Skip to main content

Advertisement

SpringerLink
Log in

Does bevacizumab increase joint pain in patients with cancer? Results of the prospective observational BEVARTHRALGIA study

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

Abstract

Purpose

The occurrence of arthralgia and myalgia during treatment with bevacizumab (Bev) has been described but not spontaneously reported. We aimed to evaluate the frequency of arthralgia in patients treated with Bev and identify the risk factors.

Methods

In this observational prospective study, a self-administered questionnaire was distributed to patients at the initiation of Bev and at 3 and 6 months of treatment. Bev (5–15 mg/kg) was administered every 2 or 3 weeks, with or without chemotherapy.

Results

A total of 71 patients (42 with colorectal cancer, 22 with ovarian cancer, and 7 with lung cancer) were enrolled from January to November 2018. All patients completed the questionnaire at initiation, while only 56 (78.9%) and 36 (50.7%) patients completed the questionnaire at 3 and 6 months, respectively. The frequency of joint pain was 29.6% before Bev treatment and increased to 41.8% and 50% at 3 and 6 months, respectively, without reaching significance. The evolution of pain was significant according to the Common Terminology Criteria for Adverse Events grades (P = 0.032). No significant increase in the impact of pain on instrumental or elementary activities was observed over time. The frequency of arthralgia significantly increased at 3 months in patients with ovarian cancer versus those with colorectal cancer (odds ratio: 19.50; 95% confidence interval 4.53–83.98; P < 0.001).

Conclusions

Bev‑including regimens tend to be associated with a significant increase in the frequency of arthralgia in women treated for ovarian cancer. Physicians should be aware of this side effect.

Clinical trial number

NCT03455907, date of registration: March 7, 2018.

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
Fig. 3

Similar content being viewed by others

Data availability

Data are available upon request from the study sponsor (University Hospital, Lille) and from the principal investigator Anthony Turpin.

References

  1. Carmeliet P, Jain RK (2011) Molecular mechanisms and clinical applications of angiogenesis. Nature 473:298–307. https://doi.org/10.1038/nature10144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342. https://doi.org/10.1056/NEJMoa032691

    Article  CAS  PubMed  Google Scholar 

  3. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A et al (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542–2550. https://doi.org/10.1056/NEJMoa061884

    Article  CAS  PubMed  Google Scholar 

  4. Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G et al (2011) A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 365:2484–2496. https://doi.org/10.1056/NEJMoa1103799

    Article  CAS  PubMed  Google Scholar 

  5. Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H et al (2011) Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 365:2473–2483. https://doi.org/10.1056/NEJMoa1104390

    Article  CAS  PubMed  Google Scholar 

  6. Graceffa D, Maiani E, Pace A, Solivetti FM, Elia F, De Mutiis C et al (2012) Psoriatic arthritis during treatment with bevacizumab for anaplastic oligodendroglioma. Case Rep Rheumatol 2012:208606. https://doi.org/10.1155/2012/208606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Jaishuen A, Berrios-Rivera JP, Sirisabya N, Zheng HG, Li Y, Kavanagh JJ (2008) Erosive osteoarthritis during treatment with bevacizumab and paclitaxel in a patient with recurrent papillary serous carcinoma of the ovary. Int J Gynecol Cancer 18:379–383. https://doi.org/10.1111/j.1525-1438.2007.01023.x

    Article  CAS  PubMed  Google Scholar 

  8. Datta-Mitra A, Riar NK, Raychaudhuri SP (2014) Remission of psoriasis and psoriatic arthritis during bevacizumab therapy for renal cell cancer. Indian J Dermatol 59:632. https://doi.org/10.4103/0019-5154.143574

    Article  PubMed  PubMed Central  Google Scholar 

  9. Nagai T, Sato M, Kobayashi M, Yokoyama M, Tani Y, Mochida J (2014) Bevacizumab, an anti-vascular endothelial growth factor antibody, inhibits osteoarthritis. Arthritis Res Ther 16:427. https://doi.org/10.1186/s13075-014-0427-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Thairu N, Kiriakidis S, Dawson P, Paleolog E (2011) Angiogenesis as a therapeutic target in arthritis in 2011: learning the lessons of the colorectal cancer experience. Angiogenesis 14:223–234. https://doi.org/10.1007/s10456-011-9208-2

