Kernaussagen
Behandlungsstrategien
Die Einführung der neuen Chemotherapeutika Irinotecan und Oxaliplatin hat neben einer
Verbesserung der Behandlungsergebnisse auch eine Zunahme der therapeutischen Komplexität
mit sich gebracht, welche zwingend die enge interdisziplinäre Zusammenarbeit der beteiligten
Fachdisziplinen erfordert.
Die systemische Behandlung des kolorektalen Karzinoms verfolgt 3 zentrale Ziele: die
Prävention des Rezidivs nach kurativer Resektion (adjuvante Therapie), die Lebensverlängerung
und Symptomkontrolle bei Patienten mit metastasierter Erkrankung (palliative Therapie)
und das erreichen einer sekundären kurativen Resektabilität oder die Verlängerung
des rezidivfreien Überlebens durch eine präoperative Behandlung (neoadjuvante Therapie).
Adjuvante Therapie des KRK
Oxaliplatin ist dem Irinotecan in der adjuvanten Therapie überlegen, weshalb außerhalb
von Studien FOLFOX4/6 die Standardtherapie im Stadium III darstellt.
Ist eine Kombinationschemotherapie nicht möglich, sollte Capecitabin eingesetzt werden.
Zielgerichtete biologische Substanzen sollten derzeit nur in Studien zum Einsatz kommen.
Bei Patienten im Stadium II kann bei Hochrisikokonstellation (Perforation, Ileus,
T4, G3, V1 oder weniger als 10 entnommene Lymphknoten) eine adjuvante Therapie erwogen
werden.
Systemische Therapie des fortgeschrittenen KRK
Ein wirklicher therapeutischer Fortschritt im Bereich der palliativen Therapie konnte
mit der Einführung der neuen Chemotherapeutika Irinotecan und Oxaliplatin sowie der
neuen biologischen Wirkstoffe Cetuximab und Bevacizumab erzielt werden.
Nicht welche Kombinationschemotherapie als Erstlinientherapie verabreicht wird, bestimmt
die Prognose des Patienten, sondern ob der Patient während seines Krankheitsverlaufs
alle zur Verfügung stehenden aktiven Substanzen erhält.
„Stopp-and-Go-Strategien” können die Nebenwirkungen reduzieren und damit die Lebensqualität
der Patienten während der Chemotherapie verbessern.
Literatur
- 1
Boyle P, Ferlay J.
Cancer incidence and mortality in Europe, 2004.
Ann Oncol.
2005;
16
481-488; Epub 2005 Feb 17
- 2
Russo M W, Wei J T, Thiny M T. et al .
Digestive and liver diseases statistics, 2004.
Gastroenterology.
2004;
126(5)
1448-1453
- 3
Jemal A, Murray T, Ward E. et al .
Cancer statistics, 2005.
CA Cancer J Clin.
2005;
55
10-30
- 4
Schmiegel W, Pox C, Adler G.
S3-Leitlinienkonferenz „Kolorektales Karzinom” 2004.
Z Gastroenterol.
2004;
42
1129-1177
- 5
Gill S, Loprinzi C L, Sargent D J. et al .
Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon
cancer: who benefits and by how much?.
J Clin Oncol.
2004;
22
1797-1806
- 6
Benson A B, Schrag D, Somerfeld M R. et al .
American Society of Clinical Oncology recommendations on adjuvant chemotherapy for
stage II colon cancer.
J Clin Oncol.
2004;
22
3408-3419
- 7
Figueredo A, Charette M, Maroun J. et al .
Adjuvant therapy for stage II colon cancer: a systematic review from the cancer care
Ontario program in evidence-based care’s gastrointestinal cancer disease site group.
J Clin Oncol.
2004;
22
3395-3407
- 8
Gray R G, Barnwell J, Hills R. et al .
QUASAR: A randomized study of adjuvant chemotherapy (CT) vs observation including
3238 colorectal cancer patients.
J Clin Oncol.
2004;
22
3501
- 9
Saltz L B, Niedzwiecki D, Hollis D. et al .
Irinotecan plus fluorouracil/leucovorin (IFL) versus fluorouracil/leucovorin alone
(FL) in stage III colon cancer (intergroup trial CALGB C89803).
J Clin Oncol.
2004;
22
S3500
- 10
van Cutsem E, Labianca R, Hossfeld D. et al .
Randomized phase III trial comparing infused irinotecan/5-fluorouracil (5-FU)/folinic
acid (IF) versus 5-FU/FA (F) in stage III colon cancer patients (pts).
(PETACC 3) Proc Am Soc Clin Oncol.
2005;
Abstract
LBA8
- 11
Andre T, Boni C, Mounedji-Boudiaf L. et al .
