Magyar Onkológia
Volume/Issue:
Volume 54: Issue 4
Predictive and prognostic factors in the complex treatment of patients with colorectal cancer
Author:
Landherr László School of PhD Studies, University of Medicine and Pharmacy Tg. Mures, Tg. Mures, Romania
Onkoradiológiai Osztály, Fővárosi Uzsoki utcai Kórház, 1145 Budapest, Uzsoki u. 29.

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Pages:
383–394
Online Publication Date:
01 Dec 2010
Publication Date:
01 Dec 2010
Article Category:
Research Article
DOI:
https://doi.org/10.1556/monkol.54.2010.4.13
Keywords:
predictive; prognostic; chemotherapy; targeted therapy; biomarker
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Abstract

Colon cancer is the second most prevalent lethal cancer. The main cause for high mortality rate is that the prognosis for progressed metastatic colon cancer is most unfavorable. Recent data suggest that disease outcome can be further improved by the addition of targeted biological agents to the first- or second-line treatment. As a result of molecularly targeted anti-EGFR therapies (cetuximab and panitumumab) complementing chemotherapy, liver metastases can reduce in size and become operable in certain patients, which can contribute to the complete recovery of the patient. The main problem, however, is the fact that a positive response only occurs in one third of the patients, even in the case of chemotherapy combined protocol, and the side effects are considerable. For the application of individually tailored treatments, it is an urgent need to develop a system of biomarkers that can predict the effect of treatment and provide information about the optimal selection of both chemotherapy and biological treatment. It should be clarified what the most important requirements of a good and reliable biomarker are. As currently there is no precise predictive molecular diagnostics at our disposal, oncologists have to make one of two choices: they treat a large number of patients with anti-EGFR agents which has negative effects on the quality of life and also reduces the patient’s chances of getting appropriate treatment or, if the oncologists refuse to take risks, they omit the use of anti-EGFR treatment in which case those patients for whom this would have been the appropriate treatment are also denied the chance of short-term survival or recovery. Clinical data (response rate, time to progression (TTP) and overall survival (OS)) of 130 colorectal cancer patients have been retrospectively analyzed. Patients have received different chemotherapy protocols in combination with anti-VEGF antibody or with anti-EGFR antibody therapies. EGFR expression was evaluated with immunohistochemistry, KRAS, BRAF and PIK3CA mutations were evaluated by direct sequencing and high resolution melting analysis in the archived formalin-fixed, paraffin-embedded tissue samples. The study found similar efficacy of first-line therapeutic protocols. Protocols combining chemotherapy with biological therapies achieved better overall survival but this difference was not significant (OS: 35.9 versus 36.7 months). The frequency of KRAS mutations was 44% (n=100). None of the KRAS mutant tumors responded to the anti-EGFR monotherapy. TTP in the case of cetuximab monotherapy was twice longer (208 months) than in the KRAS mutant tumors (104 months). One BRAF mutant tumor was also identified (4%) This tumor was also resistant to cetuximab monotherapy. The KRAS and BRAF mutations excluded each other. Except one case, the KRAS status was identical in both the primary tumor and the metastasis. In contrast, PIK3CA mutations were heterogeneous in different tumor samples. In 5 out of 6 cases the mutation status of PIK3CA was different in the primary tumor and the metastasis. New biological therapies provide an additional clinical benefit only for a subset of patients. We need biomarkers to identify these patients. KRAS and most probably BRAF testing can double the efficacy of the anti-EGFR therapies, but we need additional molecular diagnostic tests. PIK3CA is an important candidate but we might need to take biopsy directly from the metastasis or we have to evaluate the circulating tumor cells to judge the molecular status of distant metastasis. Hungarian Oncology 54: 383–394, 2010

  • 1 Landherr, L, Nagykálnai, T, Mészáros, E 2001 A colon carcinoma adjuváns kezelése Uzsoki utcai levelek 7 31–35.

  • 2 Varga, Sz, Póti, Zs, Landherr, L 2001 Előrehaladott colorectalis carcinoma kemoterápiája Uzsoki utcai levelek 7 37–42.

  • 3 Landherr, L 2004 A vastagbéldaganatok korszerű kezelése Orvostovábbképző Szemle Különszám 17–19.

  • 4 Landherr, L, Mészáros, E 2005 Végbél és anális csatorna rákok radio-kemoterápiája Uzsoki utcai levelek 10 37–44.

  • 5 Landherr, L, Klinkó, T, Patonay, P 2007 Colorectalis daganatok perorális kemoterápiájának racionalitása Uzsoki utcai levelek 11 45–50.

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  • 6 Landherr, L 2008 Metastatic colorectal carcinoma (mCRC) specific therapy, VEGF inhibition Orvosi és Gyógyszerészeti Szemle Targu Mures 54 181–184.

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  • 7 Landherr, L 2009 Predictive biomarkers in the treatment of colorectal cancers Orvosi és Gyógyszerészeti Szemle Targu Mures 55 125–128.

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  • 8 Landherr, L, Nagykálnai, T 2009 Időskorú kolorektális daganatos betegek gyógyszeres kezelése Magyar Onkológia 53 97–105.

  • 9 Landherr, L, Nagykálnai, T 2009 A távoli áttétes kolorektális rák (MCRC) első választású kezelésének fejlődése Magyar Onkológia 53 237–246.

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  • 10 Landherr, L 2009 A gyomordaganatok nem sebészi kezelése. Primer májdaganatok és colorectális tumorok okozta májáttétek nem sebészi kezelése GASTRO UPDATE 2009 Gastro Update Alapítvány 127–140.

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  • 11 Landherr, L 2009 Áttétes colorectalis carcinoma (mCRC) célzott biológiai kezelése, az EGF gátlás Orvostudományi értesítő, Targu Mures 82 228–231.

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  • 12 Landherr, L 2000 Gastrointestinális tumorok. Gastro Update Grossarl Melánia Kiadó Budapest 276–287.

  • 13 Landherr, L 2001 Onkológia. Gastro Update 2001 Melánia Kiadó Budapest, 61–64.

  • 14 Landherr, L 2009 A gyomordaganatok nem sebészi kezelése. Primer májdaganatok és colorectális tumorok okozta májáttétek nem sebészi kezelése GASTRO UPDATE 2009 Gastro Update Alapítvány 127–140.

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Cover Magyar Onkológia
Magyar Onkológia
Print ISSN:
0025-0244
Online ISSN:
2060-0399

Magyar Onkológia
Language Hungarian
Size  
Year of
Foundation		 1956
Publication
Programme		  
Volumes
per Year		  
Issues
per Year		  
Founder Magyar Onkológusok Társasága
Founder's
Address		 H-1122 Budapest, Hungary Ráth György u. 7-9.
Publisher Akadémiai Kiadó
Publisher's
Address		 H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Responsible
Publisher		 Chief Executive Officer, Akadémiai Kiadó
ISSN 0025-0244 (Print)
ISSN 2060-0399 (Online)

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