Advertisement

Bevacizumab Plus Direct Oral Anticoagulant Therapy in Ovarian Cancer Patients with Distal Deep Vein Thrombosis

  • Shinichi KomiyamaEmail author
  • Masaru Nagashima
  • Tomoko Taniguchi
  • Takayuki Rikitake
  • Mineto Morita
Short Communication
  • 7 Downloads

Abstract

Background and Objective

Administration of bevacizumab to ovarian cancer patients with distal deep vein thrombosis (DVT) is problematic because of lack of evidence about the likely outcomes. We conducted a preliminary study in ovarian cancer patients with DVT who received bevacizumab combined with a direct oral anticoagulant (DOAC).

Methods

We retrospectively investigated patients with advanced or recurrent epithelial ovarian cancer and distal DVT diagnosed by ultrasonography who underwent chemotherapy containing bevacizumab (15 mg/kg every 3 weeks) combined with DOAC therapy.

Results

Bevacizumab was administered to 88 patients, including 7 patients (7.9%) receiving concomitant DOAC therapy for distal DVT. In these 7 patients, the median body mass index was 21.3 kg/m2, median D-dimer level at diagnosis of DVT was 4.3 µg/mL, and median duration of DOAC therapy was 8 months. Adverse events during DOAC therapy were grade 1 epistaxis and grade 1 hemorrhoidal bleeding in one patient each. DVT resolved in four patients and was unchanged in three patients, with no central progression or secondary thromboembolism.

Conclusion

In ovarian cancer patients who have distal DVT, bevacizumab can possibly be administered safely when combined with a DOAC. To confirm this finding, further investigation on a larger scale will be required.

Notes

Acknowledgements

This work was supported by JSPS KAKENHI Grant-in-Aid for Scientific Research (C) Grant Number JP18K09302.

Compliance with Ethical Standards

Funding

This work was supported by JSPS KAKENHI Grant-in-Aid for Scientific Research (C) Grant Number JP18K09302.

Conflict of interest

SK received speaker’s honoraria from Chugai Pharmaceutical. The other authors do not have any potential conflict of interest.

Ethical approval

This was a retrospective study and our institutional ethics committee waived formal assessment of the protocol.

Informed consent

This was a retrospective study and our institutional ethics committee waived the need to obtain informed consent.