Oxaliplatin, Fluorouracil, and Leucovorin as adjuvant treatment for colon cancer.
N Engl J Med.
2004;
350
2343-2351
- 12 deGramont A, Boni C, Navarro M. et al .
Oxaliplatin/5FU/LV in the adjuvant treatment of stage II and stage III colon cancer:
efficacy results with a median follow-up of 4 years. In: Proceedings of the 2005 Gastrointestinal Cancers Symposium. 2005: 167
- 13
Wolmark N, Wieand H S, Kuebler J P. et al .
A phase III trial comparing FULV to FULV + oxaliplatin in stage II or III carcinoma
of the colon: Results of NSABP Protocol C-07.
Proc Am Soc Clin Oncol.
2005;
Abstract
LBA3500
- 14
Twelves C, Wong A, Nowacki M. et al .
Updated efficacy findings from the X-ACT phase III trial of capecitabine (X) vs. bolus
5-FU/LV as adjuvant therapy for patients (pts) with Dukes’ C colon cancer.
Proc Am Soc Clin Oncol.
2005;
Abstract
3521
- 15
Cunningham D, Pyrhonen S, James R D. et al .
Randomized trial of irinotecan plus supportive care versus supportive care alone after
fluoruracil failure for patients with metastatic colorectal cancer.
Lancet.
1998;
352
1413-1418
- 16
Douillard J Y, Cunningham D, Roth A D. et al .
Irinotecan combined with fluorouracil compared with fluorouracil alone as first line
treatment for metastatic colorectal cancer: a multicenter randomized trial.
Lancet.
2000;
355
1041-1047
- 17
Saltz L B, Cox J V, Blanke C. et al .
Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer.
NEJM.
2000;
343
905-914
- 18
Rothenberg M L, Oza A M, Bigelow R H. et al .
Superiority of Oxaliplatin and Fluoruracil - Leucovorin compared with either therapy
alone in patients with progressive colorectal cancer after Irinotecan and Fluoruracil
- Leucovorin: Interim Results of a phase III trial.
J Clin Oncol.
2003;
21
2059-2069
- 19
Grothey A, Deschler B, Kroening H. et al .
Phase III study of bolus 5-fluoruracil (5-FU)/ folic acid (FA) (Mayo) vs. weekly high
dose 24 h5-FU infusion/FA + oxaliplatin (OXA) in advanced colorectal cancer (ACRC).
Proc Am Soc Clin Oncol.
2002;
21
129a
- 20
Goldberg R M, Sargent D J, Morton R F. et al .
A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin
combinations in patients with previously untreated metastatic colorectal cancer.
J Clin Oncol.
2004;
22
23-30
- 21
Hoff P M, Ansari R, Batist G. et al .
Comparison of oral capecitabine versus intravenous fluoruracil plus leucovorin as
first line therapy in 605 patients with metastatic colorectal cancer: Results of a
randomized phase III study.
J Clin Oncol.
2001;
19
2282-2292
- 22
van Cutsem E, Twelfes C, Cassidy J. et al .
Oral capecitabine compared with intravenous fluoruracil plus leucovorin in patients
with metastatic colorectal cancer: Results of a large phase III study.
J Clin Oncol.
2001;
19
4097-4106
- 23
Bajetta E, Di Bartolomeo M, Marian L. et al .
Randomized multicenter Phase II trial of two different schedules of irinotecan combined
with capecitabine as first line treatment in metastatic colorectal carcinoma.
Cancer.
2004;
100
279-287
- 24
Grothey A, Jordan K, Kellner O. et al .
Randomized phase II trial of capecitabine plus irinotecan (CapIri) vs capecitabine
plus oxaliplatin (CaPox) as first line therapy of advanced colorectal cancer (ACRC).
Proc Am Soc Clin Oncol.
2003;
23
255
- 25
Arkenau H, Schmoll H, Kubicka S. et al .
Infusional 5-fluorouracil/folinic acid plus oxaliplatin (FUFOX) versus capecitabine
plus oxaliplatin (CAPOX) as first line treatment of metastatic colorectal cancer (MCRC):
Results of the safety and efficacy analysis.
ASCO.
2005;
Abstract
3507
- 26
Kohne C, de Greve J, Bokemeyer C. et al .
Capecitabine plus irinotecan versus 5-FU/FA/irinotecan ± celecoxib in first line treatment
of metastatic colorectal cancer. Safety results of the prospective multicenter EORTC
phase III study 40 015.
ASCO.
2005;
Abstract
3525
- 27
Grothey A, Sargent D, Goldberg R M. et al .
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.
