Advertisement

Journal of Gastrointestinal Cancer

, Volume 50, Issue 4, pp 943–946 | Cite as

Pazopanib Monotherapy Is Active in Relapsed and Refractory Metastatic Gastroesophageal Adenocarcinoma and Can Produce Durable Response

  • Vineet Govinda GuptaEmail author
  • Ranga Rao Rangaraju
  • Rajat Saha
  • Peush Bajpai
Case Report
  • 14 Downloads

Background

Metastatic gastroesophageal adenocarcinomas (GEA) constitute a challenging treatment problem. Two-thirds of all patients will either present with or develop metastatic disease over the course of their therapy. Despite advances in treatment, the prognosis of metastatic GEA remains poor with a median survival of less than 1 year, except perhaps for HER2/neu-amplified patients who can achieve better outcomes with the integration of HER2-directed targeted therapy [1]. The standard systemic therapy for metastatic GEA comprises palliative-intent chemotherapy, with multiple active agents given in several sequential “lines” of therapy. The most active agents tend to be platinum agents, fluoropyrimidines, and taxanes. However, fitness for chemotherapy, response rates, and progression-free survival drops from one line to the next due to disease progression and side effects of previous treatment.

Angiogenesis plays an important role in gastric cancer growth and spread, and high...

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

For this type of study, formal consent is not required.

