Advertisement

Cancer Chemotherapy and Pharmacology

, Volume 84, Issue 1, pp 217–221 | Cite as

Development of cutaneous squamous cell carcinoma after prolonged exposure to pegylated liposomal doxorubicin and hand–foot syndrome: a newly recognized toxicity

  • Daniel F. Pease
  • Bruce A. Peterson
  • Scott Gilles
  • Maria K. Hordinsky
  • Kimberly A. Bohjanen
  • Keith M. SkubitzEmail author
Short Communication

Abstract

Pegylated liposomal doxorubicin (PLD) can be administered for prolonged periods with minimal toxicity. The risk of cutaneous squamous cell carcinoma (SCC) with this therapy has not been reported. We describe cutaneous SCC of the plantar foot in two patients exposed to high doses of PLD. A 50-year-old man with angiosarcoma received a total PLD dose of 1350 mg/m2 and developed cutaneous SCC of bilateral plantar feet. A 45-year-old woman with cutaneous T-cell lymphoma was treated with a total PLD dose of 1142 mg/m2 with subsequent diagnosis of cutaneous SCC of the right plantar foot. No risk factors for SCC of the plantar foot were identified in either patient. Cutaneous SCC is likely an unreported side effect of prolonged exposure to PLD. An extended duration of hand–foot syndrome from other anti-cancer drugs may also share this risk. Regular complete skin examination with early intervention for suspicious lesions is indicated in this patient population.

Keywords

Pegylated liposomal doxorubicin Doxorubicin Sarcoma Lymphoma Drug-related side effect 

Notes

Acknowledgements

We would like to thank Michael Franklin for providing copyediting assistance on this manuscript, and the Kevin Franklin and James Dinnerstein families for research support.

Funding

There are no funding sources to report related to this manuscript.

Compliance with ethical standards

Conflict of interest

The authors have no potential conflicts of interests to report.

