Skip to main content

Advertisement

Log in

Enhanced skin toxicity associated with the combination of clofarabine plus cytarabine for the treatment of acute leukemia

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

Abstract

Purpose

Skin toxicity is associated with a number of different chemotherapeutic agents used to treat acute leukemias. The term “toxic erythema of chemotherapy” (TEC) has been coined to describe a spectrum of skin findings, ranging from palmar–plantar erythrodysesthesia to erythema of major body folds, with erythroderma representing its most severe form. To clarify the types and frequencies of cutaneous reactions associated with clofarabine plus cytarabine chemotherapy and to compare these to those observed with clofarabine alone, we reviewed our institutional experience over a 5-year period.

Methods

We reviewed the medical records of 49 patients who were treated with either regimen for acute leukemia. To facilitate comparison of the cutaneous toxicities, only patients treated with clofarabine 40 mg/m2 daily for 5 days (days 1–5) with or without cytarabine 1 g/m2 daily for 5 days (days 2–6) were included.

Results

Ten patients were treated with clofarabine alone, and 40 patients received clofarabine plus cytarabine; one patient received both regimens. Treatment-associated skin toxicity developed 3–9 days following the initiation of chemotherapy and was more common in the group receiving the two-drug combination as compared to those receiving clofarabine alone [22/40 (55 %) vs. 1/10 (10 %) respectively, p = 0.014]. The majority of chemotherapy-related cutaneous side effects represented TEC.

Conclusions

Cutaneous toxicity was common and more frequent in the clofarabine plus cytarabine group when compared to patients treated with clofarabine alone. This finding is relevant for both clinicians and patients.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Bolognia JL, Cooper DL, Glusac EJ (2008) Toxic erythema of chemotherapy: a useful clinical term. J Am Acad Dermatol 59:524–529

    Article  PubMed  Google Scholar 

  2. Lipworth AD, Robert C, Zhu AX (2009) Hand–foot syndrome (hand–foot skin reaction, palmar–plantar erythrodysesthesia): focus on sorafenib and sunitinib. Oncology 77:257–271

    Article  CAS  PubMed  Google Scholar 

  3. Lokich JJ, Moore C (1984) Chemotherapy-associated palmar–plantar erythrodysesthesia syndrome. Ann Intern Med 101:798–799

    Article  CAS  PubMed  Google Scholar 

  4. Graves T, Hooks MA (1989) Drug-induced toxicities associated with high-dose cytosine arabinoside infusions. Pharmacotherapy 9:23–28

    CAS  PubMed  Google Scholar 

  5. Montillo M, Mirto S, Petti MC et al (1998) Fludarabine, cytarabine, and G-CSF (FLAG) for the treatment of poor risk acute myeloid leukemia. Am J Hematol 58:105–109

    Article  CAS  PubMed  Google Scholar 

  6. Kern W, Aul C, Maschmeyer G et al (1998) Superiority of high-dose over intermediate-dose cytosine arabinoside in the treatment of patients with high-risk acute myeloid leukemia: results of an age-adjusted prospective randomized comparison. Leukemia 12:1049–1055

    Article  CAS  PubMed  Google Scholar 

  7. Herzig RH, Wolff SN, Lazarus HM et al (1983) High-dose cytosine arabinoside therapy for refractory leukemia. Blood 62:361–369

    CAS  PubMed  Google Scholar 

  8. Faderl S, Gandhi V, O’Brien S et al (2005) Results of a phase 1-2 study of clofarabine in combination with cytarabine (ara-C) in relapsed and refractory acute leukemias. Blood 105:940–947

    Article  CAS  PubMed  Google Scholar 

  9. National cancer institute (2009) Common terminology criteria for adverse events v4.0. National cancer institute common terminology criteria for adverse events v40 NIH publication #09-7473: NCI, NIH, DHHS

  10. Buchholz S, Dammann E, Stadler M et al (2012) Cytoreductive treatment with clofarabine/ara-C combined with reduced-intensity conditioning and allogeneic stem cell transplantation in patients with high-risk, relapsed, or refractory acute myeloid leukemia and advanced myelodysplastic syndrome. Eur J Haematol 88:52–60

    Article  CAS  PubMed  Google Scholar 

  11. Hwang YY, Trendell-Smith NJ, Yeung CK et al (2012) Fatal palmar–plantar erythrodysesthesia after clofarabine and cytarabine chemotherapy. Acta Haematol 128:151–153

    Article  PubMed  Google Scholar 

  12. von Moos R, Thuerlimann BJ, Aapro M et al (2008) Pegylated liposomal doxorubicin-associated hand–foot syndrome: recommendations of an international panel of experts. Eur J Cancer 44:781–790

    Article  Google Scholar 

  13. Kang YK, Lee SS, Yoon DH et al (2010) Pyridoxine is not effective to prevent hand–foot syndrome associated with capecitabine therapy: results of a randomized, double-blind, placebo-controlled study. J Clin Oncol 28:3824–3829

    Article  CAS  PubMed  Google Scholar 

  14. von Gruenigen V, Frasure H, Fusco N et al (2010) A double-blind, randomized trial of pyridoxine versus placebo for the prevention of pegylated liposomal doxorubicin-related hand-foot syndrome in gynecologic oncology patients. Cancer 116:4735–4743

    Article  Google Scholar 

Download references

Acknowledgments

We thank Katherine Mandock, PharmD, for providing the pharmacy data.

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nikolai Podoltsev.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, B., Bolognia, J., Marks, P. et al. Enhanced skin toxicity associated with the combination of clofarabine plus cytarabine for the treatment of acute leukemia. Cancer Chemother Pharmacol 74, 303–307 (2014). https://doi.org/10.1007/s00280-014-2504-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-014-2504-y

Keywords

Navigation