Subscribe to RSS
DOI: 10.1055/s-0030-1269440
© Georg Thieme Verlag KG Stuttgart · New York
EGFR-Inhibitoren und Multityrosinkinaseinhibitoren
Interdisziplinäre Behandlung der kutanen NebenwirkungenInterdisciplinary management of cutaneous adverse events of EGFR inhibitors and multityrosine kinase inhibitors in oncologyPublication History
eingereicht: 26.8.2010
akzeptiert: 18.11.2010
Publication Date:
21 December 2010 (online)

Zusammenfassung
Molekular zielgerichtete Therapeutika und hier insbesondere die Inhibitoren des epidermalen Wachstumsfaktorrezeptors (EGFRi) und Multityrosinkinase-Inhibitoren (MTKi) gewinnen einen immer größeren Stellenwert in der onkologischen Therapie. Die Nebenwirkungen unterscheiden sich deutlich von denen der konventionellen Chemotherapie. Vor allem kutane Nebenwirkungen stellen dosis- oder therapielimitierende Ereignisse dar. Eine genaue Kenntnis der Nebenwirkungen sowie ein enger Austausch des Dermatologen mit dem behandelnden Onkologen und dem Hausarzt, eine detaillierte Patientenaufklärung und ein fundiertes Nebenwirkungsmanagement sind Grundbausteine für eine erfolgreiche Therapie mit EGFRi und MTKi. Gemeinsame dermatologische und onkologische Schwerpunktsprechstunden helfen bei der Behandlung von schweren Fällen kutaner Toxizitäten, der Entwicklung von neuen Therapiestrategien und sind insbesondere zur Begleitbehandlung von Patienten in klinischen Studien essentiell.
Abstract
Molecular targeted therapies – particularly epidermal growth factor receptor inhibitors (EGFRi) and multi tyrosine kinase-inhibitors (MTKi) – continually gain importance in oncology treatment. Adverse events differ greatly from those of conventional chemotherapy; especially cutaneous adverse events often constitute dose-limiting or therapy-limiting events. Knowledge of possible adverse events and close interaction between the dermatologist, the oncologist and the patient’s family physician, a detailed patient education and a well-founded adverse event management are mandatory for the treatment with EGFRi and MTKi. Interdisciplinary outpatient clinics specialised on the treatment of these adverse events assist with the treatment of severe cases, the development of new therapeutic strategies and are essential for the concomitant treatment of patients treated with new targeted drugs within clinical trials.
Schlüsselwörter
EGFRi - MTKi - Tyrosinkinaseinhibitoren - kutane Nebenwirkungen - targeted therapy - Nebenwirkungsmanagement
Keywords
EGFRi - MTKi - tyrosinkinase inhibitors - cutaneous adverse events - targeted therapy - adverse event management
Literatur
- 1
Arnault J P, Wechsler J, Escudier B, Spatz A, Tomasic G, Sibaud V, Aractingi S, Grange J D, Poirier-Colame V, Malka D, Soria J C, Mateus C, Robert C.
Keratoacanthomas and squamous cell carcinomas
in patients receiving sorafenib.
J Clin Oncol.
2009;
27
e59-61
MissingFormLabel
- 2
Boone S L, Rademaker A, Liu D, Pfeiffer C, Mauro D J, Lacouture M E.
Impact and
management of skin toxicity associated with anti-epidermal growth
factor receptor therapy: survey results.
Oncology.
2007;
72
152-159
MissingFormLabel
- 3
Chou L S, Garey J, Oishi K, Kim E.
Managing dermatologic toxicities
of epidermal growth factor receptor inhibitors.
Clin Lung
Cancer.
2006;
8, Suppl 1
S15-22
MissingFormLabel
- 4
Cortesi E, DePasquale C, D’Auria G. et al .
Management of cutaneous adverse effects
during treatment with ZD1838 in advanced non-small cell lung cancer
(NSCLC): surprising efficacy of early local treatment.
Proc
Am Assoc Cancer Res.
2004;
22
abstr 7100
MissingFormLabel
- 5
Dancey J, Sausville E A.
Issues and progress
with protein kinase inhibitors for cancer treatment.
Nat
Rev Drug Discov.