References

  1. 1.
    Cohen A, Lim CS, Davies AH. Venous thromboembolism in gynecological malignancy. Int J Gynecol Cancer. 2017;27:1970–8.CrossRefGoogle Scholar
  2. 2.
    Mereu L, Tateo S, Klersy C, Martinotti Gabellotti E, Polatti F. Stratification of venous thromboembolism risk in ovarian cancer patients during chemotherapy. Int J Gynecol Cancer. 2009;19:79–83.CrossRefGoogle Scholar
  3. 3.
    Abu Saadeh F, Norris L, O’Toole S, Gleeson N. Venous thromboembolism in ovarian cancer: incidence, risk factors and impact on survival. Eur J Obstet Gynecol Reprod Biol. 2013;170:214–8.CrossRefGoogle Scholar
  4. 4.
    Khorana AA. Venous thromboembolism and prognosis in cancer. Thromb Res. 2010;125:490–3.CrossRefPubMedCentralGoogle Scholar
  5. 5.
    Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Birrer MJ, Liang SX, Gynecologic Oncology Group. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365:2473–83.CrossRefGoogle Scholar
  6. 6.
    Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Kurzeder C, du Bois A, Sehouli J, Kimmig R, Stähle A, Collinson F, Essapen S, Gourley C, Lortholary A, Selle F, Mirza MR, Leminen A, Plante M, Stark D, Qian W, Parmar MK, Oza AM, ICON7 Investigators. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011;365:2484–96.CrossRefGoogle Scholar
  7. 7.
    Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-Coquard I. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA open-label randomized phase III trial. J Clin Oncol. 2014;32:1302–8.CrossRefGoogle Scholar
  8. 8.
    Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, Huisman M, King CS, Morris TA, Sood N, Stevens SM, Vintch JRE, Wells P, Woller SC, Moores L. Antithrombotic therapy for VTE disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149:315–52.CrossRefGoogle Scholar
  9. 9.
    Wu AR, Garry J, Labropoulos N. Incidence of pulmonary embolism in patients with isolated calf deep vein thrombosis. J Vasc Surg Venous Lymphat Disord. 2017;5:274–9.CrossRefGoogle Scholar
  10. 10.
    EINSTEIN Investigators, Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, Gallus AS, Lensing AW, Misselwitz F, Prins MH, Raskob GE, Segers A, Verhamme P, Wells P, Agnelli G, Bounameaux H, Cohen A, Davidson BL, Piovella F, Schellong S. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363:2499–510.CrossRefGoogle Scholar
  11. 11.
    Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Porcari A, Raskob GE, Weitz JI, AMPLIFY-EXT Investigators. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013;368:699–708.CrossRefGoogle Scholar
  12. 12.
    Hokusai-VTE Investigators, Büller HR, Décousus H, Grosso MA, Mercuri M, Middeldorp S, Prins MH, Raskob GE, Schellong SM, Schwocho L, Segers A, Shi M, Verhamme P, Wells P. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013;369:1406–15.CrossRefGoogle Scholar
  13. 13.
    Wells PS, Hirsh J, Anderson DR, Lensing AW, Foster G, Kearon C, Weitz J, D’Ovidio R, Cogo A, Prandoni P. Accuracy of clinical assessment of deep-vein thrombosis. Lancet. 1995;345:1326–30.CrossRefGoogle Scholar
  14. 14.
    Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111:4902–7.CrossRefPubMedCentralGoogle Scholar
  15. 15.
    Gerotziafas GT, Taher A, Abdel-Razeq H, AboElnazar E, Spyropoulos AC, El Shemmari S, Larsen AK, Elalamy I, COMPASS–CAT Working Group. A predictive score for thrombosis associated with breast, colorectal, lung, or ovarian cancer: the prospective COMPASS-Cancer-Associated Thrombosis Study. Oncologist. 2017;22:1222–31.CrossRefPubMedCentralGoogle Scholar
  16. 16.
    Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm#ctc_40. Accessed 15 Aug 2018.
  17. 17.
    Aghajanian C, Blank SV, Goff BA, Judson PL, Teneriello MG, Husain A, Sovak MA, Yi J, Nycum LR. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012;30:2039–45.CrossRefPubMedCentralGoogle Scholar
  18. 18.
    Komiyama S, Kato K, Inokuchi Y, Takano H, Matsumoto T, Hongo A, Asai-Sato M, Arakawa A, Kamiura S, Tabata T, Takeshima N, Sugiyama T. Bevacizumab combined with platinum-taxane chemotherapy as first-line treatment for advanced ovarian cancer: a prospective observational study of safety and efficacy in Japanese patients (JGOG3022 trial). Int J Clin Oncol. 2019;24:103–14.  https://doi.org/10.1007/s10147-018-1319-y (Epub 2018 Jul 20).CrossRefGoogle Scholar
  19. 19.
    Schwarz T, Buschmann L, Beyer J, Halbritter K, Rastan A, Schellong S. Therapy of isolated calf muscle vein thrombosis: a randomized, controlled study. J Vasc Surg. 2010;52:1246–50.CrossRefGoogle Scholar
  20. 20.
    Palareti G, Cosmi B, Lessiani G, Rodorigo G, Guazzaloca G, Brusi C, Valdré L, Conti E, Sartori M, Legnani C. Evolution of untreated calf deep-vein thrombosis in high risk symptomatic outpatients: the blind, prospective CALTHRO study. Thromb Haemost. 2010;104:1063–70.CrossRefGoogle Scholar
  21. 21.
    Dentali F, Pegoraro S, Barco S, di Minno MND, Mastroiacovo D, Pomero F, Lodigiani C, Bagna F, Sartori M, Barillari G, Mumoli N, Napolitano M, Passamonti SM, Benedetti R, Ageno W, Di Nisio M. Clinical course of isolated distal deep vein thrombosis in patients with active cancer: a multicenter cohort study. J Thromb Haemost. 2017;15:1757–63.CrossRefGoogle Scholar
  22. 22.
    Galanaud JP, Sevestre MA, Pernod G, Genty C, Richelet S, Kahn SR, Boulon C, Terrisse H, Quéré I, Bosson JL. Long-term outcomes of cancer-related isolated distal deep vein thrombosis: the OPTIMEV study. J Thromb Haemost. 2017;15:907–16.CrossRefGoogle Scholar
  23. 23.
    Palareti G. How I treat isolated distal deep vein thrombosis (IDDVT). Blood. 2014;123:1802–9.CrossRefGoogle Scholar
  24. 24.
    Kearon C, Spencer FA, O’Keeffe D, Parpia S, Schulman S, Baglin T, Stevens SM, Kaatz S, Bauer KA, Douketis JD, Lentz SR, Kessler CM, Moll S, Connors JM, Ginsberg JS, Spadafora L, Julian JA, D-dimer Optimal Duration Study Investigators. D-dimer Optimal Duration Study Investigators. D-dimer testing to select patients with a first unprovoked venous thromboembolism who can stop anticoagulant therapy: a cohort study. Ann Intern Med. 2015;162:27–34.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Obstetrics and GynecologyToho University Faculty of MedicineTokyoJapan
  2. 2.Department of GynecologyToho University Ohashi Medical CenterTokyoJapan

Personalised recommendations