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials. Ann Oncol 28:1713–1729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Holch JW, Ricard I, Stintzing S, Modest DP, Heinemann V (2017) The relevance of primary tumour location in patients with metastatic colorectal cancer: a meta-analysis of first-line clinical trials. Eur J Cancer 70:87–98

    Article  PubMed  Google Scholar 

  14. Cunningham D, Lang I, Marcuello E, Lorusso V, Ocvirk J, Shin DB, Jonker D, Osborne S, Andre N, Waterkamp D, Saunders MP (2013) AVEX study investigators. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol 14:1077–1085

    Article  CAS  PubMed  Google Scholar 

  15. Sastre J, Grávalos C, Rivera F, Massuti B, Valladares-Ayerbes M, Marcuello E, Manzano JL, Benavides M, Hidalgo M, Díaz-Rubio E, Aranda E (2012) First-line cetuximab plus capecitabine in elderly patients with advanced colorectal cancer: clinical outcome and subgroup analysis according to KRAS status from a Spanish TTD Group Study. Oncologist 17:339–345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kienle D, Dietrich D, Ribi K, Wicki A, Quagliata L, Winterhalder RC, Koeberle D, Horber D, Bastian S, Kueng M, Saletti P, Helbling D, Baertschi D, Lugli A, Bernhard J, Andrieu C, Roger von Moos R, for the Swiss Group for Clinical Cancer Research (2019) Cetuximab monotherapy and cetuximab plus capecitabine as first-line treatment in older patients with RAS- and BRAF wild-type metastatic colorectal cancer: Results of the multicenter phase II trial SAKK 41/10. J Geriatr Oncol 10:304–310

    Article  PubMed  Google Scholar 

  17. Jonker DJ, O’Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, Berry SR, Krahn M, Price T, Simes RJ, Tebbutt NC, van Hazel G, Wierzbicki R, Langer C, Moore MJ (2007) Cetuximab for the treatment of colorectal cancer. N Engl J Med 357:2040–2048

    Article  CAS  PubMed  Google Scholar 

  18. Balducci L, Beghe C (2000) The application of the principles of geriatrics to the management of the older person with cancer. Crit Rev Oncol Hematol 35:147–154

    Article  CAS  PubMed  Google Scholar 

  19. Extermann M, Aapro M, Bernabei R, Cohen HJ, Droz JP, Lichtman S, Mor V, Monfardini S, Repetto L, Sørbye L, Topinkova E, Task Force on CGA of the International Society of Geriatric Oncology (2005) Use of comprehensive geriatric assessment in older cancer patients: recommendations from the task force on CGA of the International Society of Geriatric Oncology (SIOG). Crit Rev Oncol Hematol 55:241–252

    Article  PubMed  Google Scholar 

  20. Bellera CA, Rainfray M, Mathoulin-Pelissier S, Mertens C, Delva F, Fonck M, Soubeyran PL (2012) Screening older cancer patients: first evaluation of the G-8 geriatric screening tool. Ann Oncol 23:2166–2172

    Article  CAS  PubMed  Google Scholar 

  21. Luciani A, Biganzoli L, Colloca G, Falci C, Castagneto B, Floriani I, Battisti N, Dottorini L, Ferrari D, Fiduccia P, Zafarana E, Del Monte F, Galli F, Monfardini S, Foa P (2015) Estimating the risk of chemotherapy toxicity in older patients with cancer: the role of the Vulnerable Elders Survey-13 (VES-13). J Geriatr Oncol 6:272–279

    Article  PubMed  Google Scholar 

  22. Bouchahda M, Macarulla T, Spano JP, Bachet JB, Lledo G, Andre T, Landi B, Tabernero J, Karaboué A, Domont J, Levi F, Rougier P (2008) Cetuximab efficacy and safety in a retrospective cohort of elderly patients with heavily pretreated metastatic colorectal cancer. Crit Rev Oncol Hematol 67:255–262

    Article  CAS  PubMed  Google Scholar 

  23. Rosati G, Pinto C, Di Fabio F, Chiara S, Lolli IR, Ruggeri EM, Ciuffreda L, Ferrara R, Antonuzzo L, Adua D, Racca P, Bilancia D, Benincasa E, Stroppolo ME, Di Costanzo F (2018) Quality of life, compliance, safety and effectiveness in fit older metastatic colorectal patients with cancer treated in first-line with chemotherapy plus cetuximab: a restrospective analysis from the ObservEr study. J Geriatr Oncol 9:243–248

    Article  PubMed  Google Scholar 

  24. Martinelli E, Cardone C, Troiani T, Normanno N, Pisconti S, Sforza V, Bordonaro AR, Rachiglio AM, Lambiase M, Latiano TP, Modoni G, Cordio S, Giuliani F, Biglietto M, Montesarchio V, Barone C, Tonini G, Cinieri S, Febbraro A, Rizzi D, De Vita F, Orditura M, Colucci G, Maiello E, Ciardiello F (2017) Clinical activity and tolerability of FOLFIRI and cetuximab in elderly patients with metastatic colorectal cancer in the CAPRI-GOIM first-line trial. ESMO Open 1:e000086

    Article  PubMed  PubMed Central  Google Scholar 

  25. Loriot MA, Ciccolini J, Thomas F, Barin-Le-Guellec C, Royer B, Milano G, Picard N, Becquemont L, Verstuyft C, Narjoz C, Schmitt A, Bobin-Dubigeon C, Harle A, Paci A, Poinsignon V, Quaranta S, Evrard A, Hennart B, Broly F, Fonrose X, Lafay-Chebassier C, Wozny AS, Masskouri F, Boyer JC, Etienne-Grimaldi MC (2018) Dihydropyrimidine déhydrogenase (DPD) deficiency screening and securing of fluoropyrimidine-based chemotherapies: update and recommendations of the French GPCO-Unicancer and RNPGx networks. Bull Cancer 105:397–407

