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Off-label use of anti-cancer drugs between clinical practice and research: the Italian experience

European Journal of Clinical Pharmacology volume 68, pages 505–512 (2012)Cite this article

Abstract

Background

Off-label use is the practice of prescribing a drug outside the terms of its official labeling. Worldwide, about 20% of the commonly prescribed medications are off-label, and the percentage increases in specific patient populations, such as children, pregnant women, and cancer patients. Off-label use is particularly widespread in oncology for many reasons, including the wide variety of cancer subtypes, the difficulties involved in performing clinical trials, the rapid diffusion of preliminary results, and delays in the approval of new drugs by regulatory organizations/agencies.

Objective

The aim of this article is to describe the use of off-label drugs in oncology, with an emphasis on the role of the world’s leading regulatory agencies and an assessment of current Italian legislation.

Conclusion

Off-label drug utilization is essential in oncology when based on evidence. However, off-label drugs must be prescribed in accordance with existing national laws and only when the potential benefit outweighs the potential toxic effects.

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References

  1. Randall S, Stafford MD (2008) Regulating off-label drug use– rethinking the role of the FDA. N Engl J Med 358:1427–1429

    Article  Google Scholar 

  2. De Souza JA (2011) Off-label drug utilization in oncology. Clin Adv Hematol Oncol 9:473–475

    PubMed  Google Scholar 

  3. Conroy S, Newman C, Gudka S (2003) Unlicensed and off label drug use in acute lymphoblastic leukaemia and other malignancies in children. Ann Oncol 14:42–47

    PubMed  Article  CAS  Google Scholar 

  4. Brosgart CL, Mitchell T, Charlebois E et al (1996) Off-label drug use in human immunodeficiency virus disease. J Acquir Immune Defic Syndr Hum Retrovirol 12:56–62

    PubMed  Article  CAS  Google Scholar 

  5. Choonara I, Conroy S (2002) Unlicensed and off-label drug use in children: implications for safety. Drug Saf 25:1–5

    PubMed  Article  Google Scholar 

  6. Rayburn WF, Turnbull GL (1995) Off-label drug prescribing on a state university obstetric service. J Reprod Med 40:186–188

    PubMed  CAS  Google Scholar 

  7. Stone KJ, Viera AJ, Parman CL (2003) Off-label applications for SSRIs. Am Fam Physician 68:498–504

    PubMed  Google Scholar 

  8. Mortenson LE (1991) The off-label debate: a threat to the future of cancer care. Cancer Investig 9:597–599

    Article  CAS  Google Scholar 

  9. The American Cancer Society: Off-label drug use. Available at: http://www.cancer.org/Treatment/TreatmentsandSideEffects/TreatmentTypes/Chemotherapy/off-label-drug-use. (Last Medical Review: March 14, 2011)

  10. Levêque D, Michallat AC, Schaller C, Ranc M (2005) Off label drug use in adult patients treated by anticancer chemotherapy. Bull Cancer 92:498–500

    PubMed  Google Scholar 

  11. Poole SG, Dooley MJ (2004) Off-label prescribing in oncology. Support Care Cancer 12:302–305

    PubMed  Article  Google Scholar 

  12. Dean-Colombo W, Fang S, Smith W et al (2009) Off-label drug use in women with breast cancer. J Clin Oncol 27[15 suppl]:abstract 1016

  13. Kocs D, Fendrick AM (2003) Effect of off-label use of oncology drugs on pharmaceutical costs: the rituximab experience. Am J Manag Care 9:393–400

    PubMed  Google Scholar 

  14. Roila F, Ballatori E, Labianca R et al (2009) Off-label prescription of antineoplastic drugs: an Italian prospective, observational, multi center survey. Tumori 95:647–651

    PubMed  Google Scholar 

  15. Updated priority list for studies into off-patent pediatric medicinal products. European Medicines Agency: EMA/480197/2010. Available at:http://www.ema.europa.eu/docs/en_GB/library/Other/2009/10/WC500004017.pdf. Accessed 15 Sept 2011

  16. Trotta F, Leufkens HGM, Schellens JHM et al (2011) Evaluation of oncology drugs at the European medicines agengy and US food and drug administration: when differences have an impact on clinical practice. J Clin Oncol 29:2266–2272

    PubMed  Article  Google Scholar 

  17. Drummond M, Mason A (2009) Rationing new medicines in the UK. Br Med J 338:a3182

    Article  Google Scholar 

  18. Mason A, Drummond M, Ramsey S et al (2010) Comparison of anticancer drug coverage decisions in the United States and United Kingdom: does the evidence support the rhetoric? J Clin Oncol 28:3234–3238

