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Strahlentherapie und Onkologie

, Volume 186, Issue 12, pp 658–664 | Cite as

Induction Chemotherapy before Chemoradiotherapy and Surgery for Locally Advanced Rectal Cancer

Is It Time for a Randomized Phase III Trial?
  • Claus RödelEmail author
  • Dirk Arnold
  • Heinz Becker
  • Rainer Fietkau
  • Michael Ghadimi
  • Ullrich Graeven
  • Clemens Hess
  • Ralf Hofheinz
  • Werner Hohenberger
  • Stefan Post
  • Rudolf Raab
  • Rolf Sauer
  • Frederick Wenz
  • Torsten Liersch
Review Article

Background:

In the era of preoperative chemoradiotherapy (CRT) and total mesorectal excision (TME), the development of distant metastases is the predominant mode of failure in rectal cancer patients today. Integrating more effective systemic therapy into combined modality programs is the challenge. The question that needs to be addressed is how and when to apply systemic treatment with adequate dose and intensity.

Material and Methods:

This review article focuses on phase II–III trials designed to improve 5-fluorouracil (5-FU)-based combined modality treatment for rectal cancer patients through the inclusion of concurrent, adjuvant or, most recently, induction combination chemotherapy. Computerized bibliographic searches of PubMed were supplemented with hand searches of reference lists and abstracts of ASCO/ASTRO/ESTRO meetings.

Results:

After preoperative CRT and surgical resection, approximately one third of patients do not receive adjuvant chemotherapy, mainly due to surgical complications, patients’ refusal, or investigator’s discretion. In order to be able to apply chemotherapy with sufficient dose and intensity, an innovative approach is to deliver systemic therapy prior to preoperative CRT rather than adjuvant chemotherapy. Emerging evidence from several phase II trials and, recently, randomized phase II trials indicate that induction chemotherapy is feasible, does not compromise CRT or surgical resection, and enables the delivery of chemotherapy in adequate dose and intensity. Although this approach did not increase local efficacy in recent trials (e.g., pathological complete response rates, tumor regression, R0 resection rates, local control), it may help to improve control of distant disease.

Conclusion:

Whether this improvement in applicability and dose density of chemotherapy will ultimately translate into improved disease-free survival will have to be tested in a larger phase III trial.

Key Words

Rectal cancer Induction chemotherapy Chemoradiotherapy 

Induktionschemotherapie vor Radiochemotherapie und Operation beim lokal fortgeschrittenen Rektumkarzinom: Zeit für eine randomisierte Phase-III-Studie?

Hintergrund:

Nach Einführung der präoperativen Radiochemotherapie (RCT) und der totalen mesoerektalen Excision manifestieren sich Rezidive beim Rektumkarzinom am häufigsten als Fernmetastasen. Daher ist die Integration einer systemisch effektiveren Therapie in das multimodale Behandlungskonzept derzeit die entscheidende Herausforderung. Die Frage ist, wann und wie diese Systemtherapie mit adäquater Dosis und Intensität verabreicht werden kann.

Material und Methoden:

Der Übersichtsartikel beschreibt Phase II–III Studien, deren Ziel es war, die allein 5-FU-basierte multimodale Behandlung durch Hinzunahme einer Kombinations-Chemotherapie, simultan zur Radiotherapie, adjuvant oder als Induktionstherapie, zu verbessern. Dazu diente eine Suchabfrage in Pubmed, in Referenzlisten publizierter Arbeiten sowie Abstrakts von ASCO/ASTRO/ESTRO-Konferenzen.

Ergebnisse:

Nach präoperativer RCT und Operation erhalten etwa ein Drittel aller Patienten wegen postoperativer Komplikationen, patientenseitiger Ablehnung oder Entscheidung des betreuenden Arztes keine adjuvante Chemotherapie. Ein innovativer Ansatz ist die Induktionschemotherapie vor präoperativer RCT und Operation, um die systemische Therapie in ausreichender Dosierung und Intensität durchführen zu können. Eine Vielzahl an Phase II-Studien, und zuletzt auch randomisierter Phase- II-Studien, zeigte, dass dieses Konzept durchführbar ist, die anschließende RCT und Operation nicht kompromittiert sowie die systemische Komponente in adäquater Dosis und Intensität applizierbar macht. Wenngleich dadurch die lokale Wirksamkeit (histopathologisch bestätigte Komplettremission, Tumorregression, R0-Resektionsrate, lokale Kontrolle) nicht verbessert wurde, könnte sich dieses Vorgehen positiv auf die systemische Tumorkontrolle auswirken.

Schlussfolgerung:

Eine Phase-III-Studie muss klären, ob die verbesserte Durchführbarkeit und Dosisdichte einer Induktionschemotherapie das krankheitsfreie Überleben verbessern kann.

Schlüsselwörter

Rektumkarzinom Induktionschemotherapie Radiochemotherapie 

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Copyright information

© Urban & Vogel, Muenchen 2010

Authors and Affiliations

  • Claus Rödel
    • 1
    • 12
    Email author
  • Dirk Arnold
    • 2
  • Heinz Becker
    • 3
  • Rainer Fietkau
    • 4
  • Michael Ghadimi
    • 3
  • Ullrich Graeven
    • 5
  • Clemens Hess
    • 6
  • Ralf Hofheinz
    • 7
  • Werner Hohenberger
    • 8
  • Stefan Post
    • 9
  • Rudolf Raab
    • 10
  • Rolf Sauer
    • 4
  • Frederick Wenz
    • 11
  • Torsten Liersch
    • 3
  1. 1.Klinik für Strahlentherapie und OnkologieUniversität FrankfurtFrankfurt am MainGermany
  2. 2.Klinik und Poliklinik für Innere Medizin IVUniversität HalleHalleGermany
  3. 3.Klinik für Allgemein- und VisceralchirurgieUniversität GöttingenGöttingenGermany
  4. 4.StrahlenklinikUniversität ErlangenErlangenGermany
  5. 5.Klinik für Hämatologie, Onkologie und GastroenterologieKliniken Maria Hilf GmbHMönchengladbachGermany
  6. 6.Klinik für Strahlentherapie und RadioonkologieUniversität GöttingenGöttingenGermany
  7. 7.III. Medizinischen Klinik Hämatologie und Internistische OnkologieUniversitätsmedizin MannheimMannheimGermany
  8. 8.Chirurgische KlinikUniversität ErlangenErlangenGermany
  9. 9.Chirurgische KlinikUniversitätsmedizin MannheimMannheimGermany
  10. 10.Klinik für Allgemein- und VisceralchirurgieKlinikum OldenburgOldenburgGermany
  11. 11.Klinik für Strahlentherapie und RadioonkologieUniversitätsmedizin MannheimMannheimGermany
  12. 12.Department of Radiotherapy and OncologyJohann Wolfgang Goethe University FrankfurtFrankfurt am MainGermany

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