References

  1. 1.
    Shah MA. Update on metastatic gastric and esophageal cancers. J Clin Oncol Off J Am Soc Clin Oncol. 2015;33:1760–9.  https://doi.org/10.1200/JCO.2014.60.1799.CrossRefGoogle Scholar
  2. 2.
    Kim S-E, Shim K-N, Jung S-A, Yoo K, Lee JH. The clinicopathological significance of tissue levels of hypoxia-inducible factor-1alpha and vascular endothelial growth factor in gastric cancer. Gut Liver. 2009;3:88–94.  https://doi.org/10.5009/gnl.2009.3.2.88.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Maeda K, Chung YS, Ogawa Y, Takatsuka S, Kang SM, Ogawa M, et al. Prognostic value of vascular endothelial growth factor expression in gastric carcinoma. Cancer. 1996;77:858–63.CrossRefGoogle Scholar
  4. 4.
    Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, et al. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol Off J Am Soc Clin Oncol. 2011;29:3968–76.  https://doi.org/10.1200/JCO.2011.36.2236.CrossRefGoogle Scholar
  5. 5.
    Shen L, Li J, Xu J, Pan H, Dai G, Qin S, et al. Bevacizumab plus capecitabine and cisplatin in Chinese patients with inoperable locally advanced or metastatic gastric or gastroesophageal junction cancer: randomized, double-blind, phase III study (AVATAR study). Gastric Cancer. 2015;18:168–76.  https://doi.org/10.1007/s10120-014-0351-5.CrossRefPubMedGoogle Scholar
  6. 6.
    Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383:31–9.  https://doi.org/10.1016/S0140-6736(13)61719-5.CrossRefGoogle Scholar
  7. 7.
    Wilke H, Muro K, Van Cutsem E, Oh S-C, Bodoky G, Shimada Y, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15:1224–35.  https://doi.org/10.1016/S1470-2045(14)70420-6.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Saito S, Muneoka Y, Ishikawa T, Akazawa K. Cost-effectiveness of paclitaxel + ramucirumab combination therapy for advanced gastric cancer progressing after first-line chemotherapy in Japan. Clin Ther. 2017;39:2380–8.  https://doi.org/10.1016/j.clinthera.2017.10.017.CrossRefPubMedGoogle Scholar
  9. 9.
    Chen L-T, Oh D-Y, Ryu M-H, Yeh K-H, Yeo W, Carlesi R, et al. Anti-angiogenic therapy in patients with advanced gastric and gastroesophageal junction cancer: a systematic review. Cancer Res Treat. 2017;49:851–68.  https://doi.org/10.4143/crt.2016.176.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Hamberg P, Verweij J, Sleijfer S. (Pre-)clinical pharmacology and activity of pazopanib, a novel multikinase angiogenesis inhibitor. Oncologist. 2010;15:539–47.  https://doi.org/10.1634/theoncologist.2009-0274.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Escudier B, Porta C, Bono P, Powles T, Eisen T, Sternberg CN, et al. Randomized, controlled, double-blind, cross-over trial assessing treatment preference for pazopanib versus sunitinib in patients with metastatic renal cell carcinoma: PISCES Study. J Clin Oncol Off J Am Soc Clin Oncol. 2014;32:1412–8.  https://doi.org/10.1200/JCO.2013.50.8267.CrossRefGoogle Scholar
  12. 12.
    Kim ST, Lee J, Lee SJ, Park SH, Jung S-H, Park YS, et al. Prospective phase II trial of pazopanib plus CapeOX (capecitabine and oxaliplatin) in previously untreated patients with advanced gastric cancer. Oncotarget. 2016;7:24088–96.  https://doi.org/10.18632/oncotarget.8175.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Burris HA, Dowlati A, Moss RA, Infante JR, Jones SF, Spigel DR, et al. Phase I study of pazopanib in combination with paclitaxel and carboplatin given every 21 days in patients with advanced solid tumors. Mol Cancer Ther. 2012;11:1820–8.  https://doi.org/10.1158/1535-7163.MCT-11-0997.CrossRefPubMedGoogle Scholar
  14. 14.
    Ulahannan SV, Brahmer JR. Antiangiogenic agents in combination with chemotherapy in patients with advanced non-small cell lung cancer. Cancer Investig. 2011;29:325–37.  https://doi.org/10.3109/07357907.2011.554476.CrossRefGoogle Scholar
  15. 15.
    Tan AR, Dowlati A, Stein MN, Jones SF, Infante JR, Bendell J, et al. Phase I study of weekly paclitaxel in combination with pazopanib and lapatinib in advanced solid malignancies. Br J Cancer. 2014;110:2647–54.  https://doi.org/10.1038/bjc.2014.233.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    du Bois A, Floquet A, Kim J-W, Rau J, del Campo JM, Friedlander M, et al. Incorporation of pazopanib in maintenance therapy of ovarian cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2014;32:3374–82.  https://doi.org/10.1200/JCO.2014.55.7348.CrossRefGoogle Scholar
  17. 17.
    Oza AM, Cook AD, Pfisterer J, Embleton A, Ledermann JA, Pujade-Lauraine E, et al. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol. 2015;16:928–36.  https://doi.org/10.1016/S1470-2045(15)00086-8.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365:2473–83.  https://doi.org/10.1056/NEJMoa1104390.CrossRefPubMedGoogle Scholar
  19. 19.
    Lopez-Chavez A, Young T, Fages S, Leon L, Schiller JH, Dowlati A, et al. Bevacizumab maintenance in patients with advanced non-small-cell lung cancer, clinical patterns, and outcomes in the Eastern Cooperative Oncology Group 4599 Study: results of an exploratory analysis. J Thorac Oncol. 2012;7:1707–12.  https://doi.org/10.1097/JTO.0b013e318265b500.CrossRefPubMedGoogle Scholar
  20. 20.
    Yu P, Huang L, Cheng G, Yang L, Dai G, Ying J, et al. Treatment strategy and prognostic factors for Krukenberg tumors of gastric origin: report of a 10-year single-center experience from China. Oncotarget. 2017;8:82558–70.  https://doi.org/10.18632/oncotarget.19759.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Kim ST, Jang H-L, Lee SJ, Lee J, Choi Y-L, Kim K-M, et al. Pazopanib, a novel multitargeted kinase inhibitor, shows potent in vitro antitumor activity in gastric cancer cell lines with FGFR2 amplification. Mol Cancer Ther. 2014;13:2527–36.  https://doi.org/10.1158/1535-7163.MCT-14-0255.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Vineet Govinda Gupta
    • 1
    Email author
  • Ranga Rao Rangaraju
    • 1
  • Rajat Saha
    • 2
  • Peush Bajpai
    • 1
  1. 1.Department of Medical OncologyMax Super Speciality HospitalNew DelhiIndia
  2. 2.Department of Medical OncologyMax Super Speciality HospitalNew DelhiIndia

Personalised recommendations