SpringerLink
Log in

Cabozantinib-induced serum creatine kinase elevation and rhabdomyolysis: a retrospective case series

  • Short Communication
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Rhabdomyolysis, which is primarily characterized by serum creatine kinase (CK) elevation, is a potentially fatal disease, and it can occur in a variety of etiologies, including drug-induced. Cabozantinib is one of the standard treatments for patients with renal cell carcinoma (RCC). This retrospective case series aimed to investigate the frequency of cabozantinib-induced CK elevation and rhabdomyolysis, and to reveal their detailed clinical features.

Methods

To investigate the frequency of cabozantinib-induced serum CK elevation and rhabdomyolysis, we retrospectively reviewed the clinical information and laboratory data of the patients with advanced RCC who received cabozantinib monotherapy at our institution from April 2020 to April 2023. Data were retrieved from the electronic medical records and the RCC database of our institution. Primary endpoint of the current case series was the frequency of CK elevation and rhabdomyolysis.

Results

Sixteen patients were retrieved form the database and 13 were included in the case series (excluded by clinical trial enrollment [n = 2] and short-term administration [n = 1]). Eight (61.5%) patients among them experienced serum CK elevation, including five patients who were classified into grade 1. CK elevation occurred a median of 14 days after initiation of cabozantinib. Two patients with grade 2 or 3 of CK elevation developed rhabdomyolysis with muscle weakness and/or acute kidney injury.

Conclusions

CK elevation may frequently happen during cabozantinib treatment, and in most cases, it may be asymptomatic and may not be clinically problematic. However, medical providers should be aware that symptomatic CK elevations suggestive of rhabdomyolysis may occasionally occur.

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
EUR 32.99 /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 includes VAT (Brazil)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Availability of data and materials

The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request.

Abbreviations

CK:

Creatine kinase

VEGFR:

Vascular endothelial growth factor receptor

RCC:

Renal cell carcinoma

ICI:

Immune checkpoint inhibitor

CTCAE:

Common terminology criteria for adverse events

irAE:

Immune-related adverse event

References

  1. Moghadam-Kia S, Oddis CV, Aggarwal R (2016) Approach to asymptomatic creatine kinase elevation. Cleve Clin J Med 83(1):37–42. https://doi.org/10.3949/ccjm.83a.14120

    Article  PubMed  PubMed Central  Google Scholar 

  2. Adenis A, Bouche O, Bertucci F, Kalbacher E, Fournier C, Cassier P, Collard O, Bay JO, Italiano A, Chevreau C, Clisant S, Kramar A, Blay JY, Penel N (2012) Serum creatine kinase increase in patients treated with tyrosine kinase inhibitors for solid tumors. Med Oncol 29(4):3003–3008. https://doi.org/10.1007/s12032-012-0204-1

    Article  CAS  PubMed  Google Scholar 

  3. Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov F, Hammers H, Hutson TE, Lee JL, Peltola K, Roth BJ, Bjarnason GA, Geczi L, Keam B, Maroto P, Heng DY, Schmidinger M, Kantoff PW, Borgman-Hagey A, Hessel C, Scheffold C, Schwab GM, Tannir NM, Motzer RJ, M Investigators (2015) Cabozantinib versus everolimus in advanced renal-cell carcinoma. N Engl J Med 373(19):1814–1823. https://doi.org/10.1056/NEJMoa1510016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Choueiri TK, Halabi S, Sanford BL, Hahn O, Michaelson MD, Walsh MK, Feldman DR, Olencki T, Picus J, Small EJ, Dakhil S, George DJ, Morris MJ (2017) Cabozantinib versus sunitinib as initial targeted therapy for patients with metastatic renal cell carcinoma of poor or intermediate risk: the alliance A031203 CABOSUN trial. J Clin Oncol 35(6):591–597. https://doi.org/10.1200/JCO.2016.70.7398

    Article  CAS  PubMed  Google Scholar 

  5. Tomita Y, Tatsugami K, Nakaigawa N, Osawa T, Oya M, Kanayama H, Nakayama Kondoh C, Sassa N, Nishimura K, Nozawa M, Masumori N, Miyoshi Y, Kuroda S, Tanaka S, Kimura A, Tamada S (2020) Cabozantinib in advanced renal cell carcinoma: a phase II, open-label, single-arm study of Japanese patients. Int J Urol 27(11):952–959. https://doi.org/10.1111/iju.14329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Suzuki S, Ishikawa N, Konoeda F, Seki N, Fukushima S, Takahashi K, Uhara H, Hasegawa Y, Inomata S, Otani Y, Yokota K, Hirose T, Tanaka R, Suzuki N, Matsui M (2017) Nivolumab-related myasthenia gravis with myositis and myocarditis in Japan. Neurology 89(11):1127–1134. https://doi.org/10.1212/WNL.0000000000004359

    Article  CAS  PubMed  Google Scholar 

  7. Psimaras D (2018) Neuromuscular complications of immune checkpoint inhibitors. Presse Med 47(11–12 Pt 2):e253–e259. https://doi.org/10.1016/j.lpm.2018.10.009

    Article  PubMed  Google Scholar 

  8. Safa H, Johnson DH, Trinh VA, Rodgers TE, Lin H, Suarez-Almazor ME, Fa’ak F, Saberian C, Yee C, Davies MA, Tummala S, Woodman K, Abdel-Wahab N, Diab A (2019) Immune checkpoint inhibitor related myasthenia gravis: single center experience and systematic review of the literature. J Immunother Cancer 7(1):319. https://doi.org/10.1186/s40425-019-0774-y