2007;
2
296-313
MissingFormLabel
- 6
Dasanu C A, Alexandrescu D T, Dutcher J.
Yellow skin discoloration associated with
sorafenib use for treatment of metastatic renal cell carcinoma.
South Med J.
2007;
100
328-330
MissingFormLabel
- 7
Degen A, Alter M, Schenck F, Satzger I, Volker B, Kapp A, Gutzmer R.
The hand-foot-syndrome associated with medical tumor therapy – classification
and management.
J Dtsch Dermatol Ges.
2010;
8
652-661
MissingFormLabel
- 8
Dubauskas Z, Kunishige J, Prieto V G, Jonasch E, Hwu P, Tannir N M.
Cutaneous squamous
cell carcinoma and inflammation of actinic keratoses associated
with sorafenib.
Clin Genitourin Cancer.
2009;
7
20-23
MissingFormLabel
- 9
Eilers Jr R E, Gandhi M, Patel J D, Mulcahy M F, Agulnik M, Hensing T, Lacouture M E.
Dermatologic infections in cancer
patients treated with epidermal growth factor receptor inhibitor
therapy.
J Natl Cancer Inst.
2010;
102
47-53
MissingFormLabel
- 10
Eiling E, Brandt M, Schwarz T, Hauschild A.
Pimecrolimus: a novel treatment
for cetuximab-induced papulopustular eruption.
Arch Dermatol.
2008;
144
1236-1238
MissingFormLabel
- 11
Fox L P.
Nail toxicity associated with epidermal growth factor receptor
inhibitor therapy.
J Am Acad Dermatol.
2007;
56
460-465
MissingFormLabel
- 12
Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard J Y, Nishiwaki Y, Vansteenkiste J, Kudoh S, Rischin D, Eek R, Horai T, Noda K, Takata I, Smit E, Averbuch S, Macleod A, Feyereislova A, Dong R P, Baselga J.
Multi-institutional randomized phase II
trial of gefitinib for previously treated patients with advanced
non-small-cell lung cancer (The IDEAL 1 Trial) [corrected].
J Clin Oncol.
2003;
21
2237-2246
MissingFormLabel
- 13
Golub L M, Lee H M, Ryan M E, Giannobile W V, Payne J, Sorsa T.
Tetracyclines
inhibit connective tissue breakdown by multiple non-antimicrobial
mechanisms.
Adv Dent Res.
1998;
12
12-26
MissingFormLabel
- 14
Grandinetti C A, Goldspiel B R.
Sorafenib
and sunitinib: novel targeted therapies for renal cell cancer.
Pharmacotherapy.
2007;
27
1125-1144
MissingFormLabel
- 15
Hong D S, Reddy S B, Prieto V G, Wright J J, Tannir N M, Cohen P R, Diwan A H, Evans H L, Kurzrock R.
Multiple
squamous cell carcinomas of the skin after therapy with sorafenib
combined with tipifarnib.
Arch Dermatol.
2008;
144
779-782
MissingFormLabel
- 16
Hu J C, Sadeghi P, Pinter-Brown L C, Yashar S, Chiu M W.
Cutaneous side effects of epidermal growth
factor receptor inhibitors: clinical presentation, pathogenesis,
and management.
J Am Acad Dermatol.
2007;
56
317-326
MissingFormLabel
- 17
Jantzem H, Dupre-Goetghebeur D, Spindler P, Merrer J.
[Sorafenib-induced
multiple eruptive keratoacanthomas].
Ann Dermatol
Venereol.
2009;
136
894-897
MissingFormLabel
- 18
Jatoi A, Rowland K, Sloan J A, Gross H M, Fishkin P A, Kahanic S P, Novotny P J, Schaefer P L, Johnson D B, Tschetter L K, Loprinzi C L.
Tetracycline to
prevent epidermal growth factor receptor inhibitor-induced skin rashes:
results of a placebo-controlled trial from the North Central Cancer
Treatment Group (N03CB).
Cancer.
2008;
113
847-853
MissingFormLabel
- 19
Kong H H, Cowen E W, Azad N S, Dahut W, Gutierrez M, Turner M L.
Keratoacanthomas
associated with sorafenib therapy.
J Am Acad Dermatol.
2007;
56
171-172
MissingFormLabel
- 20
Krakauer T, Buckley M.
