The use of anti-EGFR monoclonal antibodies-EGFR blockers in the comprehensive treatment of metastatic colorectal cancer with or without the surgical removal of metastases


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Abstract

Clinical data on the efficacy and safety of cetuximab and panitumumab in 87 patients in the 1-4 lines of drug therapy for metastatic colorectal cancer (mCRC) with wild-type RAS with and without surgical removal of metastases were analyzed. Anti-EGFR drugs were prescribed for patients in the first line of therapy in 64.4%, in the second line - 14.9%, in the third line - 13.8% and 6.9% - in the fourth line. 14.9% of patients continued anti-EGFR therapy after progression during 2-3 lines (with the change of cytostatics). The use of anti-EGFR drugs in treatment for mCRC was shown to provide satisfactory results of overall survival rate and progression-free survival. The most important result of the analysis is the revealed significant increase in median overall survival from 13.4±1.6 to 18.7±2.3 months (p = 0.04838) in patients who had anti-EGFR therapy and chemotherapy with surgical treatment of distant resectable metastases. Manifestations specific for anti-EGFR drugs dermal toxicity were tolerable and managed with medical correction.Of the patients who has been undergone to cytoreductive surgical interventions for resectable metastases, clinically significant complications of the surgery were observed in 17.2% ofpatients.

About the authors

O. I Kit

Russian Scientific Research Institute of Oncology

Rostov-on-Don, 344037, Russian Federation

L. Yu Vladimirova

Russian Scientific Research Institute of Oncology

Rostov-on-Don, 344037, Russian Federation

Nataliya A. Abramova

Russian Scientific Research Institute of Oncology

Email: pylulkin@mail.ru
MD, PhD, Senior Researcher of the Department of Drug Treatment of Tumors Rostov-on-Don, 344037, Russian Federation

