Skip to main content

Advertisement

Springer Nature Link
Log in

Duloxetine improves oxaliplatin-induced neuropathy in patients with colorectal cancer: an open-label pilot study

  • Original Article
  • Published:
Supportive Care in Cancer Aims and scope Submit manuscript

Abstract

Background

This open-label pilot study is aimed to evaluate the efficacy and tolerability of the antidepressant duloxetine, which is effective for diabetic neuropathic pain, in the treatment of chronic oxaliplatin-induced peripheral neuropathy (OIPN).

Methods

We enrolled a total of 39 patients with stage III or IV colorectal cancer with chronic OIPN. They were treated with duloxetine by increasing the dose from 30 mg/day to 60 mg/day. Patients’ pain intensity was rated at baseline and 12 weeks after duloxetine administration. The severity of neuropathic pain was evaluated using the visual analog scale (VAS) score and the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3 (NCI-CTCAE v3.0).

Results

Nine patients (23.1%) discontinued duloxetine before the end of treatment because of adverse events. Of the remaining 30 patients, 19 patients (63.3%) had a VAS score improvement. Among them, nine (47.4%) showed a simultaneous grade improvement, and the other 10 patients (52.6%) had a stable grade according to NCI-CTCAE v3.0. Treatment with duloxetine did not impair renal or liver function and did not interfere with chemotherapy.

Conclusions

Duloxetine is feasible in treating chronic OIPN with tolerable toxicity at a daily dose of 60 mg/day.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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. Weitz J, Koch M, Debus J et al (2005) Colorectal cancer. Lancet 365:153–165

    Article  PubMed  Google Scholar 

  2. Meyerhardt JA, Mayer RJ (2005) Systemic therapy for colorectal cancer. N Engl J Med 352:476–487

    Article  PubMed  CAS  Google Scholar 

  3. Kim GP, Erlichman C (2007) Oxaliplatin in the treatment of colorectal cancer. Expert Opin Drug Metab Toxicol 3:281–294

    Article  PubMed  CAS  Google Scholar 

  4. de Gramont A, Figer A, Seymour M et al (2000) Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 18:2938–2947

    PubMed  Google Scholar 

  5. Andre T, Boni C, Mounedji-Boudiaf L et al (2004) Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 350:2343–2351

    Article  PubMed  CAS  Google Scholar 

  6. Cassidy J, Tabernero J, Twelves C et al (2004) XELOX (capecitabine plus oxaliplatin): active first-line therapy for patients with metastatic colorectal cancer. J Clin Oncol 22:2084–2091

    Article  PubMed  CAS  Google Scholar 

  7. Tournigand C, Cervantes A, Figer A et al (2006) 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 24:394–400

    Article  PubMed  CAS  Google Scholar 

  8. Wilson RH, Lehky T, Thomas RR et al (2002) Acute oxaliplatin-induced peripheral nerve hyperexcitability. J Clin Oncol 20:1767–1774

    Article  PubMed  CAS  Google Scholar 

  9. Extra JM, Marty M, Brienza S et al (1998) Pharmacokinetics and safety profile of oxaliplatin. Semin Oncol 25:13–22

    PubMed  CAS  Google Scholar 

  10. Grothey A (2003) Oxaliplatin-safety profile: neurotoxicity. Semin Oncol 30:5–13

    Article  PubMed  CAS  Google Scholar 

  11. Saif MW, Reardon J (2005) Management of oxaliplatin-induced peripheral neuropathy. Ther Clin Risk Manag 1:249–258

    PubMed  CAS  Google Scholar 

  12. Wolf S, Barton D, Kottschade L et al (2008) Chemotherapy-induced peripheral neuropathy: prevention and treatment strategies. Eur J Cancer 44:1507–1515

    Article  PubMed  CAS  Google Scholar 

  13. Cathomas R, Koberle D, Ruhstaller T et al (2010) Heated (37 degrees C) oxaliplatin infusion in combination with capecitabine for metastatic colorectal carcinoma: can it reduce neuropathy? Support Care Cancer 18:1263–1270

    Article  PubMed  Google Scholar 

  14. Detke MJ, Lu Y, Goldstein DJ et al (2002) Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial. J Clin Psychiatry 63:308–315

    Article  PubMed  CAS  Google Scholar 

  15. Goldstein DJ, Mallinckrodt C, Lu Y et al (2002) Duloxetine in the treatment of major depressive disorder: a double-blind clinical trial. J Clin Psychiatry 63:225–231

    Article  PubMed  CAS  Google Scholar 

  16. Goldstein DJ, Lu Y, Detke MJ et al (2004) Duloxetine in the treatment of depression: a double-blind placebo-controlled comparison with paroxetine. J Clin Psychopharmacol 24:389–399