Doxycycline is anti-inflammatory
and inhibits staphylococcal exotoxin-induced cytokines and chemokines.
Antimicrob Agents Chemother.
2003;
47
3630-3633
MissingFormLabel
- 21
Kwon E J, Kish L S, Jaworsky C.
The histologic spectrum of epithelial neoplasms induced by sorafenib.
J Am Acad Dermatol.
2009;
61
522-527
MissingFormLabel
- 22
Lacouture M E.
Mechanisms of cutaneous toxicities to EGFR inhibitors.
Nat
Rev Cancer.
2006;
6
803-812
MissingFormLabel
- 23
Lacouture M E, Basti S, Patel J, Benson A.
The SERIES clinic: an interdisciplinary
approach to the management of toxicities of EGFR inhibitors.
J
Support Oncol.
2006;
4
236-238
MissingFormLabel
- 24
Lacouture M E, Boerner S A, Lorusso P M.
Non-rash skin toxicities associated with
novel targeted therapies.
Clin Lung Cancer.
2006;
8 Suppl 1
S36-42
MissingFormLabel
- 25
Lacouture M E, Desai A, Soltani K, Petronic-Rosic V, Laumann A E, Ratain M J, Stadler W M.
Inflammation of actinic keratoses
subsequent to therapy with sorafenib, a multitargeted tyrosine-kinase
inhibitor.
Clin Exp Dermatol.
2007;
31
783-785
MissingFormLabel
- 26
Lacouture M E, Melosky B L.
Cutaneous
reactions to anticancer agents targeting the epidermal growth factor
receptor: a dermatology-oncology perspective.
Skin Therapy
Lett.
2007;
12
1-5
MissingFormLabel
- 27
Lacouture M E, Wu S, Robert C, Atkins M B, Kong H H, Guitart J, Garbe C, Hauschild A, Puzanov I, Alexandrescu D T, Anderson R T, Wood L, Dutcher J P.
Evolving strategies for the management
of hand-foot skin reaction associated with the multitargeted kinase
inhibitors sorafenib and sunitinib.
Oncologist.
2008;
13
1001-1011
MissingFormLabel
- 28
Li T, Perez-Soler R.
Skin toxicities associated
with epidermal growth factor receptor inhibitors.
Target
Oncol.
2009;
4
107-119
MissingFormLabel
- 29
LoRusso P.
Toward evidence-based management of the dermatologic effects
of EGFR inhibitors.
Oncology (Williston Park).
2009;
23
186-194
MissingFormLabel
- 30
Marquez C B, Smithberger E E, Bair S M, Wenham R M, Fenske N A, Glass L F, Cherpelis B S.
Multiple
keratoacanthomas arising in the setting of sorafenib therapy: novel
chemoprophylaxis with bexarotene.
Cancer Control.
2009;
16
66-69
MissingFormLabel
- 31
Melosky B, Burkes R, Rayson D, Alcindor T, Shear N, Lacouture M.
Management of skin
rash during EGFR-targeted monoclonal antibody treatment for gastrointestinal
malignancies: Canadian recommendations.
Curr Oncol.
2009;
16
16-26
MissingFormLabel
- 32
Mitchell E P, Lacouture M, Shearer H. et al .
Updated results of STEPP, a phase 2, open-label
study of pre-emptive versus reactive skin toxicity treatment in
metastatic colorectal cancer (mCRC) patients receiving panitumumab+ FOLFIRI
or irinotecan-only chemotherapy as second-line treatment.
Ann
Oncol.
2008;
19
(suppl)
O-021
MissingFormLabel
- 33
Perez-Soler R.
Can rash associated with HER1/EGFR inhibition be used
as a marker of treatment outcome?.
Oncology (Williston
Park).
2003;
17
23-28
MissingFormLabel
- 34
Perez-Soler R, Chachoua A, Hammond L A, Rowinsky E K, Huberman M, Karp D, Rigas J, Clark G M, Santabarbara P, Bonomi P.
Determinants of tumor
response and survival with erlotinib in patients with non – small-cell
lung cancer.
J Clin Oncol.
2003;
22
3238-3247
MissingFormLabel
- 35
Perez-Soler R, Saltz L.
