Skip to main content

Advertisement

SpringerLink
Log in

Preoperative radiotherapy with capecitabine and mitomycin C in locally advanced rectal carcinoma

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

To evaluate the efficacy and safety of preoperative radiotherapy with capecitabine and mitomycin C in patients with locally advanced rectal cancer.

Methods

A prospective, open-label, non-randomized, phase II study was performed on 49 patients with locally advanced rectal cancer. Preoperative radiotherapy was conducted on linear accelerators (15 or 18 MV) with a tumor dose of 45 Gy in 25 fractions over 5 weeks, combined with mitomycin C 7 mg/m2 on days 1 and 29 and oral capecitabine 825 mg/m2 twice daily on days 1–35. Surgery was performed 5–6 weeks after the end of chemoradiation. The primary study endpoint was histopathological complete regression rate (pCR; Dworak grade 4).

Results

Disease stage at diagnosis was T3 in 34 patients (69%) and T4 in 15 patients (31%). Positive lymph nodes were diagnosed in 28 patients (57%). Toxicity (all grades) was documented in 35 patients (71%). Grade 3 toxicities were radiation dermatitis (25%), diarrhea (2%), neutropenia (2%), and granulocytopenia (2%). No patient experienced grade 4 toxicity. A pCR was seen in 8 (16%, 95% CI 9–29%) patients, a major response was noted in 24 (49%) patients and a minor response in 14 (29%) patients. R0 resection was performed in 46 patients (93.9%) and R1 in 3 patients (6.1%). Histopathological tumor downstaging was documented in 26 patients (53%). One-year disease-free survival was 93.3% and 1-year survival was 97.7%.

Conclusion

Preoperative chemoradiation with capecitabine and mitomycin C appeared to be effective with low toxicity in patients with locally advanced rectal cancer.

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. Valentini V, Glimelius B, Minsky B, Van Cutsem E, Bartelink H, Beets-Tan RG, Gerard JP, Kosmidis P, Pahlman L, Picciocchi A, Quirke P, Tepper J, Tonato M, Van de Velde CJ, Cellini N, Latini P (2005) The multidisciplinary rectal cancer treatment: main convergences, controversial aspects and investigational areas which support the need for an European Consensus. Radiother Oncol 76:241–250

    Article  PubMed  Google Scholar 

  2. Bujko K, Nowacki MP (2002) Emerging standards of radiotherapy combined with radical rectal cancer surgery. Cancer Treat Rev 28:101–103

    Article  PubMed  CAS  Google Scholar 

  3. Bosset JF, Calais G, Daban A, Berger C, Radošević-Jelić LJ, Maingon P, Bardet E, Pierart M, Briffaux A, EORTC Radiotherapy Group (2004) Preoperative chemoradiotherapy versus preoperative radiotherapy in rectal cancer patients: assessment of acute-toxicity and treatment compliance. Report of the 22921 randomized trial conducted by the EORTC Radiotherapy Group. Eur J Cancer 40:219–224

    Article  PubMed  CAS  Google Scholar 

  4. Gérard JP, Conroy T, Bonnetain F, Bouché O, Chapet O, Closon-Dejardin MT, Untereiner M, Leduc B, Francois E, Maurel J, Seitz JF, Buecher B, Mackiewicz R, Ducreux M, Bedenne L (2006) Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol 24:4620–4625

    Article  PubMed  Google Scholar 

  5. Seiwert YT, Salama JK, Everett EV (2007) The concurrent chemoradiation paradigm—general principles. Nat Clin Pract Oncol 4:86–100

    Article  PubMed  CAS  Google Scholar 

  6. Blanquicett C, Gillespie GY, Nabors LB, Miller CR, Bharara S, Buchsbaum DJ, Diasio RB, Johnson MR (2002) Induction of thymidine phosphorylase in both irradiated and shielded, contralateral human U87MG glioma xenografts: implications for a dual modality treatment using capecitabine and irradiation. Mol Cancer Ther 1:1139–1145

    PubMed  CAS  Google Scholar 

  7. Sawada N, Ishikawa T, Sekiguchi F, Tanaka Y, Ishitsuka H (1999) X-ray irradiation induces thymidine phosphorylase and enhances the efficacy of capecitabine (Xeloda) in human cancer xenografts. Clin Cancer Res 5:2948–2953

    PubMed  CAS  Google Scholar 

  8. Colvin OM, Friedman HS (2005) Alkylating agents—mitomycin C. In: DeVita VT, Hellman S, Rosenberg SA (eds) Cancer principles and practice of oncology, 7th edn. Lippincot Williams and Wilkins, Philadelphia, pp 332–344

    Google Scholar 

  9. Ogata Y, Matono K, Sasatomi T, Ishibashi N, Torigoe S, Fukumitsu T, Mizobe T, Yamashita N, Yanagawa T, Shirouzu K (2006) Upregulation of thymidine phosphorylase in rectal cancer tissues by mitomycin C. J Surg Oncol 93:47–55

    Article  PubMed  CAS  Google Scholar 

  10. ICRU Report 50 (1993) Prescribing, recording and reporting photon beam therapy. International Commission on Radiation Units and Measurements, Washington

    Google Scholar 

  11. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 92:205–216

    Article  PubMed  CAS  Google Scholar 

  12. NCI-Common Toxicity Criteria (1999) Version 2.0. National Cancer Institute, Division of Cancer Treatment

  13. Dworak O, Keilholz L, Hoffmann A (1997) Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis 12:19–23

    Article  PubMed  CAS  Google Scholar 

  14. Medina PJ, Sipols JM, George JN (2001) Drug-associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Curr Opin Hematol 8:286–293