2004;
22
1209-1214
- 28
Cunningham D, Humblet Y, Siena S. et al .
Cetuximab (C225) alone or in combination with irinotecan (CPT 11) in patients with
epidermal growth factor receptor (EGFR) positive, irinotecan-refractory metastatic
colorectal cancer (MCRC).
Proc Am Soc Clin Oncol.
2003;
22
253
- 29
Lenz H J, Mayer R J, Gold P J. et al .
Activity of cetuximab in patients with colorectal cancer refractory to both irinotecan
and oxaliplatin.
JCO.
2004;
22
3510
- 30
Rosenberg A H, Loehrer P J, Needle M N. et al .
Erbitux (IMC-C225) plus weekly irinotecan (CPT-11), fluorouracil (5FU) and leucovorin
(LV) in colorectal cancer (CRC) that expresses the epidermal growth factor receptor
(EGFr).
ASCO.
2002;
Abstract
536
- 31
Rougier P, Raoul J L, van Laethem J L. et al .
Cetuximab + FOLFIRI as first-line treatment for metastatic colorectal CA.
JCO.
2004;
22
3513
- 32
Tabernero J M, van Cutsem E, Sastre J. et al .
An international phase II study of cetuximab in combination with oxaliplatin/5-fluorouracil
(5-FU)/folinic acid (FA) (FOLFOX-4) in the first-line treatment of patients with metastatic
colorectal cancer (CRC) expressing Epidermal Growth Factor Receptor (EGFR). Preliminary
results.
JCO.
2004;
22
3512
- 33
Hurwitz H, Fehrenbacher L, Cartwright T. et al .
Bevacizumab (a monoclonal antibody to vascular endothelial growth factor) prolongs
survival in first line colorectal cancer (CRC): results of a phase III trial of bevacizumab
in combination with bolus IFL (irinotecan, 5-fluoruracil, leucovorin) as first line
therapy in subjects with metastatic CRC.
Proc Am Soc Clin Oncol.
2003;
22
3636
- 34
Giantonio B J, Catalano P J, Meropol N J.
High-dose bevacizumab improves survival when combined with FOLFOX4 in previously treated
advanced colorectal cancer: Results from the Eastern Cooperative Oncology Group (ECOG)
study E3200.
ASCO.
2005;
Abstract
2
- 35
Goss G D, Stewart D J, Hirte H. et al .
Initial results of part 2 of a phase I/II pharmacokinetic, pharmacodynamic and biological
activity study of ZD 1839.
Proc Am Soc Clin Oncol.
2002;
21
16a
- 36
Oza A M, Townsley C A, Siu L L. et al .
Phase II study of erlotinib (OSI-774) in patients with metastatic colorectal cancer.
Proc Am Soc Clin Oncol.
2003;
22
196a
- 37
Cho C D, Fisher G A, Halsey J. et al .
A phase II study of Geftinib in combination with FOLFOX4 in patients with metastatic
colorectal cancer.
Proc Am Soc Clin Oncol.
2003;
22
265a
- 38
Messersmith W A, Laheru D A, Senzer N N. et al .
Phase I trial of irinotecan, infusional 5-fluorouracil, and leucovorin (FOLFIRI) with
erlotinib (OSI-774): early termination due to increased toxicities.
Clin Cancer Res.
2004;
10
6522-6527
- 39
Hecht R, Trarbach T, Jaeger E, Hainsworth R. et al .
A randomized, double-blind, placebo controlled phase III study in patients with metastatic
adenocarcinoma of the colon or rectum receiving first line chemotherapy with oxaliplatin/5-fluorouracil/leucovorin
and PTK787/ZK 222 584 or placebo (CONFIRM-1).
Proc Am Soc Clin Oncol.
2005;
24
3
- 40
Bismuth H, Adam R, Levi F. et al .
Resection of nonresectable liver metastasis from colorectal cancer after neoadjuvant
chemotherapy.
Ann Surg.
1996;
224
509-520
- 41
Giachetti B, Itzhaki M, Gruia G. et al .
Long-term survival of patients with unresectable colorectal cancer liver metastases
following infusional chemotherapy with 5-fluoruracil, leucovorin, oxaliplatin and
surgery.
Ann Oncol.
1999;
10
663-669
- 42
Tournigand C, Cervantes A, Figer A, et .
al. OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-go
fashion in advanced colorectal cancer - a GERCOR study.
J Clin Oncol.
2006;
24
394-400
Prof. Dr. Wolff Schmiegel
Medizinische Universitätsklinik
Knappschaftskrankenhaus Bochum · In der Schornau 23-25 · 44892 Bochum
Email: wolff.schmiegel@rub.de