    Article  PubMed  CAS  Google Scholar 

  17. Goldstein DJ, Lu Y, Detke MJ et al (2005) Duloxetine vs. placebo in patients with painful diabetic neuropathy. Pain 116:109–118

    Article  PubMed  CAS  Google Scholar 

  18. Wernicke JF, Pritchett YL, D’Souza DN et al (2006) A randomized controlled trial of duloxetine in diabetic peripheral neuropathic pain. Neurology 67:1411–1420

    Article  PubMed  CAS  Google Scholar 

  19. Raskin J, Pritchett YL, Wang F et al (2005) A double-blind, randomized multicenter trial comparing duloxetine with placebo in the management of diabetic peripheral neuropathic pain. Pain Med 6:346–356

    Article  PubMed  Google Scholar 

  20. Price DD, McGrath PA, Rafii A et al (1983) The validation of visual analogue scales as ratio scale measures for chronic and experimental pain. Pain 17:45–56

    Article  PubMed  CAS  Google Scholar 

  21. Aun C, Lam YM, Collett B (1986) Evaluation of the use of visual analogue scale in Chinese patients. Pain 25:215–221

    Article  PubMed  CAS  Google Scholar 

  22. Trotti A, Colevas AD, Setser A et al (2003) CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 13:176–181

    Article  PubMed  Google Scholar 

  23. Greene FL (2002) The American Joint Committee on Cancer: updating the strategies in cancer staging. Bull Am Coll Surg 87:13–15

    PubMed  Google Scholar 

  24. Metzger U (1990) Adjuvant therapy for colon and rectal cancer. NIH Consensus Development Conference. Eur J Cancer 26:753–755

    Article  PubMed  CAS  Google Scholar 

  25. Benson AB 3rd, Schrag D, Somerfield MR et al (2004) American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol 22:3408–3419

    Article  PubMed  Google Scholar 

  26. Kuebler JP, Wieand HS, O’Connell MJ et al (2007) Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol 25:2198–2204

    Article  PubMed  CAS  Google Scholar 

  27. Tesfaye S (2009) Advances in the management of diabetic peripheral neuropathy. Curr Opin Support Palliat Care 3:136–143

    Article  PubMed  Google Scholar 

  28. Grolleau F, Gamelin L, Boisdron-Celle M et al (2001) A possible explanation for a neurotoxic effect of the anticancer agent oxaliplatin on neuronal voltage-gated sodium channels. J Neurophysiol 85:2293–2297

    PubMed  CAS  Google Scholar 

  29. Ta LE, Espeset L, Podratz J et al (2006) Neurotoxicity of oxaliplatin and cisplatin for dorsal root ganglion neurons correlates with platinum-DNA binding. Neurotoxicology 27:992–1002

    Article  PubMed  CAS  Google Scholar 

  30. Schmeichel AM, Schmelzer JD, Low PA (2003) Oxidative injury and apoptosis of dorsal root ganglion neurons in chronic experimental diabetic neuropathy. Diabetes 52:165–171

    Article  PubMed  CAS  Google Scholar 

  31. Willis WD, Coggeshall RE (1991) Sensory mechanisms of the spinal cord. Plenum, New York

    Google Scholar 

  32. Basbaum AI, Fields HL (1984) Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry. Annu Rev Neurosci 7:309–338

    Article  PubMed  CAS  Google Scholar 

  33. Suzuki R, Rygh LJ, Dickenson AH (2004) Bad news from the brain: descending 5-HT pathways that control spinal pain processing. Trends Pharmacol Sci 25:613–617

    Article  PubMed  CAS  Google Scholar 

  34. Coderre TJ, Katz J (1997) Peripheral and central hyperexcitability: differential signs and symptoms in persistent pain. Behav Brain Sci 20:404–419, discussion 435–513

    PubMed  CAS  Google Scholar 

  35. Ren K, Dubner R (2002) Descending modulation in persistent pain: an update. Pain 100:1–6

    Article  PubMed  Google Scholar 

  36. Iyengar S, Webster AA, Hemrick-Luecke SK et al (2004) Efficacy of duloxetine, a potent and balanced serotonin-norepinephrine reuptake inhibitor in persistent pain models in rats. J Pharmacol Exp Ther 311:576–584

    Article  PubMed  CAS  Google Scholar 

  37. Stahl SM, Grady MM, Moret C et al (2005) SNRIs: their pharmacology, clinical efficacy, and tolerability in comparison with other classes of antidepressants. CNS Spectr 10:732–747

    PubMed  Google Scholar 

  38. Rowbotham MC, Goli V, Kunz NR et al (2004) Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study. Pain 110:697–706

    Article  PubMed  CAS  Google Scholar 

  39. Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG et al (2001) Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology 25:871–880