    Article  PubMed  Google Scholar 

  26. Zhang X, Yin JF, Zhang J, Kong SJ, Zhang HY, Chen XM (2017) UGT1A1*6 polymorphisms are correlated with irinotecan-induced neutropenia: a systematic review and meta-analysis. Cancer Chemother Pharmacol 80:135–149

    Article  CAS  PubMed  Google Scholar 

  27. Grothey A, Sargent D, Goldberg RM, Schmoll HJ (2004) Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment. J Clin Oncol 22:1209–1214

    Article  CAS  PubMed  Google Scholar 

  28. Lacouture ME, Mitchell EP, Piperdi B, Pillai MV, Shearer H, Iannotti N, Xu F, Yassine M (2010) Skin toxicity evaluation protocol with panitumumab (STEPP), a phase II, open-label, randomized trial evaluating the impact of a pre-Emptive Skin treatment regimen on skin toxicities and quality of life in patients with metastatic colorectal cancer. J Clin Oncol 28:1351–1357

    Article  CAS  PubMed  Google Scholar 

  29. Pinto C, Di Fabio F, Rosati G, Lolli IR, Ruggeri EM, Ciuffreda L, Ferrari D, Lo Re G, Rosti G, Tralongo P, Ferrara R, Alabiso O, Chiara S, Ianniello GP, Frassoldati A, Bilancia D, Campanella GA, Signorelli C, Racca P, Benincasa E, Stroppolo ME, Di Costanzo F (2016) Observational study on quality of life, safety, and effectiveness of first-line cetuximab plus chemotherapy in KRAS wild-type metastatic colorectal cancer patients: the ObservEr Study. Cancer Med 5:3272–3281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Aapro MS, Bohlius J, Cameron DA, Dal Lago L, Donnelly JP, Kearney N, Lyman GH, Pettengell R, Tjan-Heijnen VC, Walewski J, Weber DC, Zielinski C (2011) European Organisation for Research and Treatment of Cancer. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer 47:8–32

    Article  CAS  PubMed  Google Scholar 

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Funding

The survey was possible thanks to a restricted grant of Merck Serono.

Author information

Authors and Affiliations

  1. U.O. Oncologia Medica, Azienda Ospedaliera S. Carlo, Potenza, Italy

    Gerardo Rosati & Domenico Bilancia

  2. U.O. Oncologia Medica, Ospedale “San Giovanni di Dio”, ASL NA 2 NORD, Frattamaggiore, Italy

    Raffaele Addeo

  3. Dipartimento di Oncologia Clinica, Ospedale San Bortolo, AULSS8, Vicenza, Italy

    Giuseppe Aprile

  4. Unità Oncologia Clinica Sperimentale Addome, Dipartimento Assistenziale e di Ricerca dei Percorsi Oncologici del Distretto Addominale, INT Fondazione ‘G. Pascale’, Naples, Italy

    Antonio Avallone

  5. S.C. Oncologia Medica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Silvia Brugnatelli & Sara Delfanti

  6. U.O. Oncologia Medica, Ospedale Umberto I – RAO, Siracusa, Italy

    Gabriella Buccafusca & Paolo Tralongo

  7. Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Naples, Italy

    Chiara Carlomagno

  8. S.C. Oncologia Medica, Ospedale Garibaldi, Catania, Italy

    Stefano Cordio

  9. U.O. Oncologia Medica, Campus Bio-Medico, Università di Roma, Rome, Italy

    Emanuela Dell’Aquila

  10. U.O. Oncologia Medica, OORR, Foggia, Italy

    Maurizio Di Bisceglie

  11. S.O.C. Oncologia Medica, USL Toscana-Centro, Prato, Italy

    Samantha Di Donato

  12. Divisione Oncologia, P.O., Gallipoli, Italy

    Antonio Di Stasi

  13. U.O.C. Oncologia Medica, A.O. “G. Rummo”, Benevento, Italy

    Domenico Germano

  14. Oncologia Medica, Istituto Tumori Giovanni Paolo II, Bari, Italy

    Francesco Giuliani

  15. A.O. S. Croce e Carle, Cuneo, Italy

    Cristina Granetto

  16. Dipartimento di Oncologia Medica, Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy

    Tiziana Pia Latiano

  17. USS Oncologia Geriatrica, Lecce, Italy

    Silvana Leo

  18. Merck Serono S.p.A, Rome, Italy

    Maria Elena Stroppolo & Filippo Venturini

  19. Fullcro S.r.l, Rome, Italy

    Salvatore Bianco

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  1. Gerardo Rosati
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  2. Raffaele Addeo
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  13. Samantha Di Donato
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  14. Antonio Di Stasi
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  15. Domenico Germano
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  16. Francesco Giuliani
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  17. Cristina Granetto
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  18. Tiziana Pia Latiano
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  19. Silvana Leo
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  20. Paolo Tralongo
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  21. Maria Elena Stroppolo
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  22. Filippo Venturini
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  23. Salvatore Bianco
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Correspondence to Gerardo Rosati.

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Author Maria Elena Stroppolo affiliated until August 31st 2018.

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Rosati, G., Addeo, R., Aprile, G. et al. Italian survey on cetuximab-based therapy of elderly patients with metastatic colorectal cancer. Cancer Chemother Pharmacol 84, 1089–1096 (2019). https://doi.org/10.1007/s00280-019-03943-x

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  • DOI: https://doi.org/10.1007/s00280-019-03943-x

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