Cutaneous adverse effects
with HER1/EGFR-targeted agents: is there a silver lining?.
J Clin Oncol.
2005;
23
5235-5246
MissingFormLabel
- 36
Perez-Soler R, Zou Y, Li T. et
al .
Topical vitamin K3 (Vit K3, Menadione) prevents
erlotinib and cetuximab-induced EGFR inhibition in the skin.
J
Clin Oncol.
2003;
24
3036a
MissingFormLabel
- 37
Porta C, Paglino C, Imarisio I, Bonomi L.
Uncovering Pandora’s
vase: the growing problem of new toxicities from novel anticancer
agents.
The case of sorafenib and sunitinib Clin Exp Med.
2007;
7
127-134
MissingFormLabel
- 38
Potthoff K, Hofheinz R, Hassel J C, Volkenandt M, Lordick F, Hartmann J T, Karthaus M, Riess H, Lipp H P, Hauschild A, Trarbach T, Wollenberg A.
Interdisciplinary
management of EGFR-inhibitor-induced skin reactions: a German expert
opinion.
Ann Oncol.
2010;
[Epub
ahead of print]
MissingFormLabel
- 39
Robert C, Soria J C, Spatz A, Le Cesne A, Malka D, Pautier P, Wechsler J, Lhomme C, Escudier B, Boige V, Armand J P, Le Chevalier T.
Cutaneous side-effects
of kinase inhibitors and blocking antibodies.
Lancet Oncol.
2005;
6
491-500
MissingFormLabel
- 40
Roe E, Garcia Muret M P, Marcuello E, Capdevila J, Pallares C, Alomar A.
Description
and management of cutaneous side effects during cetuximab or erlotinib
treatments: a prospective study of 30 patients.
J Am Acad
Dermatol.
2006;
55
429-437
MissingFormLabel
- 41
Scope A, Agero A L, Dusza S W, Myskowski P L, Lieb J A, Saltz L, Kemeny N E, Halpern A C.
Randomized
double-blind trial of prophylactic oral minocycline and topical
tazarotene for cetuximab-associated acne-like eruption.
J
Clin Oncol.
2007;
25
5390-5396
MissingFormLabel
- 42
Segaert S, Tabernero J, Chosidow O, Dirschka T, Elsner J, Mancini L, Maughan T, Morere J F, Santoro A, Sobrero A, Van Cutsem E, Layton A.
The management of skin
reactions in cancer patients receiving epidermal growth factor receptor
targeted therapies.
J Dtsch Dermatol Ges.
2005;
3
599-606
MissingFormLabel
- 43
Segaert S, Van Cutsem E.
Clinical signs, pathophysiology
and management of skin toxicity during therapy with epidermal growth
factor receptor inhibitors.
Ann Oncol.
2005;
16
1425-1433
MissingFormLabel
- 44
Smith K J, Haley H, Hamza S, Skelton H G.
Eruptive keratoacanthoma-type
squamous cell carcinomas in patients taking sorafenib for the treatment
of solid tumors.
Dermatol Surg.
2009;
35
1766-1770
MissingFormLabel
- 45
Tsao A S, Kantarjian H, Cortes J, O’Brien S, Talpaz M.
Imatinib mesylate causes hypopigmentation in the skin.
Cancer.
2003;
98
2483-2487
MissingFormLabel
- 46
Valeyrie L, Bastuji-Garin S, Revuz J, Bachot N, Wechsler J, Berthaud P, Tulliez M, Giraudier S.
Adverse cutaneous
reactions to imatinib (STI571) in Philadelphia chromosome-positive
leukemias: a prospective study of 54 patients.
J Am Acad
Dermatol.
2003;
48
201-206
MissingFormLabel
- 47
Wollenberg A, Kroth J, Hauschild A, Dirschka T.
Hautreaktionen unter EGFR-Inhibitoren – Klinik
und Management.
Dtsch Med Wochenschr.
2010;
135
149-154
MissingFormLabel
Prof. Dr. Dirk Schadendorf
Klinikdirektor
Abteilung für Dermatologie
Universitätsklinik
Essen
Hufelandstr. 55
45122 Essen
Phone: 0201/723 4342
Fax: 0201/723
5935
Email: dirk.schadendorf@uk-essen.de