    Article  PubMed  CAS  Google Scholar 

  40. Brannan SK, Mallinckrodt CH, Brown EB et al (2005) Duloxetine 60 mg once-daily in the treatment of painful physical symptoms in patients with major depressive disorder. J Psychiatr Res 39:43–53

    Article  PubMed  Google Scholar 

  41. Jin Y, Desta Z, Stearns V et al (2005) CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst 97:30–39

    Article  PubMed  CAS  Google Scholar 

  42. Bosch TM, Meijerman I, Beijnen JH et al (2006) Genetic polymorphisms of drug-metabolising enzymes and drug transporters in the chemotherapeutic treatment of cancer. Clin Pharmacokinet 45:253–285

    Article  PubMed  CAS  Google Scholar 

  43. Hewes JC, Riddy D, Morris RW et al (2006) A prospective study of isolated human hepatocyte function following liver resection for colorectal liver metastases: the effects of prior exposure to chemotherapy. J Hepatol 45:263–270

    Article  PubMed  CAS  Google Scholar 

  44. Masek V, Anzenbacherova E, Machova M et al (2009) Interaction of antitumor platinum complexes with human liver microsomal cytochromes P450. Anticancer Drugs 20:305–311

    Article  PubMed  CAS  Google Scholar 

  45. Hanioka N, Ozawa S, Jinno H et al (2002) Interaction of irinotecan (CPT-11) and its active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38) with human cytochrome P450 enzymes. Drug Metab Dispos 30:391–396

    Article  PubMed  CAS  Google Scholar 

  46. Park JY, Kim KA (2003) Inhibitory effect of 5-fluorouracil on human cytochrome P(450) isoforms in human liver microsomes. Eur J Clin Pharmacol 59:407–409

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported in part by grants from the Taiwan Clinical Oncology Research Foundation.

Disclosures

The authors declare no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Psychiatry, Taipei City Hospital Renai Branch, Taipei, Taiwan

    Ya-Hsu Yang

  2. Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan

    Jen-Kou Lin, Wei-Shone Chen, Tzu-Chen Lin, Shung-Haur Yang, Jeng-Kai Jiang, Shih-Ching Chang, Yuan-Tzu Lan & Chun-Chi Lin

  3. Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shi-Pai Road, Taipei, 112, Taiwan

    Chueh-Chuan Yen, Cheng-Hwai Tzeng, Chung-Jen Teng & Hao-Wei Teng

  4. Division of Hematology and Oncology, Department of Medicine, National Yang-Ming University Hospital, No. 152, Xin Min Road, Yilan, 26042, Taiwan

    Wei-Shu Wang & Chung-Jen Teng

  5. Department of Psychiatry, New Taipei City Hospital, Taipei, Taiwan

    Huey-Ling Chiang

  6. Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan

    Huey-Ling Chiang

  7. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan

    Hao-Wei Teng

  8. National Yang-Ming University School of Medicine, Taipei, Taiwan

    Ya-Hsu Yang, Jen-Kou Lin, Wei-Shone Chen, Tzu-Chen Lin, Shung-Haur Yang, Jeng-Kai Jiang, Shih-Ching Chang, Yuan-Tzu Lan, Chun-Chi Lin, Chueh-Chuan Yen, Cheng-Hwai Tzeng, Wei-Shu Wang, Chung-Jen Teng & Hao-Wei Teng

Authors
  1. Ya-Hsu Yang
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Jen-Kou Lin
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Wei-Shone Chen
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Tzu-Chen Lin
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Shung-Haur Yang
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Jeng-Kai Jiang
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Shih-Ching Chang
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Yuan-Tzu Lan
    View author publications

    You can also search for this author inPubMed Google Scholar

  9. Chun-Chi Lin
    View author publications

    You can also search for this author inPubMed Google Scholar

  10. Chueh-Chuan Yen
    View author publications

    You can also search for this author inPubMed Google Scholar

  11. Cheng-Hwai Tzeng
    View author publications

    You can also search for this author inPubMed Google Scholar

  12. Wei-Shu Wang
    View author publications

    You can also search for this author inPubMed Google Scholar

  13. Huey-Ling Chiang
    View author publications

    You can also search for this author inPubMed Google Scholar

  14. Chung-Jen Teng
    View author publications

    You can also search for this author inPubMed Google Scholar

  15. Hao-Wei Teng
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding authors

Correspondence to Chung-Jen Teng or Hao-Wei Teng.

Additional information

Chung-Jen Teng and Hao-Wei Teng have equal contribution.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yang, YH., Lin, JK., Chen, WS. et al. Duloxetine improves oxaliplatin-induced neuropathy in patients with colorectal cancer: an open-label pilot study. Support Care Cancer 20, 1491–1497 (2012). https://doi.org/10.1007/s00520-011-1237-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-011-1237-2

Keywords