Skip to main content

Advertisement

SpringerLink
Log in

Adjuvant chemotherapy with folinic acid and 5-fluorouracil in patients with locally advanced rectal cancer previously treated by preoperative radiochemotherapy and curative tumor resection

  • Original Article
  • Published:
International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Background and aims

The role of postoperative adjuvant chemotherapy in patients with rectal cancer pretreated by preoperative radiochemotherapy (RCT) and curative surgery is still poorly investigated.

Patients and methods

We pooled data from both arms of a phase III trial in which patients with locally advanced (T3/4) rectal cancer were randomized to preoperative RCT alone or combined with pelvic radio-frequency hyperthermia. After surgery, R0-resected patients were scheduled to adjuvant chemotherapy with four monthly courses of 50 mg folinic acid (FA) and gradually escalated 5-fluorouracil (5-FU, 350–500 mg/m2, days 1–5). Reasons preventing initiation of chemotherapy and treatment-related toxicities were evaluated. Patients’ characteristics and survival parameters were compared between the treated and untreated patient groups.

Results

Out of 93 patients, 73 (79%) started adjuvant chemotherapy, whereas 19 (21%) did not, mostly due to perioperative complications and refusal. Chemotherapy-related toxicities were mild to moderate in most cases, but—together with protracted postoperative complications—prevented the intended dose escalation of 5-FU in 71% of patients. Distant-failure-free (p=0.03) and overall survival (p=0.03) were improved in the chemotherapy group, although there was a negative selection of patients with unfavourable characteristics into the untreated patient group.

Interpretation/conclusion

Adjuvant chemotherapy using FA and 5-FU can be safely applied to the majority of patients with rectal cancer pretreated by RCT and surgery. Survival data are not suitable to allow far-reaching conclusions, but are in line with suggestions of a favourable effect of adjuvant chemotherapy in these patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Douglas HO Jr, Moertel CG, Mayer RJ, Thomas PR, Lindblad AS, Mittleman A, Stablein DM, Bruckner HW (1986) Survival after postoperative combination treatment of rectal cancer (letter). N Engl J Med 315:1294–1295

    Article  Google Scholar 

  2. GITSG (1985) Prolongation of the disease-free interval in surgically treated rectal carcinoma. Gastrointestinal Tumor Study Group. N Engl J Med 312:1465–1472

    Article  Google Scholar 

  3. Krook JE, Moertel CG, Gunderson LL, Wieand HS, Collins RT, Beart RW, Kubista TP, Poon MA, Meyers WC, Mailliard JA et al (1991) Effective surgical adjuvant therapy for high-risk rectal carcinoma (see comments). N Engl J Med 324:709–715

    Article  PubMed  CAS  Google Scholar 

  4. NIH (1990) NIH consensus conference. Adjuvant therapy for patients with colon and rectal cancer. JAMA 264:1444–1450

    Article  Google Scholar 

  5. Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ (2001) Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 345:638–646

    Article  PubMed  CAS  Google Scholar 

  6. Kockerling F, Reymond MA, Altendorf-Hofmann A, Dworak O, Hohenberger W (1998) Influence of surgery on metachronous distant metastases and survival in rectal cancer. J Clin Oncol 16:324–329

    PubMed  CAS  Google Scholar 

  7. O’Connell MJ, Martenson JA, Wieand HS, Krook JE, Macdonald JS, Haller DG, Mayer RJ, Gunderson LL, Rich TA (1994) Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med 331:502–507

    Article  PubMed  CAS  Google Scholar 

  8. Swedish Rectal Cancer Trial (1997) Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med 336:980–987

    Article  Google Scholar 

  9. Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T et al (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731–1740

    Article  PubMed  CAS  Google Scholar 

  10. Hyams DM, Mamounas EP, Petrelli N, Rockette H, Jones J, Wieand HS, Deutsch M, Wickerham L, Fisher B, Wolmark N (1997) A clinical trial to evaluate the worth of preoperative multimodality therapy in patients with operable carcinoma of the rectum: a progress report of National Surgical Breast and Bowel Project Protocol R-03. Dis Colon Rectum 40:131–139

    Article  PubMed  CAS  Google Scholar 

  11. Minsky BD (1999) Primary treatment of rectal cancer: present and future. Crit Rev Oncol Hematol 32:19–30

    Article  PubMed  CAS  Google Scholar 

  12. Minsky BD, Cohen AM, Kemeny N, Enker WE, Kelsen DP, Reichman B, Saltz L, Sigurdson ER, Frankel J (1992) Enhancement of radiation-induced downstaging of rectal cancer by fluorouracil and high-dose leucovorin chemotherapy. J Clin Oncol 10:79–84

    PubMed  CAS  Google Scholar 

  13. Minsky BD, Cohen AM, Kemeny N, Enker WE, Kelsen DP, Saltz L, Frankel J (1993) The efficacy of preoperative 5-fluorouracil, high-dose leucovorin, and sequential radiation therapy for unresectable rectal cancer. Cancer 71:3486–3492

