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Thalidomide Combined with Chemotherapy in Treating Patients with Advanced lung Cancer

  • Li, Li (Department of Chemotherapy, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research) ;
  • Huang, Xin-En (Department of Chemotherapy, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research)
  • Published : 2016.05.01

Abstract

Objectives: To evaluate efficacy and toxicity in patients with advanced lung cancer, including non-small cell and small cell variants (NSCLC and SCLC), treated with thalidomide plus chemotherapy. Methods: Fourteen patients with advanced lung cancer were scheduled to receive chemotherapy combined with thalidomide. All patients in this study received thalidomide (100 mg orally per night before sleeping, produced by Changzhou Pharmaceutical Factory Co.Ltd) after the start of chemotherapy for at least 14 days. Chemotherapy was administered according to the condition of patients. After at least 14 days of treatment, efficacy and toxicity were evaluated. Results: There were 6 female and 8 male patients with advanced lung cancer recruited into this study, including 2 with SCLC and 12 with NSCLC. The median age was 56.7 (44-65) years. Progressive disease was observed in 12 patients (12/14), and stable disease in 2 (2/14). Grade 1 to 2 myelosuppression was observed in 4/14 patients, and Grade 1 to 2 elevation of hepatic enzymes was recorded in 5/14 patients. Adverse effects on the gastrointestinal tract were documented in 2/14 patients, all beingGrade 1. No Grade 3-4 toxicity was recorded. No treatment related deaths occurred. Conclusions: Our results demonstrate that thalidomide combined with chemotherapy is mildly effective and safe for treating patients with advanced lung cancer. However, further evaluation of this combination is warranted.