References

  1. 1.
    Jacobi U, Waibler E, Schulze P, Sehouli J, Oskay-Ozcelik G, Schmook T, Sterry W, Lademann J (2005) Release of doxorubicin in sweat: first step to induce the palmar-plantar erythrodysesthesia syndrome? Ann Oncol 16(7):1210–1211CrossRefGoogle Scholar
  2. 2.
    Lotem M, Hubert A, Lyass O, Goldenhersh MA, Ingber A, Peretz T, Gabizon A (2000) Skin toxic effects of polyethylene glycol-coated liposomal doxorubicin. Arch Dermatol 136(12):1475–1480CrossRefGoogle Scholar
  3. 3.
    Harbeck N, Saupe S, Jager E, Schmidt M, Kreienberg R, Muller L, Otremba BJ, Waldenmaier D, Dorn J, Warm M et al (2017) A randomized phase III study evaluating pegylated liposomal doxorubicin versus capecitabine as first-line therapy for metastatic breast cancer: results of the PELICAN study. Breast Cancer Res Treat 161(1):63–72CrossRefGoogle Scholar
  4. 4.
    Skubitz KM (2003) Phase II trial of pegylated-liposomal doxorubicin (Doxil) in sarcoma. Cancer Invest 21(2):167–176CrossRefGoogle Scholar
  5. 5.
    Staropoli N, Ciliberto D, Botta C, Fiorillo L, Grimaldi A, Lama S, Caraglia M, Salvino A, Tassone P, Tagliaferri P (2014) Pegylated liposomal doxorubicin in the management of ovarian cancer: a systematic review and metaanalysis of randomized trials. Cancer Biol Ther 15(6):707–720CrossRefGoogle Scholar
  6. 6.
    Gabizon A, Dagan A, Goren D, Barenholz Y, Fuks Z (1982) Liposomes as in vivo carriers of adriamycin: reduced cardiac uptake and preserved antitumor activity in mice. Can Res 42(11):4734–4739Google Scholar
  7. 7.
    Skubitz KM, Blaes AH, Konety SH, Francis GS (2017) Cardiac safety profile of patients receiving high cumulative doses of pegylated-liposomal doxorubicin: use of left ventricular ejection fraction is of unproven value. Cancer Chemother Pharmacol 80(4):787–798CrossRefGoogle Scholar
  8. 8.
    Breaker K, Naam M, La Rosa FG, Flaig IP, Flaig TW (2013) Skin cancer associated with the use of sorafenib and sunitinib for renal cell carcinoma. Dermatol Surg 39(7):981–987CrossRefGoogle Scholar
  9. 9.
    Dubauskas Z, Kunishige J, Prieto VG, Jonasch E, Hwu P, Tannir NM (2009) Cutaneous squamous cell carcinoma and inflammation of actinic keratoses associated with sorafenib. Clin Genitourin Cancer 7(1):20–23CrossRefGoogle Scholar
  10. 10.
    Lacouture ME, Desai A, Soltani K, Petronic-Rosic V, Laumann AE, Ratain MJ, Stadler WM (2006) Inflammation of actinic keratoses subsequent to therapy with sorafenib, a multitargeted tyrosine-kinase inhibitor. Clin Exp Dermatol 31(6):783–785CrossRefGoogle Scholar
  11. 11.
    Cannon TL, Lai DW, Hirsch D, Delacure M, Downey A, Kerr AR, Bannan M, Andreopoulou E, Safra T, Muggia F (2012) Squamous cell carcinoma of the oral cavity in nonsmoking women: a new and unusual complication of chemotherapy for recurrent ovarian cancer? Oncologist 17(12):1541–1546CrossRefGoogle Scholar
  12. 12.
    Matsuo K, Blake EA, Yessaian AA, Roman LD (2012) Long-term pegylated liposomal doxorubicin use and oromaxillary squamous cell carcinoma in endometrial cancer. Oncologist 17(12):1598–1599CrossRefGoogle Scholar
  13. 13.
    Brougham ND, Dennett ER, Cameron R, Tan ST (2012) The incidence of metastasis from cutaneous squamous cell carcinoma and the impact of its risk factors. J Surg Oncol 106(7):811–815CrossRefGoogle Scholar
  14. 14.
    Rogers HW, Weinstock MA, Feldman SR, Coldiron BM (2015) Incidence estimate of nonmelanoma skin cancer (Keratinocyte Carcinomas) in the U.S. Population, 2012. JAMA dermatology 151(10):1081–1086.CrossRefGoogle Scholar
  15. 15.
    Berg D, Otley CC (2002) Skin cancer in organ transplant recipients: epidemiology, pathogenesis, and management. Journal of the American Academy of Dermatology 47(1):1–17; quiz 18–20.Google Scholar
  16. 16.
    Lichter MD, Karagas MR, Mott LA, Spencer SK, Stukel TA, Greenberg ER (2000) Therapeutic ionizing radiation and the incidence of basal cell carcinoma and squamous cell carcinoma. The New Hampshire Skin Cancer Study Group. Archives of dermatology 136(8):1007–1011.Google Scholar
  17. 17.
    Su F, Viros A, Milagre C, Trunzer K, Bollag G, Spleiss O, Reis-Filho JS, Kong X, Koya RC, Flaherty KT et al (2012) RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med 366(3):207–215CrossRefGoogle Scholar
  18. 18.
    Wong SS, Tan KC, Goh CL (1998) Cutaneous manifestations of chronic arsenicism: review of seventeen cases. J Am Acad Dermatol 38(2 Pt 1):179–185CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Medicine, Division of Hematology, Oncology, and TransplantationUniversity of Minnesota Medical SchoolMinneapolisUSA
  2. 2.Hennepin County Medical CenterMinneapolisUSA
  3. 3.Department of PathologyUniversity of Minnesota Medical SchoolMinneapolisUSA
  4. 4.Department of DermatologyUniversity of Minnesota Medical SchoolMinneapolisUSA
  5. 5.Thedacare, AppletonUSA

Personalised recommendations