    Article  PubMed  CAS  Google Scholar 

  14. Minsky B, Cohen A, Enker W, Kelsen D, Kemeny N, Ilson D, Guillem J, Saltz L, Frankel J, Conti J (1994) Preoperative 5-fluorouracil, low-dose leucovorin, and concurrent radiation therapy for rectal cancer. Cancer 73:273–280

    Article  PubMed  CAS  Google Scholar 

  15. Rau B, Wust P, Hohenberger P, Loffel J, Hunerbein M, Below C, Gellermann J, Speidel A, Vogl T, Riess H, Felix R, Schlag PM (1998) Preoperative hyperthermia combined with radiochemotherapy in locally advanced rectal cancer: a phase II clinical trial. Ann Surg 227:380–389

    Article  PubMed  CAS  Google Scholar 

  16. Riess H, Loffel J, Wust P, Rau B, Gremmler M, Speidel A, Schlag P (1995) A pilot study of a new therapeutic approach in the treatment of locally advanced stages of rectal cancer: neoadjuvant radiation, chemotherapy and regional hyperthermia. Eur J Cancer 31A:1356–1360

    Article  PubMed  CAS  Google Scholar 

  17. Hildebrandt B, Wust P, Rau B, Schlag PM, Riess H (2000) Regional hyperthermia in rectal cancer. Lancet 356:771–772

    Article  PubMed  CAS  Google Scholar 

  18. Wust P, Hildebrandt B, Sreenivasa G, Rau B, Gellermann J, Riess H, Felix R, Schlag PM (2002) Hyperthermia in combined treatment of cancer. Lancet Oncol 3:487–497

    Article  PubMed  CAS  Google Scholar 

  19. Grann A, Feng C, Wong D, Saltz L, Paty PP, Guillem JG, Cohen AM, Minsky BD (2001) Preoperative combined modality therapy for clinically resectable uT3 rectal adenocarcinoma. Int J Radiat Oncol Biol Phys 49:987–995

    Article  PubMed  CAS  Google Scholar 

  20. Chan AK, Wong AO, Langevin J, Jenken D, Heine J, Buie D, Johnson DR (2000) Preoperative chemotherapy and pelvic radiation for tethered or fixed rectal cancer: a phase II dose escalation study. Int J Radiat Oncol Biol Phys 48:843–856

    PubMed  CAS  Google Scholar 

  21. Porschen R, Bermann A, Loffler T, Haack G, Rettig K, Anger Y, Strohmeyer G (2001) Fluorouracil plus leucovorin as effective adjuvant chemotherapy in curatively resected stage III colon cancer: results of the trial adjCCA-01. J Clin Oncol 19:1787–1794

    PubMed  CAS  Google Scholar 

  22. Ahn JB, Shim KY, Jeung HC, Rha SY, Yoo NC, Kim NK, Roh JK, Min JS, Kim BS, Chung HC (2001) Monthly 5-days 5-fluorouracil and low-dose leucovorin for adjuvant chemotherapy in colon cancer. Cancer Lett 167:215–224

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grants of the German Research Ministry (DFG-SFB 273, GraKo 331).

Author information

Authors and Affiliations

  1. Medizinische Klinik für Hämatologie und Onkologie, Charité, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany

    Bert Hildebrandt, Jürgen Löffel, Annett Nicolaou, Philipp Le Coutre, Bernd Dörken & Hanno Riess

  2. Klinik für Chirurgie und Chirurgische Onkologie, Charité, Campus Berlin-Buch, Lindenberger Weg 80, 13125, Berlin, Germany

    Beate Rau

  3. Klinik für Strahlenheilkunde, Charité, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany

    Peter Wust, Johanna Gellermann & Roland Felix

  4. Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Charité, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany

    Peter Neuhaus

  5. Institut für Medizinische Biometrie, Charité, Campus Mitte, Luisenstrasse 65, 10117, Berlin, Germany

    Klaus-Dieter Wernecke

  6. Medizinische Klinik für Hämatologie und Onkologie Charite, Campus Virchow Klinikum, D-13344, Berlin, Germany

    Bert Hildebrandt

Authors
  1. Bert Hildebrandt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Beate Rau
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jürgen Löffel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peter Wust
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Annett Nicolaou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Johanna Gellermann
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Philipp Le Coutre
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Peter Neuhaus
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Roland Felix
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Klaus-Dieter Wernecke
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Bernd Dörken
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Hanno Riess
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bert Hildebrandt.

Additional information

We dedicate this manuscript to Dr. Jürgen Löffel, who unexpectedly died on December 16, 2003, at the age of 40. Dr. Löffel was an outstanding physician and oncologist. He significantly contributed to the planning, initiation and success of this study

B. Hildebrandt and B. Rau contributed equally to this manuscript

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hildebrandt, B., Rau, B., Löffel, J. et al. Adjuvant chemotherapy with folinic acid and 5-fluorouracil in patients with locally advanced rectal cancer previously treated by preoperative radiochemotherapy and curative tumor resection. Int J Colorectal Dis 21, 582–589 (2006). https://doi.org/10.1007/s00384-005-0054-9

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00384-005-0054-9

Keywords

Search

Navigation