    Article  CAS  PubMed  Google Scholar 

  11. Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N (1999) VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med 5:623–628. https://doi.org/10.1038/9467

    Article  CAS  PubMed  Google Scholar 

  12. Ryan AM, Eppler DB, Hagler KE, Bruner RH, Thomford PJ, Hall RL et al (1999) Preclinical safety evaluation of rhuMAbVEGF, an antiangiogenic humanized monoclonal antibody. Toxicol Pathol 27:78–86. https://doi.org/10.1177/019262339902700115

    Article  CAS  PubMed  Google Scholar 

  13. U.S. department of health and human services (2017) Common terminology criteria for adverse events (CTCAE) Version 5.0. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. Accessed 15 January 2018

  14. Katz S, Ford AB, Moskowitz RW, Jackson BA, Jaffe MW (1963) Studies of illness in the aged: the index of ADL: a standardized measure of biological and psychosocial function. JAMA 185:914–919. https://doi.org/10.1001/jama.1963.03060120024016

    Article  CAS  PubMed  Google Scholar 

  15. Lawton MP, Brody EM (1969) Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 9:179–186

    Article  CAS  Google Scholar 

  16. Edwards IR, Aronson JK (2000) Adverse drug reactions: definitions, diagnosis, and management. Lancet 356:1255–1259. https://doi.org/10.1016/S0140-6736(00)02799-9

    Article  CAS  PubMed  Google Scholar 

  17. Bannwarth B (2010) Critères d’imputabilité des effets indésirables des médicaments. Rev du Rhum 77:173–175. http://www.sciencedirect.com/science/article/pii/S187862271000041X. Accessed Apr 2010

  18. Benedek TG (1988) Neoplastic associations of rheumatic diseases and rheumatic manifestations of cancer. Clin Geriatr Med 4:333–355

    Article  CAS  Google Scholar 

  19. Manzini CU, Colaci M, Ferri C, Manzini E (2018) Paraneoplastic rheumatic disorders: a narrative review. Reumatismo 70:199–211. https://doi.org/10.4081/reumatismo.2018.1069

    Article  CAS  PubMed  Google Scholar 

  20. Fernandes R, Mazzarello S, Joy AA, Pond GR, Hilton J, Ibrahim MFK et al (2018) Taxane acute pain syndrome (TAPS) in patients receiving chemotherapy for breast or prostate cancer: a prospective multi-center study. Support Care Cancer 26:3073–3081. https://doi.org/10.1007/s00520-018-4161-x

    Article  CAS  PubMed  Google Scholar 

  21. Bondarenko IM, Bias P, Buchner A (2016) Incidence of bone pain in patients with breast cancer treated with lipegfilgrastim or pegfilgrastim: an integrated analysis from phase II and III studies. Support Care Cancer 24:267–273. https://doi.org/10.1007/s00520-015-2777-7

    Article  CAS  PubMed  Google Scholar 

  22. Watt FE (2018) Musculoskeletal pain and menopause. Post Reprod Health 24:34–43. https://doi.org/10.1177/2053369118757537

    Article  PubMed  Google Scholar 

  23. Touyz RM, Herrmann SMS, Herrmann J (2018) Vascular toxicities with VEGF inhibitor therapies–focus on hypertension and arterial thrombotic events. J Am Soc Hypertens 12:409–425. https://doi.org/10.1016/j.jash.2018.03.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Totzeck M, Mincu RI, Rassaf T (2017) Cardiovascular adverse events in patients with cancer treated with bevacizumab: a meta-analysis of more than 20 000 patients. J Am Heart Assoc 6:e006278. https://doi.org/10.1161/JAHA.117.006278

    Article  PubMed  PubMed Central  Google Scholar 

  25. Lee S-P, Hsu H-C, Tai Y-J, Chen Y-L, Chiang Y-C, Chen C-A et al (2019) Bevacizumab dose affects the severity of adverse events in gynecologic malignancies. Front Pharmacol 10:426. https://doi.org/10.3389/fphar.2019.00426