A. E Storozhakova

Russian Scientific Research Institute of Oncology

Rostov-on-Don, 344037, Russian Federation

E. A Kalabanova

Russian Scientific Research Institute of Oncology

Rostov-on-Don, 344037, Russian Federation

S. N Kabanov

Russian Scientific Research Institute of Oncology

Rostov-on-Don, 344037, Russian Federation

I. L Popova

Russian Scientific Research Institute of Oncology

Rostov-on-Don, 344037, Russian Federation

K. A Novoselova

Russian Scientific Research Institute of Oncology

Rostov-on-Don, 344037, Russian Federation

N. M Tkhanovskaya

Russian Scientific Research Institute of Oncology

Rostov-on-Don, 344037, Russian Federation

A. A Agieva

Russian Scientific Research Institute of Oncology

Rostov-on-Don, 344037, Russian Federation

T. A Snezhko

Russian Scientific Research Institute of Oncology

Rostov-on-Don, 344037, Russian Federation

N. Y Samaneva

Russian Scientific Research Institute of Oncology

Rostov-on-Don, 344037, Russian Federation

References

  1. Jemal A. Global cancer statistics. C.A. Cancer J. Clin. 2011; 2 (61): 69-90.
  2. Беляева А.В. Мутации в гене K-ras у больных колоректальным раком: эпидемиология и клиническое значение: Дисс. ...канд. мед. наук. СПб.; 2012.
  3. Архипова О.Е., Черногубова Е.А., Лихтанская Н.В., Тарасов В.А., Кит О.И., Матишов Д.Г. Анализ встречаемости онкологических заболеваний в ростовской области. Пространственно-временная статистика Фундаментальные исследования. 2013; 7-3: 504-10.
  4. Кит О.И. Проблема колоректального рака в начале ХХI века: достижения и перспективы. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2013; 23 (3): 65-71.
  5. Allegra C.J., Jessup J.M., Somerfield M.R. et al. American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J. Clin. Oncol. 2009; 27 (12): 2091-6.
  6. Amado R., Wolf M., Peeters M. et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J. Clin. Oncol. 2008; 26: 1626-34.
  7. Van Cutsem E., Peeters M., Siena S. et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J. Clin. Oncol. 2007; 25: 1658-64.
  8. Владимирова Л.Ю., Геворкян Ю.А., Абрамова Н.А. и др. Оценка эффективности и токсичности моноклонального антитела к EGFR панитумумаба при колоректальном раке. В кн.: VII Съезд онкологов и радиологов стран СНГ. 2012.
  9. Van Cutsem E., Humblet Y. et al. Cetuximab dose-escalation study in patients with nCRC with no or slight skin reaction on cetuximab standard dose treatment (EVEREST): preliminary PK and efficacy date of a randomized study. In: Proceedings of ASCO 2007. 2008: Abstr. 237.
  10. Peeters M., Price T., Hotko Y. et al. Randomized phase 3 study of panitumumab with FOLFIRI vs FOLFIRI alone as second-line treatment (tx) in patients (pts) with metastatic colorectal cancer (mCRC). Eur. J. Cancer. 2009; 7 (3, Suppl.): 14LBA.
  11. Price T. et al. ASPECCT: a randomized, multicenter, open-label, phase 3 study of panitumumab (pmab) vs cetuximab (cmab) for previously treated wild-type (WT) KRAS metastatic colorectal cancer (mCRC). In: The European Cancer Congress 2013. Sep 29. 2014: Abstr. 18.
  12. Stintzing S., Jung A., Rossius L. et al: Analysis of KRAS/NRAS and BRAF mutations in FIRE-3: A randomized phase III study of FOLFIRI plus cetuximab or bevacizumab as first-line treatment for wild-type (WT) KRAS (exon 2) metastatic colorectal cancer (mCRC) patients. In: The European Cancer Congress 2013, Sep. 29. 2013: Abstr. 17.
  13. Cascinu S., Rosati G., Nasti G., Lonardi S. et al. A phase III multicenter trial comparing two different sequences of second/third line therapy (irinotecan/cetuximab followed by FOLFOX-4 vs. FOLFOX-4 followed by irinotecan/cetuximab in K-RAS wt metastatic colorectal cancer (mCC) patients refractory to FOLFIRI/Bevacizumab. Eur. J. Cancer. 2015; 51 (Suppl. S3): S329.
  14. Abramova N., Vladimirova L.Yu., Kit O.I. Monoclonal antibodies against EGFR-receptors in metastatic colorectal cancer (mCRC) treatment: comparative tolerability and efficacy of Panitumumab (P) and Cetuximab (C). In: ASCO Annual Meeting. 2014. Abstr. 1070.
  15. Douillard J., Siena S., Cassidy J. et al. Randomized phase 3 study of panitumumab with FOLFOX4 vs FOLFOX4 alone as firstline treatment in patients with metastatic colorectal cancer: the PRIME trial. Eur. J. Cancer. 2009; 7 (3, Suppl.): 10LBA.
  16. Humblet Y., Peeters M., Siena S. et al. Association of skin toxicity (ST) severity with clinical outcomes and health-related quality of life (HRQoL) with panitunumab (Pmab). In: American Society of Clinical Oncology. Chicago; 2007: Abstr. 4038.
  17. Vladimirova L.Y., Kit O.I., Nikipelova E.A. et al. Resilts of monoclonal antibodies against EGFR-receptors application in patients with metastatic colorectal cancer. J. Clin. Oncol. 2013; 31 (Suppl. 15: 49 Annual Meeting of ASCO): 800S. e19047.
  18. Варламова С.Е., Антимоник Н.Ю., Козлова Н.М., Макеев Ю.М., Бердов Б.А., Болотина Л.В. и др. Отечественный опыт профилактики и лечения проявлений кожной токсичности у пациентов мКРР, получающих ингибиторы EGFR, на примере панитумумаба. Проект RUSSCO по разработке рекомендаций по коррекции дерматологических реакций у пациентов, получающих терапию ингибиторами EGFR. Злокачественные опухоли. 2013; 3: 42-51.
  19. Folprecht G., Gruenberger T., Bechstein W.O. et al. Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial. Lancet Oncol. 2010; 11 (1): 38-47.
  20. Kopetz S., Chang G.J., Overman M.J. et al. Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J. Clin. Oncol. 2009; 27 (22): 3677-83.
  21. Nordlinger B., van Cutsem E., Gruenberger T. et al. Combination of surgery and chemotherapy and the role of targeted agents in the treatment of patients with colorectal liver metastases: recommendations from an expert panel. Ann. Oncol. 2009; 20 (6): 985-92.

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