We thank Lippert for his correspondence, in which he points out the importance of resistance testing for chemotherapeutic drugs by means of cell cultures. He is at a loss as to why these tests were not included in the latest S3 guidelines.

Methodologically, it is important to point out the following: guidelines at developmental stage 3 have to explicitly include scientific findings (evidence) in their recommendations (1). In vitro resistance tests have thus far not been sufficiently evaluated for colorectal cancer in terms of their clinical value. On the one hand, it isn’t clear which resistance test has the highest sensitivity and specificity for predicting a non-response to planned chemotherapy. On the other hand, prospective, randomized, studies of possible clinical benefit for patients as a result of additional chemotherapy resistance testing are lacking. To date it has not been prospectively analyzed whether chemoresistance testing can actually help avoid side effects, and whether treatment can thus be individualized. Consequently, there is insufficient evidence on which to base a recommendation for resistance testing.

By contrast, tissue biomarkers—such as the oncogene k-ras—as negative predictive markers for anti-EGFR therapies have been confirmed in the context of several prospective randomized studies in patients with metastatic colorectal cancer (2). Analysis of the k-ras mutation is already included the approval documentation (FDA, EMEA) for the anti-EGFR antibodies panitumumab and cetuximab. This test can be used to identify patients who would not benefit from this treatment and is thus an idea resistance test for anti-EGFR therapy. On the basis of the existing evidence the test has been included in the updated clinical practice guideline for colorectal cancer.
DOI: 10.3238/arztebl.2010.0399b


Prof. Dr. med. Wolff Schmiegel
Medizinische Klinik
Ruhr-Universität Bochum
Knappschaftskrankenhaus
In der Schornau 23–25
44892 Bochum, Germany
meduni-kkh@rub.de

Conflict of interest statement
Professor Schmiegel has received honoraria for speaking from Merck, Roche, Abbott, Amgen, Pfizer, Falk, and Astra-Zeneca. He has also received travel expenses from Roche, Merck, and Astra-Zeneca, and he has received fees for advisory work from Roche, Amgen, and Astra-Zeneca. He has received funding for study projects from Roche and Sanofi-Aventis. Dr. Pox has received speaker honoraria from Falk, Astra-Zeneca, and Hitachi, as well as travel expenses from Roche. Dr. Arnold has received speaker honoraria from Roche, Sanofi-Aventis, Pfizer, Merck, and Amgen, travel expenses from Roche, Sanofi-Aventis, Pfizer, and Merck, as well as study support from Roche, Sanofi-Aventis, Pfizer und Merck. Professor Porschen has received honoraria for speaking from Sanofi-Aventis, Pfizer, und Roche as well as study support from Roche and Sanofi-Aventis. Professor Rödel has received honoraria fro speaking from Roche and Sanofi-Aventis and funding for study projects from Merck. Dr. Reinacher-Schick has received honoraria for speaking from Amgen, Roche, Sanofi-Aventis, and Pfizer, as well as project funding from Roche and Sanofi-Aventis.
1.
B. Kopp IB, Lorenz W, Müller W, Selbmann HK: Methodische Empfehlungen zur Leitlinienerstellung. http://www.awmf.de
2.
Siena S, Cassidy J, Tabernero J, et al.: Randomized phase III study of panitumumab (pmab) with FOLFOX4 compared to FOLFOX4 alone as first-line treatment (tx) for metastatic colorectal cancer (mCRC): PRIME trial. Gastrointestinal Cancer Symposium 2010: Abstract No. 283.
3.
Schmiegel W, Pox C, Arnold D, Porschen R, Rödel C, Reinacher-Schick A: Clinical practice guideline: Colorectal carcinoma—The management of polyps, (neo)adjuvant therapie, and the treatment of metastases [Klinische Leitlinie Kolorektales Karzinom – Polypenmanagement, (neo)adjuvante Therapie, Therapie im metastasierten Stadium]. Dtsch Arztebl Int 2009; 106(51–52): 843–8. VOLLTEXT
1. B. Kopp IB, Lorenz W, Müller W, Selbmann HK: Methodische Empfehlungen zur Leitlinienerstellung. http://www.awmf.de
2. Siena S, Cassidy J, Tabernero J, et al.: Randomized phase III study of panitumumab (pmab) with FOLFOX4 compared to FOLFOX4 alone as first-line treatment (tx) for metastatic colorectal cancer (mCRC): PRIME trial. Gastrointestinal Cancer Symposium 2010: Abstract No. 283.
3. Schmiegel W, Pox C, Arnold D, Porschen R, Rödel C, Reinacher-Schick A: Clinical practice guideline: Colorectal carcinoma—The management of polyps, (neo)adjuvant therapie, and the treatment of metastases [Klinische Leitlinie Kolorektales Karzinom – Polypenmanagement, (neo)adjuvante Therapie, Therapie im metastasierten Stadium]. Dtsch Arztebl Int 2009; 106(51–52): 843–8. VOLLTEXT