    PubMed  Article  Google Scholar 

  19. Mason AR, Drummond MF (2009) Public funding of new cancer drugs: is NICE getting nastier? Eur J Cancer 45:1188–1192

    PubMed  Article  Google Scholar 

  20. Duran-Garcia E, Santos-Ramos B, Puigventos-Latorre F, Ortega (2011) A role of the hospital pharmacy and therapeutics committee in detecting and regulating off-label drug use, reply to letter. Int J Clin Pharm [Epub ahead of print]

  21. Assises de médicament Groupe 3 “Encadrer les prescriptions hors AMM” (2011). Dispositifs dérogatoires de prescription “hors AMM”. Available at: http://www.sante.gouv.fr/IMG/pdf/Dispositifs_derogatoires_de_prescription_hors_AMM_.pdf. Accessed 15 Sept 2011

  22. Agenzia Italiana del Farmaco (2007) Registro Farmaci Oncologici sottoposti a monitoraggio, Rapporto 2007. Available at http://antineoplastici.agenziafarmaco.it/Registro_farmaci.pdf. Accessed 15 Sept 2011

  23. American Society of Clinical Oncology (2006) Reimbursement for cancer treatment: coverage of off-label drug indications. J Clin Oncol 24:3206–3208

    Article  Google Scholar 

  24. Levêque D (2008) Off-label use of anticancer drugs. Lancet Oncol 9:1102–1107

    PubMed  Article  Google Scholar 

  25. Bach PB (2009) Limits on Medicare’s ability to control rising spending on cancer drugs. N Engl J Med 360:626–633

    PubMed  Article  CAS  Google Scholar 

  26. Mullins CD, Montgomery R, Tunis R (2010) Uncertainty in assessing value of oncology treatments. Oncologist 15:58–64

    PubMed  Article  Google Scholar 

  27. Weißbach L, Riese J (2006) Off-label use in oncology: an inexhaustible topic? Urologe A 45(11):1410–1414

    PubMed  Article  Google Scholar 

  28. Baldwin J (2002) Demand grows for early access to promising cancer drugs. J Natl Cancer Inst 94:1668–1670

    PubMed  Article  Google Scholar 

  29. Romond EH, Perez EA, Bryan J, Suman VJ et al (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2 positive breast cancer. N Engl J Med 353:1673–1684

    PubMed  Article  CAS  Google Scholar 

  30. Piccart-Gebhart MJ, Procter M, Leyland-Jones B et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353:1659–1672

    PubMed  Article  CAS  Google Scholar 

  31. Miller K, Wang M, Gralow J et al (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357:2666–2676

    PubMed  Article  CAS  Google Scholar 

  32. Kramer BS, Hagerty KL, Justman S et al (2009) Use of 5-α-Reductase inhibitors for prostate cancer chemoprevention: American Society of clinical Oncology/American Urological association 2008 clinical practice guideline. J Clin Oncol 27:1502–1516

    PubMed  Article  CAS  Google Scholar 

  33. Andriole GL, Bostwick D, Brawley OW et al (2010) Effect of dutasteride on the risk of prostate cancer. N Engl J Med 362:1192–1202

    PubMed  Article  CAS  Google Scholar 

  34. Casali PG (2007) The off-label use of drugs in oncology: a position paper by the European Society for Medical Oncology (ESMO). Ann Oncol 18:1923–1925

    PubMed  Article  CAS  Google Scholar 

  35. Gazarian M, Kelly M, McPhee JR et al (2006) Off-label use of medicines: consensus recommendations for evaluating appropriateness. Med J Aust 185:544–548

    PubMed  Google Scholar 

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Author information

Affiliations

  1. Hospital Pharmacy, I.R.C.C.S. Centro di Riferimento Oncologico di Basilicata, Via Padre Pio 1, 85028, Rionero in Vulture, PZ, Italy

    Rosa Lerose & Carla Papa

  2. Department of Onco-Hematology, I.R.C.C.S. Centro di Riferimento Oncologico di Basilicata, Rionero in Vulture, PZ, Italy

    Pellegrino Musto, Michele Aieta & Alfredo Tartarone

Authors
  1. Rosa Lerose
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  2. Pellegrino Musto
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  3. Michele Aieta
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  4. Carla Papa
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  5. Alfredo Tartarone
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Correspondence to Rosa Lerose.

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Lerose, R., Musto, P., Aieta, M. et al. Off-label use of anti-cancer drugs between clinical practice and research: the Italian experience. Eur J Clin Pharmacol 68, 505–512 (2012). https://doi.org/10.1007/s00228-011-1173-6

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  • DOI: https://doi.org/10.1007/s00228-011-1173-6

Keywords

  • Off-label
  • Regulatory agencies
  • Anti-cancer drugs