    Article  PubMed  CAS  Google Scholar 

  15. Valentini V, Coco C, Picciocchi A, Morganti A, Trodella L, Ciabattoni A, Cellini F, Barbaro B, Cogliandolo S, Nuzzo G, Doglietto GB, Ambesi-Impiombato F, Cosimelli M (2002) Does downstaging predict improved outcome after preoperative chemoradiation for extraperitoneal locally advanced rectal cancer? A long-term analysis of 165 patients. Int J Radiat Oncol Biol Phys 53:664–674

    Article  PubMed  Google Scholar 

  16. Chau I, Allen M, Cunningham D, Tait D, Brown G, Hill M, Sumpter K, Rhodes A, Wotherspoon A, Norman AR, Hill A, Massey A, Prior Y (2003) Neoadjuvant systemic fluorouracil and mitomycin C prior to synchronous chemoradiation is an effective strategy in locally advanced rectal cancer. Br J Cancer 88:1017–1024

    Article  PubMed  CAS  Google Scholar 

  17. Van Cutsem E, Twelves C, Cassidy J, Allman D, Bajetta E, Boyer M, Bugat R, Findlay M, Frings S, Jahn M, McKendrick J, Osterwalder B, Perez-Manga G, Rosso R, Rougier P, Schmiegel WH, Seitz JF, Thompson P, Vieitez JM, Weitzel C, Harper P, Xeloda Colorectal Cancer Study Group (2001) Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol 19:4097–4106

    PubMed  Google Scholar 

  18. Hoff PM, Ansari R, Batist G, Cox J, Kocha W, Kuperminc M, Maroun J, Walde D, Weaver C, Harrison E, Burger HU, Osterwalder B, Wong AO, Wong R (2001) Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol 19:2282–2292

    PubMed  CAS  Google Scholar 

  19. Twelves C, Wong A, Nowacki MP, Abt M, Burris H 3rd, Carrato A, Cassidy J, Cervantes A, Fagerberg J, Georgoulias V, Husseini F, Jodrell D, Koralewski P, Kröning H, Maroun J, Marschner N, McKendrick J, Pawlicki M, Rosso R, Schüller J, Seitz JF, Stabuc B, Tujakowski J, Van Hazel G, Zaluski J, Scheithauer W (2005) Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med 352:2696–2704

    Article  PubMed  CAS  Google Scholar 

  20. Twelves C, Boyer M, Findlay M, Cassidy J, Weitzel C, Barker C, Osterwalder B, Jamieson C, Hieke K, Xeloda Colorectal Cancer Study Group (2001) Capecitabine (Xeloda) improves medical resource use compared with 5-fluorouracil plus leucovorin in a phase III trial conducted in patients with advanced colorectal carcinoma. Eur J Cancer 37:597–604

    Article  PubMed  CAS  Google Scholar 

  21. Hofheinz R, Wenz F, Post S, Matzdorff A, Laechelt S, Mueller L, Link H, Moehler M, Burkholder I, Hochhaus A (2009) Capecitabine (Cape) versus 5-fluorouracil (5-FU)-based (neo-)adjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC): safety results of a randomized, phase III trial. J Clin Oncol 27:15s (suppl; abstr 4014)

    Google Scholar 

  22. Glynne-Jones R, Meadows H, Wan S, Gollins S, Leslie M, Levine E, McDonald AC, Myint S, Samuel L, Sebag-Montefiore D, National Cancer Research Institute Anal Sub Group and Colorectal Clinical Oncology Group (2008) EXTRA-a multicenter phase II study of chemoradiation using a 5 day per week oral regimen of capecitabine and intravenous mitomycin C in anal cancer. Int J Radiat Oncol Biol Phys 72:119–126

    Article  PubMed  CAS  Google Scholar 

  23. Glynne-Jones R, Dunst J, Sebag-Montefiore D (2006) The integration of oral capecitabine into chemoradiation regimens for locally advanced rectal cancer: how successful have we been? Ann Oncol 17:361–371

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant from the Ministry of Science and Environmental Protection of Serbia (Project No. 145059).

Author information

Authors and Affiliations

  1. Department of Radiotherapy, Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000, Belgrade, Serbia

    Suzana Stojanovic, Ljiljana Radosevic-Jelic & Nenad Borojevic

  2. Department of Medical Oncology, Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000, Belgrade, Serbia

    Ivan Popov & Vladimir Nikolic

  3. Department of Pathology, Institute for Gastrointestinal Diseases, University Clinical Centre, Pasterova 2, 11000, Belgrade, Serbia

    Marjan Micev

  4. Department of Surgery, Institute for Gastrointestinal Diseases, University Clinical Centre, Pasterova 2, 11000, Belgrade, Serbia

    Zoran Krivokapic & Dragutin Kecmanovic

  5. Institute for Oncology and Radiology of Serbia, Data Center, Pasterova 14, 11000, Belgrade, Serbia

    Dusica Gavrilovic & Iva Kezic

Authors
  1. Suzana Stojanovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ivan Popov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ljiljana Radosevic-Jelic
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marjan Micev
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nenad Borojevic
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vladimir Nikolic
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zoran Krivokapic
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Dragutin Kecmanovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dusica Gavrilovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Iva Kezic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Suzana Stojanovic.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stojanovic, S., Popov, I., Radosevic-Jelic, L. et al. Preoperative radiotherapy with capecitabine and mitomycin C in locally advanced rectal carcinoma. Cancer Chemother Pharmacol 68, 787–793 (2011). https://doi.org/10.1007/s00280-010-1469-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-010-1469-8

Keywords

Search

Navigation