Skip to main content

Advertisement

SpringerLink
Log in

Risk factors for pegylated liposomal doxorubicin-induced palmar-plantar erythrodysesthesia over time: assessment of monocyte count and baseline clinical parameters

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

Abstract

Purpose

Pegylated liposomal doxorubicin (PLD) is widely used in relapsing ovarian carcinoma. Its original formulation is metabolized by the monocyte–macrophage system. One of its main toxicities is the palmoplantar erythrodysesthesia (PPE) syndrome. To date, no predictive factors of PPE have been identified.

Methods

Data of patients (pts) treated with PLD between 2005 and 2014 were retrospectively collected. A case–control study was performed, comparing main baseline clinical and biological characteristics of pts experiencing PPE and those who did not, after at least three cycles of PLD. A pilot analysis of blood monocyte subpopulations (classical, intermediate and non-classical) was performed by FACS in selected pts.

Results

Among 88 pts treated with PLD, 28 experienced PPE of any grade (31, 95 % CI 21–41). The first occurrence of PPE was at first cycle in only 11 % of pts, peaked at cycle 2 (32 %) and represented 57 % of cases after cycle 3. Baseline characteristics of pts with PPE were compared to 27 control pts who received at least 3 cycles. Older pts represented 61 % of pts with PPE and 15 % of pts without PPE (p = 0.04 by Chi-square test). Monocyte count and inflammatory parameters were not associated with PPE. However, the analysis of monocyte subpopulations revealed a large inter-patient variability.

Conclusion

Contrary to most acute toxicities, PPE occurred more frequently after several cycles, suggesting a PLD body accumulation through repeated cycles. PPE was more frequent in pts older than 70 years. Monocyte subpopulations may have different roles on PLD metabolism and warrant further studies.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Allen TM, Francis JM (2004) Advantages of Liposomal Delivery Systems for Anthracyclines. Semin Oncol 31(6 Suppl 13):5–15

    Article  CAS  PubMed  Google Scholar 

  2. Zamboni WC (2008) Concept and clinical evaluation of carrier-mediated anticancer agents. Oncologist 13(3):248–260. doi:10.1634/theoncologist.2007-0180

    Article  CAS  PubMed  Google Scholar 

  3. Zamboni WC, Maruca LJ, Strychor S, Zamboni BA, Ramalingam S, Edwards RP, Kim J et al (2011) Bidirectional pharmacodynamic interaction between pegylated liposomal CKD-602 (S-CKD602) and monocytes in patients with refractory solid tumors. J Liposome Res 21(2):158–165. doi:10.3109/08982104.2010.496085

    Article  CAS  PubMed  Google Scholar 

  4. Pujade-Lauraine E, Wagner U, Aavall-Lundqvist E, Gebski V, Heywood M, Vasey PA, Volgger B et al (2010) Pegylated liposomal doxorubicin and carboplatin compared with paclitaxel and carboplatin for patients with platinum-sensitive ovarian cancer in late relapse. J Clin Oncol 28(20):3323–3329. doi:10.1200/JCO.2009.25.7519

    Article  CAS  PubMed  Google Scholar 

  5. Duggan ST, Keating GM (2011) Pegylated liposomal doxorubicin: a review of its use in metastatic breast cancer, ovarian cancer, multiple myeloma and AIDS-related Kaposi’s sarcoma. Drugs 71(18):2531–2558. doi:10.2165/11207510-000000000-00000

    Article  CAS  PubMed  Google Scholar 

  6. Lotrionte M, Palazzoni G, Abbate A, De Marco E, Mezzaroma E, Di Persio S, Frati G, Loperfido F, Biondi-Zoccai G (2013) Cardiotoxicity of a non-pegylated liposomal doxorubicin-based regimen versus an epirubicin-based regimen for breast cancer: the LITE (liposomal doxorubicin-investigational chemotherapy-tissue doppler imaging evaluation) randomized pilot study. Int J Cardiol 167(3):1055–1057. doi:10.1016/j.ijcard.2012.10.079

    Article  PubMed  Google Scholar 

  7. Sparano JA, Makhson AN, Semiglazov VF, Tjulandin SA, Balashova OL, Bondarenko IN, Bogdanova NV et al (2009) Pegylated liposomal doxorubicin plus docetaxel significantly improves time to progression without additive cardiotoxicity compared with docetaxel monotherapy in patients with advanced breast cancer previously treated with neoadjuvant-adjuvant anthracycline therapy: results from a randomized phase III study. J Clin Oncol 27(27):4522–4529. doi:10.1200/JCO.2008.20.5013

    Article  CAS  PubMed  Google Scholar 

  8. Berry G, Billingham M, Alderman E, Richardson P, Torti F, Lum B, Patek A, Martin FJ (1998) The use of cardiac biopsy to demonstrate reduced cardiotoxicity in AIDS kaposi’s sarcoma patients treated with pegylated liposomal doxorubicin. Ann Oncol 9(7):711–716

    Article  CAS  PubMed  Google Scholar 

  9. Lorusso D, Di Stefano A, Carone V, Fagotti A, Pisconti S, Scambia G (2007) Pegylated liposomal doxorubicin-related palmar-plantar erythrodysesthesia (‘hand-foot’ syndrome). Ann Oncol 18(7):1159–1164. doi:10.1093/annonc/mdl477

    Article  CAS  PubMed  Google Scholar 

  10. Gordon AN, Fleagle JT, Guthrie D, Parkin DE, Gore ME, Lacave AJ (2001) Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol 19(14):3312–3322