Keywords

Advanced lung cancer;thalidomide;chemotherapy;combined treatment

References

  1. Ansiaux R, Baudelet C, Jordon BF, et al (2005). Thalidomide radiosensitises tumors through early changes in the tumor microenviroment. Clin Cancer Res, 11, 743-50.
  2. Bartlett JB, Dredge K, Dalgleish AG et al (2004). The evolution of thalidomide and its IMiD derivatives as anticancer agents. Nat Rev Cancer, 4, 314-22. https://doi.org/10.1038/nrc1323
  3. Battegay EJ (1995). Angiogenesis: mechanistic insights, neovascular diseases, and therapeutic prospects. J Mol Med (Berl), 73, 333-46.
  4. Carmeliet P, Ferreira V, Breier G, et al (1996). Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature, 380, 435-9. https://doi.org/10.1038/380435a0
  5. Cui L, Liu XX, Jiang Y, et al (2014). Phase II study on dose escalating schedule of paclitaxel concurrent with radiotherapy in treating patients with locally advanced non-small cell lung cancer. Asian Pac J Cancer Prev, 15, 1699-702. https://doi.org/10.7314/APJCP.2014.15.4.1699
  6. D'Amato RJ, Loughnan MS, Flynn E, et al (1994). Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA, 91, 4082-5. https://doi.org/10.1073/pnas.91.9.4082
  7. Ferrara N (1999). Molecular and biological properties of vascular endothelial growth factor. J Mol Med, 77, 527-43. https://doi.org/10.1007/s001099900019
  8. Folkman J (1995). Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med, 1, 27-31. https://doi.org/10.1038/nm0195-27
  9. Fujita J, Mestre JR, Zeldis JB, et al (2001). Thalidomide and its analogues inhibit lipopolysaccharide-mediated induction of -2. Clin Cancer Res, 7, 3349-55.
  10. Geitz H, Handt S, Zwingenberger K (1996). Thalidomide selectively modulates the density of cell surface molecules involved in the adhesion cascade. Immunopharmacology, 31, 213-21. https://doi.org/10.1016/0162-3109(95)00050-X
  11. Gerber HP, Hillan KJ, Ryan AM, et al (1999). VEGF is required for growth and survival in neonatal mice. Development, 126, 1149-59.
  12. Govindan R, Page N , Morgensztern D, et al (2006). Changing epidemiology of small-cell lung cancer in the United States over the last 30years:analysisoftheSurveillance, Epidemiologic, and End Results database. J Clin Oncol, 24, 4539-44. https://doi.org/10.1200/JCO.2005.04.4859
  13. Hanahan D, Weinberg RA (2000).The hallmarks of cancer. Cell, 100, 57-70. https://doi.org/10.1016/S0092-8674(00)81683-9
  14. Haslett PA, Corral LG, Albert M, et al (1998). Thalidomide costimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+ subset. J Exp Med, 187, 1885-92. https://doi.org/10.1084/jem.187.11.1885
  15. Huang XE, Wang L, Ji ZQ, et al (2015). Safety of Lienal Polypeptide Injection Combined with Chemotherapy in Treating Patients with Advanced Cancer. Asian Pac J Cancer Prev, 16, 7837-41. https://doi.org/10.7314/APJCP.2015.16.17.7837
  16. Huang XE, Tian GY, Cao J, et al (2014). Pemetrexed as a component of first-, second- and third- line chemotherapy in treating patients with metastatic lung adenocarcinoma. Asian Pac J Cancer Prev, 14, 6663-7.
  17. Jain RK (2001) .Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med, 7, 987-9. https://doi.org/10.1038/nm0901-987
  18. Jain RK (2005). Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science, 307, 58-62. https://doi.org/10.1126/science.1104819
  19. Jemal A, MurrayT, WardE, et al (2005). Cancer statistics. CA Cancer J Clin, 55, 10-30. https://doi.org/10.3322/canjclin.55.1.10
  20. Ji ZQ, Huang XE, Wu XY, et al (2014). Safety of Brucea javanica and cantharidin combined with chemotherapy for treatment of NSCLC patients. Asian Pac J Cancer Prev, 15, 8603-5. https://doi.org/10.7314/APJCP.2014.15.20.8603
  21. Jin SH, Kim TI, Han DS, et al (2002). Thalidomide suppresses the interleukin 1beta-induced NFkappaB signaling pathway in colon cancer cells. Ann NY Acad Sci, 973, 414-8. https://doi.org/10.1111/j.1749-6632.2002.tb04674.x
  22. Keifer JA, Guttridge DC, Ashburner BP, et al (2001). Inhibition of NF-kappa B activity by thalidomidethrough suppression of IkappaB kinase activity. J Biol Chem, 276, 22382-7. https://doi.org/10.1074/jbc.M100938200
  23. Li Y, Huang XE (2015). A Pooled Analysis on Crizotinib in Treating Chinese Patients with EML4-ALK Positive Non-small-cell Lung Cancer. Asian Pac J Cancer Prev, 16, 4797-800. https://doi.org/10.7314/APJCP.2015.16.11.4797
  24. Mall JW, Philipp AW, Mall W, Pollmann C (2002). Long-term survival of a patient with small-cell lung cancer :SCLC: following treatment with thalidomide and combination chemotherapy. Angiogenesis, 5, 11-3. https://doi.org/10.1023/A:1021546630577
  25. Prat A, Casado E, Cortes J (2007). New approaches in angiogenic targeting for colorectal cancer. World J Gastroenterol, 13, 5857-66. https://doi.org/10.3748/wjg.v13.i44.5857
  26. Plate KH, Breier G, Weich HA, et al (1992). Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature, 359, 845-8. https://doi.org/10.1038/359845a0
  27. Segers J, Fazio VD , Ansiaux R, et al (2006). Potentiation of cyclophosphamide chemotherapy using the anti-angiogenic agent thalidomide:importance of optimal scheduling to exploit the 'normalization 'window of the tumor vasculature. Cancer Lett, 244, 129-35. https://doi.org/10.1016/j.canlet.2005.12.017
  28. Shi B, Zhang XB, Xu J, et al (2015). Systematic Analysis of Icotinib Treatment for Patients with Non-Small Cell Lung Cancer. Asian Pac J Cancer Prev, 16, 5521-4. https://doi.org/10.7314/APJCP.2015.16.13.5521
  29. Shweiki D, Itin A, Soffer D, et al (1992). Vascular endothelial growth factor induced by hypoxia may mediate hypoxiainitiated angiogenesis. Nature, 359, 843-5. https://doi.org/10.1038/359843a0
  30. Vasvari GP, Dyckhoff G, Kashfi F, et al (2007). Combination of thalidomide and cisplatin in an head and neck squamous cell carcinomas model results in an enhanced antiangiogenic activity in vitro and in vivo. Int J Cancer, 121, 1697-704. https://doi.org/10.1002/ijc.22867
  31. Veikkola T, Karkkainen M, Claesson-Welsh L, et al (2000). Regulation of angiogenesis via vascular endothelial growth 7870 Asian Pacific Journal of Cancer Prevention, Vol 16, 2015 factor receptors. Cancer Res, 60, 203-12.
  32. Wu XY, Huang XE (2015). Screening for patients with non-small cell lung cancer who could survive long term chemotherapy. Asian Pac J Cancer Prev, 16, 647-52. https://doi.org/10.7314/APJCP.2015.16.2.647