    Article  PubMed  PubMed Central  Google Scholar 

  9. Stump SE, Whang YE, Crona DJ (2018) Cabozantinib-induced serum creatine kinase elevation and musculoskeletal complaints. Invest New Drugs 36(6):1143–1146. https://doi.org/10.1007/s10637-018-0629-2

    Article  CAS  PubMed  Google Scholar 

  10. Okubo H, Ando H, Takasaki Y, Nakadera E, Fukuo Y, Shiina S, Ikejima K (2022) Impact of cabozantinib exposure on proteinuria and muscle toxicity in patients with unresectable hepatocellular carcinoma. Pharmaceuticals (Basel). https://doi.org/10.3390/ph15121460

    Article  PubMed  Google Scholar 

  11. Ge Y, Waldemer RJ, Nalluri R, Nuzzi PD, Chen J (2013) Flt3L is a novel regulator of skeletal myogenesis. J Cell Sci 126(Pt 15):3370–3379. https://doi.org/10.1242/jcs.123950

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Usuki K, Sakura T, Kobayashi Y, Miyamoto T, Iida H, Morita S, Bahceci E, Kaneko M, Kusano M, Yamada S, Takeshita S, Miyawaki S, Naoe T (2018) Clinical profile of gilteritinib in Japanese patients with relapsed/refractory acute myeloid leukemia: an open-label phase 1 study. Cancer Sci 109(10):3235–3244. https://doi.org/10.1111/cas.13749

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Cerbone L, Combarel D, Geraud A, Auclin E, Foulon S, Alves Costa Silva C, Colomba E, Carril L, Derosa L, Flippot R, Mir O, Khoudour N, Blanchet B, Escudier B, Paci A, Albiges L (2021) Association of cabozantinib pharmacokinetics, progression and toxicity in metastatic renal cell carcinoma patients: results from a pharmacokinetics/pharmacodynamics study. ESMO Open 6(6):100312. https://doi.org/10.1016/j.esmoop.2021.100312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Nguyen L, Holland J, Ramies D, Mamelok R, Benrimoh N, Ciric S, Marbury T, Preston RA, Heuman DM, Gavis E, Lacy S (2016) Effect of renal and hepatic impairment on the pharmacokinetics of cabozantinib. J Clin Pharmacol 56(9):1130–1140. https://doi.org/10.1002/jcph.714

    Article  CAS  PubMed  Google Scholar 

  15. Salem JE, Manouchehri A, Moey M, Lebrun-Vignes B, Bastarache L, Pariente A, Gobert A, Spano JP, Balko JM, Bonaca MP, Roden DM, Johnson DB, Moslehi JJ (2018) Cardiovascular toxicities associated with immune checkpoint inhibitors: an observational, retrospective, pharmacovigilance study. Lancet Oncol 19(12):1579–1589. https://doi.org/10.1016/S1470-2045(18)30608-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Allenbach Y, Anquetil C, Manouchehri A, Benveniste O, Lambotte O, Lebrun-Vignes B, Spano JP, Ederhy S, Klatzmann D, Rosenzwajg M, Fautrel B, Cadranel J, Johnson DB, Moslehi JJ, Salem JE (2020) Immune checkpoint inhibitor-induced myositis, the earliest and most lethal complication among rheumatic and musculoskeletal toxicities. Autoimmun Rev 19(8):102586. https://doi.org/10.1016/j.autrev.2020.102586

    Article  CAS  PubMed  Google Scholar 

  17. Ruggeri EM, Cecere FL, Moscetti L, Doni L, Padalino D, Di Costanzo F (2010) Severe rhabdomyolysis during sunitinib treatment of metastatic renal cell carcinoma. A report of two cases. Ann Oncol 21(9):1926–1927. https://doi.org/10.1093/annonc/mdq395

    Article  CAS  PubMed  Google Scholar 

  18. Liman AD, Passero VA, Liman AK, Shields J (2018) A rare case of sunitinib-induced rhabdomyolysis in renal cell carcinoma. Case Rep Oncol Med 2018:3808523. https://doi.org/10.1155/2018/3808523

    Article  PubMed  PubMed Central  Google Scholar 

  19. Logue JM, Kiani B, Bitting RL (2017) Pazopanib and statin-induced rhabdomyolysis. Case Rep Oncol 10(3):954–957. https://doi.org/10.1159/000481659

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to thank the patients who participated in this study.

Funding

This study was not supported by any funding agencies.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Toranomon Hospital, 2-2-2 Toranomon Minato-ku, Tokyo, 105-8470, Japan

    Taro Yamanaka, Kohji Takemura, Koichi Suyama & Yuji Miura

  2. Department of Urology, Toranomon Hospital, Tokyo, Japan

    Michikata Hayashida & Shinji Urakami

Authors
  1. Taro Yamanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kohji Takemura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michikata Hayashida
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Koichi Suyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shinji Urakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yuji Miura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yuji Miura.

Ethics declarations

Conflict of interest

There are no conflicts of interest to declare except for Yuji Miura: personal fees from Ono Pharmaceutical, Bristol Myers Squibb, MSD, and Takeda; Advisory Board personal member of Chugai Pharmaceutical Co. and Takeda; local PI and institutional financial interests from MSD and Ono Pharmaceutical. All of these were outside the submitted work.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (XLSX 14 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yamanaka, T., Takemura, K., Hayashida, M. et al. Cabozantinib-induced serum creatine kinase elevation and rhabdomyolysis: a retrospective case series. Cancer Chemother Pharmacol 92, 235–240 (2023). https://doi.org/10.1007/s00280-023-04557-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-023-04557-0

Keywords

Search

Navigation