    CAS  PubMed  Google Scholar 

  11. La-Beck NM, Zamboni BA, Gabizon A, Schmeeda H, Amantea M, Gehrig PA, Zamboni WC (2012) Factors affecting the pharmacokinetics of pegylated liposomal doxorubicin in patients. Cancer Chemother Pharmacol 69(1):43–50. doi:10.1007/s00280-011-1664-2

    Article  CAS  PubMed  Google Scholar 

  12. Gusella M, Bononi A, Modena Y, Bertolaso L, Franceschetti P, Menon D, Pezzolo E et al (2014) Age affects pegylated liposomal doxorubicin elimination and tolerability in patients over 70 years old. Cancer Chemother Pharmacol 73(3):517–524. doi:10.1007/s00280-014-2378-z

    Article  CAS  PubMed  Google Scholar 

  13. Wong KL, Tai JJ, Wong WC, Han H, Sem X, Yeap WH, Kourilsky P, Wong SC (2011) Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets. Blood 118(5):e16–e31. doi:10.1182/blood-2010-12-326355

    Article  CAS  PubMed  Google Scholar 

  14. Kurtz JE, Kaminsky MC, Floquet A, Veillard AS, Kimmig R, Dorum A, Elit L, Intergroup Gynecologic Cancer et al (2011) Ovarian cancer in elderly patients: carboplatin and pegylated liposomal doxorubicin versus carboplatin and paclitaxel in late relapse: a Gynecologic Cancer Intergroup (GCIG) CALYPSO sub-study. Ann Oncol Off J Eur Soci Med Oncol ESMO 22(11):2417–2423. doi:10.1093/annonc/mdr001

    Article  CAS  Google Scholar 

  15. Ko EM, Lippmann Q, Caron WP, Zamboni W, Gehrig PA (2013) Clinical risk factors of PEGylated liposomal doxorubicin induced palmar plantar erythrodysesthesia in recurrent ovarian cancer patients. Gynecol Oncol 131(3):683–688. doi:10.1016/j.ygyno.2013.09.031

    Article  CAS  PubMed  Google Scholar 

  16. Tanyi JL, Smith JA, Ramos L, Parker CL, Munsell MF, Wolf JK (2009) Predisposing risk factors for palmar-plantar erythrodysesthesia when using liposomal doxorubicin to treat recurrent ovarian cancer. Gynecol Oncol 114(2):219–224. doi:10.1016/j.ygyno.2009.04.007

    Article  CAS  PubMed  Google Scholar 

  17. Gordinier ME, Dizon DS, Fleming EL, Weitzen S, Schwartz J, Parker LP, Granai CO (2006) Elevated body mass index does not increase the risk of palmar–plantar erythrodysesthesia in patients receiving pegylated liposomal doxorubicin. Gynecol Oncol 103(1):72–74. doi:10.1016/j.ygyno.2006.01.031

    Article  CAS  PubMed  Google Scholar 

  18. Gordon S, Taylor PR (2005) Monocyte and macrophage heterogeneity. Nat Rev Immunol 5(12):953–964. doi:10.1038/nri1733

    Article  CAS  PubMed  Google Scholar 

  19. Auffray C, Sieweke MH, Geissmann F (2009) Blood monocytes: development, heterogeneity, and relationship with dendritic cells. Annu Rev Immunol 27:669–692. doi:10.1146/annurev.immunol.021908.132557

    Article  CAS  PubMed  Google Scholar 

  20. Qian BZ, Li J, Zhang H, Kitamura T, Zhang J, Campion LR, Kaiser EA, Snyder LA, Pollard JW (2011) CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature 475(7355):222–225. doi:10.1038/nature10138

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Wynn TA, Chawla A, Pollard JW (2013) Origins and hallmarks of macrophages: development, homeostasis, and disease. Nature 496(7446):445–455. doi:10.1038/nature12034

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Supported by the Medical Oncology department and Haematology department of Cochin-Port Royal Hospital.

Author information

Author notes

  1. George Emile

    Present address: Medical Oncology Department, Beaujon Hospital, Clichy, France

Authors and Affiliations

  1. Medical Oncology Department, CAncer PErsonalized Medicine, Cochin – Port Royal Hospital, Sorbonne Paris Cité University, Paris, France

    Zahra Ajgal, George Emile, Anatole Cessot, Jean Marie Tigaud, Olivier Huillard, Pascaline Boudou-Rouquette, Francois Goldwasser & Jerome Alexandre

  2. Haematology Department, CAncer PErsonalized Medicine, Cochin – Port Royal Hospital, Sorbonne Paris Cité University, Paris, France

    Nicolas Chapuis & Michaela Fontenay

Authors
  1. Zahra Ajgal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nicolas Chapuis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. George Emile
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anatole Cessot
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jean Marie Tigaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Olivier Huillard
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Pascaline Boudou-Rouquette
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Michaela Fontenay
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Francois Goldwasser
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jerome Alexandre
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jerome Alexandre.

Ethics declarations

Conflict of interest

None declared.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ajgal, Z., Chapuis, N., Emile, G. et al. Risk factors for pegylated liposomal doxorubicin-induced palmar-plantar erythrodysesthesia over time: assessment of monocyte count and baseline clinical parameters. Cancer Chemother Pharmacol 76, 1033–1039 (2015). https://doi.org/10.1007/s00280-015-2875-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-015-2875-8

Keywords

Search

Navigation