Advertisement

The effect of COX-2 inhibitor on capecitabine-induced hand–foot syndrome in patients with stage II/III colorectal cancer: a phase II randomized prospective study

  • Rong-Xin Zhang
  • Xiao-Jun Wu
  • Shi-Xun Lu
  • Zhi-Zhong Pan
  • De-Sen Wan
  • Gong ChenEmail author
Original Paper

Abstract

Purpose

Hand–foot syndrome (HFS) is a common adverse event that can be induced by capecitabine. It is hypothesized that capecitabine (Hoffmann-La Roche Inc.) based chemotherapy can cause overexpression of COX-2 in tumor and healthy tissue, which finally induced HFS in hands and feet. Based on this, we believed that a selected COX-2 inhibitor (celecoxib, Pfizer Pharmaceuticals LLC) could ease HFS. We designed a prospective clinical study to test the hypothesis.

Methods

From August 2008 to January 2010, 110 patients with stage II/III colorectal cancer who were eligible for adjuvant chemotherapy were enrolled in the study and divided into 4 groups by random, but 9 patients did not finish at least 4 cycles of chemotherapy. There were sixteen patients in capecitabine group, and fifteen patients in capecitabine and celecoxib group. Thirty-four patients were in XELOX (capecitabine plus oxaliplatine) group, and thirty-six patients in XELOX+ celecoxib group. All 101 patients finished chemotherapy and follow-up interviews.

Results

The group that had received capecitabine and celecoxib had a significantly reduced frequency of  >grade 1 hand–foot syndrome (29 vs. 72% P < 0.001), and >grade 2 (11.76% vs. 30% P = 0.024). Five patients experienced grade 3 HFS in capecitabine group and only 1 patient had grade 3 HFS in capecitabine and celecoxib group. There were 5 patients in capecitabine group who refused to go on chemotherapy because of HFS, but there was none in capecitabine and celecoxib group.

Conclusions

From the result of this study, we could learn that celecoxib could reduce HFS that was induced by capecitabine. So we recommend that celecoxib can be used in capecitabine-based chemotherapy.

Keywords

Hand–foot syndrome Capecitabine Celecoxib Colorectal cancer Adjuvant chemotherapy Adverse event 

Notes

Acknowledgments

We are very thankful to Zhi-heng Peng and Zi-yi Huang for the acquisition of data.

Conflict of interest

We declare that there is no conflict of interest in this study.

References

  1. Baack BR, Burgdorf WH (1991) Chemotherapy-induced acral erythema. J Am Acad Dermatol 24:457–461PubMedCrossRefGoogle Scholar
  2. Cassidy J, Tabernero J, Twelves C et al (2004) XELOX (capecitabine plus oxaliplatin): active firstline therapy for patients with metastatic colorectal cancer. J Clin Oncol 22:2084–2091PubMedCrossRefGoogle Scholar
  3. Cianchi F, Cortesini C, Bechi P, Fantappiè O, Messerini L, Vannacci A, Sardi I, Baroni G, Boddi V, Mazzanti R, Masini E (2001) Up-regulation of cyclooxygenase 2 gene expression correlates with tumor angiogenesis in human colorectal cancer. Gastroenterology 121:1339–1347PubMedCrossRefGoogle Scholar
  4. Dong ZW, Qiao YL, Li LD, Chen YD, Wang RT, Lei TH et al (2002) Report of Chinese cancer control strategy. Chin Cancer 11:250–260Google Scholar
  5. Edward LIN, Jeffrey S, Morris et al (2002) Effect of celecoxib on capecitabine-induced hand-foot syndrome and antitumor activity. Oncology (Williston Park) 16:31–37Google Scholar
  6. Edward LIN, Steven A, Curley, Christopher C, Crane et al (2006) Retrospective study of capecitabine and celecoxib in metastatic colorectal cancer: potential benefits and COX-2 as the common mediator in pain, toxicities and survival? Am J Clin Oncol 29:232–239CrossRefGoogle Scholar
  7. Gill S, Loprinzi CL, Sargent DJ et al (2004) Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: who benefits and by how much? J Clin Oncol 22:1797–1806PubMedCrossRefGoogle Scholar
  8. Gressett SM, Stanford BL, Hardwicke F (2002) Management of hand-foot syndrome induced by capecitabine. J Oncol Pharm Pract 12:131–141CrossRefGoogle Scholar
  9. Gupta RA, DuBois RN (2001) Colorectal cancer prevention and treatment by inhibition of cyclooxygenase. Nat Rev Cancer 1:11–21PubMedCrossRefGoogle Scholar
  10. Howe LR, Dannenberg AJ (2002) A role for cyclooxygenase-2 inhibitors in the prevention and treatment of cancer. Semin Oncol 29:111–119PubMedGoogle Scholar
  11. Jemal A, Siegel R, Ward E et al (2008) Cancer statistics. CA Cancer J Clin 58:71–96PubMedCrossRefGoogle Scholar
  12. Moertel CG, Fleming TR, Macdonald JS et al (1990) Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. New Engl J Med 32:352–358CrossRefGoogle Scholar
  13. Nagore E, Insa A, Sanmartin O (2000) Antineoplastic therapy-induced palmar plantar erythrodysesthesia (‘hand-foot’) syndrome: incidence, recognition and management. Am J Clin Dermatol 1:225–234PubMedCrossRefGoogle Scholar
  14. Schmoll H-J, Cartwright T, Tabernero J et al (2007) Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1, 864 Patients. J Clin Oncol 25:102–108PubMedCrossRefGoogle Scholar
  15. Sheehan KM, Sheahan K, O’Donoghue DP, MacSweeney F, Conroy RM, Fitzgerald DJ, Murray FE (1999) The relationship between cyclooxygenase-2 expression and colorectal cancer. JAMA 282:1254–1257PubMedCrossRefGoogle Scholar
  16. Steinbach G, Lynch PM, Phillips RK, Wallace MH, Hawk E, Gordon GB, Wakabayashi N, Saunders B, Shen Y, Fujimura T, Su LK, Levin B (2000) The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 342:1946–1952PubMedCrossRefGoogle Scholar
  17. Twelves C, Wong A, Nowacki MP, Abt M, Burris H 3rd, Carrato A et al (2005) Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med 352:2696–2704PubMedCrossRefGoogle Scholar
  18. Yong J, Wei W, Ping L et al (2007) Controlled clinical research of Celecoxib In prophylaxising side effects caused by Capecitabine. Chinese J Composite Clinical Hygiene 9:6–8Google Scholar
  19. Zuehlke R (1974) Erythematous eruption of the palms and soles associated with mitotane therapy. Dermatologica 148:90–92PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Rong-Xin Zhang
    • 1
    • 2
  • Xiao-Jun Wu
    • 1
    • 2
  • Shi-Xun Lu
    • 1
    • 2
  • Zhi-Zhong Pan
    • 1
    • 2
  • De-Sen Wan
    • 1
    • 2
  • Gong Chen
    • 1
    • 2
    Email author
  1. 1.Department of Colorectal SurgeryCancer Center, Sun Yat-sen UniversityGuangzhouPeople’s Republic of China
  2. 2.State Key Laboratory of Oncology in South ChinaGuangzhouPeople’s Republic of China

Personalised recommendations