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ventriglia J, Paciolla I, Pisano C, Tambaro R, Cecere SC, Di Napoli M et al (2020) Arthralgia in patients with ovarian cancer treated with bevacizumab and chemotherapy. Int J Gynecol Cancer. https://doi.org/10.1136/ijgc-2020-001540

    Article  PubMed  Google Scholar 

  27. Giannakopoulos CK, Kyriakidou GK, Toufexi GE (2005) Palmar fasciitis and polyarthritis associated with secondary ovarian carcinoma. Case report Eur J Gynaecol Oncol 26:339–341

    PubMed  Google Scholar 

  28. Martorell EA, Murray PM, Peterson JJ, Menke DM, Calamia KT (2004) Palmar fasciitis and arthritis syndrome associated with metastatic ovarian carcinoma: a report of four cases. J Hand Surg Am 29:654–660. https://doi.org/10.1016/j.jhsa.2004.04.012

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank all patients who participated in the BEVARTHRALGIA study. We also thank Severine Marchant (Center Oscar Lambret) and Editage (www.editage.com) for English language editing.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Author notes

  1. Marie-Hélène Vieillard and Anthony Turpin contributed equally to this work.

Authors and Affiliations

  1. Medical Oncology Department, CHU Lille, University of Lille, Lille, France

    Enora Vauléon

  2. ULR 2694, METRICS: Évaluation des Technologies de santé et des Pratiques Médicales, University Lille, CHU Lille, Lille, France

    Hélène Behal

  3. Department of Medical Oncology, Oscar Lambret Center, Lille, France

    Loïc Lebellec

  4. Hôpital Duchenne, Boulogne sur mer, France

    Renaud Desbarbieux

  5. CNRS, Inserm, Institut Pasteur de Lille, UMR9020, UMR-S 1277, Canther, Cancer Heterogeneity, Plasticity and Resistance to Therapies, Thoracic Oncology Department, CHU Lille, University of Lille, Lille, France

    Simon Baldacci

  6. ULR 7365-GRITA-Groupe de Recherche Sur Les Formes Injectables et les Technologies Associées, University Lille, CHU Lille, 59000, Lille, France

    Nicolas Simon

  7. Department of Medical Oncology, Oscar Lambret Center, Lille, France

    Diane Pannier & Marie-Hélène Vieillard

  8. CNRS, Inserm, Institut Pasteur de Lille, UMR9020, UMR-S 1277, Canther, Cancer Heterogeneity, Plasticity and Resistance To Therapies, University Department of Rheumatology, University of Lille, CHU Lille, Lille, France

    Marie-Hélène Vieillard

  9. CNRS, Inserm, Institut Pasteur de Lille, UMR9020, UMR-S 1277, Canther, Cancer Heterogeneity, Plasticity and Resistance To Therapies, Medical Oncology Department, University of Lille, CHU Lille, Lille, France

    Anthony Turpin

Authors
  1. Enora Vauléon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hélène Behal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Loïc Lebellec
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Renaud Desbarbieux
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Simon Baldacci
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nicolas Simon
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Diane Pannier
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Marie-Hélène Vieillard
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Anthony Turpin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

M-HV: conceptualization, methodology, reviewing, and editing. AT: methodology, supervision, writing—reviewing, and editing. EV: data curation, writing—original draft preparation. RD and LL: visualization, investigation, writing, reviewing, and editing. HB: methodology, formal analysis, writing, reviewing, and editing. DP, NS, and SB: writing, reviewing, and editing.

Corresponding author

Correspondence to Anthony Turpin.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Ethics approval

The ethics committee at each participating center approved the study and follow-up protocol.

Consent to participate

All patients provided written informed consent before inclusion.

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 (PDF 756 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vauléon, E., Behal, H., Lebellec, L. et al. Does bevacizumab increase joint pain in patients with cancer? Results of the prospective observational BEVARTHRALGIA study. Cancer Chemother Pharmacol 87, 533–541 (2021). https://doi.org/10.1007/s00280-020-04226-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-020-04226-6

Keywords

Search

Navigation