DOI QR코드

DOI QR Code

Thalidomide Combined with Chemotherapy in Treating Patients with Advanced Colorectal Cancer

  • Huang, Xin-En (Department of Chemotherapy, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research) ;
  • Yan, Xiao-Chun (Department of Medical Oncology, Huai An Cancer Hospital) ;
  • Wang, Lin (Department of Chemotherapy, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research) ;
  • Ji, Zhu-Qing (Department of Chemotherapy, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research) ;
  • Li, Li (Department of Chemotherapy, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research) ;
  • Liu, Meng-Yan (Department of Chemotherapy, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research) ;
  • Qian, Ting (Department of Chemotherapy, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research) ;
  • Shen, Hui-Ling (Zhenjiang First People's Hospital) ;
  • Gu, Han-Gang (Jisngsu University Hospital) ;
  • Liu, Yong (Xu Zhou Central Hospital) ;
  • Gu, Ming (Yan Cheng Third Hospital) ;
  • Deng, Li-Chun (Jiang Yin People's Hospital)
  • Published : 2015.12.03

Abstract

Objective: To assess the safety and effectiveness of thalidomide (produced by CHANGZHOU PHARMACEUTICAL FACTORY CO.LTD) combined with chemotherapy in treating patients with advanced colorectal cancer. Method: A consecutive cohort of pretreated patients with advanced colorectal cancer were treated with thalidomide combined with chemotherapy. And chemotherapy for patients with advanced colorectal cancer were administered according to the condition of patients. Thalidomide was orally administered at a dosage of 50mg/day to 150mg/day before sleeping for at least 14 days. After at least 14 days of treatment, safety and side effects were evaluated. Results: There were 12 female and 3 male patients with advanced cancer recruited into this study, including 9 patients with colon, 6 patients with rectal cancer. The median age of patients was 57(41-82) years. Partial response was observed in 2 patients (2/15), and stable disease in 3 patients(3/15). Incidences of Grade 1 to 2 myelosuppression was observed in 1/15 patients, and Grade 1 to 2 elevation of hepatic enzyme was recorded in 1/15 patients. Adverse effects on the gastrointestinal tract were documented in 1/15 patients, and were Grade 1. No Grade 3-4 toxicities were diagnosed. No treatment related death was found. Conclusions: Thalidomide combined with chemotherapy was safe and mildly effective in treating patients with advanced colorectal cancer. However, further study should be conducted to clarify the effectiveness of this combination.

Keywords

Thalidomide;chemotherapy;advanced colorectal cancer

References

  1. 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
  2. Battegay EJ (1995). Angiogenesis: mechanistic insights, neovascular diseases, and therapeutic prospects. J Mol Med, 73, 333-46.
  3. 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
  4. 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
  5. Ferlay J, Shin HR, Bray F, et al ( 2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 127, 2893-917. https://doi.org/10.1002/ijc.25516
  6. Ferrara N (1999). Molecular and biological properties of vascular endothelial growth factor. J Mol Med, 77, 527-43. https://doi.org/10.1007/s001099900019
  7. Findlay M, Van Cutsem E, KochaW, et al (1997). A randomized phase II study of capecitabine in patients with advanced colorectal cancer. Proc Am Soc Clin Oncol, 16, 227a (Abstr).
  8. Fine HA, Wen PY, Maher EA, et al (2003). Phase II trial of thalidomide and carmustine for patients with recurrent highgrade gliomas. J Clin Oncol, 21, 2299-304. https://doi.org/10.1200/JCO.2003.08.045
  9. Folkman J (1995). Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med, 1, 27-31. https://doi.org/10.1038/nm0195-27
  10. Folkman J (1995). Seminars in Medicine of the Beth Israel Hospital, Boston. Clinical applications of research on angiogenesis. N Engl J Med, 333, 1757-63. https://doi.org/10.1056/NEJM199512283332608
  11. Fujita J, Mestre JR, Zeldis JB, et al (2001). Thalidomide and its analogues inhibit lipopolysaccharide-mediated induction of cyclooxygenase-2. Clin Cancer Res, 7, 3349-55.
  12. 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
  13. Gerber HP, Hillan KJ, Ryan AM, et al (1999). VEGF is required for growth and survival in neonatal mice. Development, 126, 1149-59.
  14. Govindarajan R (2002). Irinotecan/thalidomide in metastatic colorectal cancer. Oncology (Huntingt), 16, 23-6.
  15. 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, 1885-1892. https://doi.org/10.1084/jem.187.11.1885
  16. Jemal A, Bray F, CenterMMet al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  17. 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
  18. Keifer JA, Guttridge DC, Ashburner BP, et al (2001). Inhibition of NF-kappa B activity by thalidomide through suppression of IkappaB kinase activity. J Biol Chem, 276, 22382-7. https://doi.org/10.1074/jbc.M100938200
  19. Lago LD, Richter MF, Cancela AI, et al ( 2003). Phase II trial and pharmacokinetic study of thalidomide in patients with metastatic colorectal cancer. Invest New Drugs, 21, 359-66. https://doi.org/10.1023/A:1025485031112
  20. Nogue M, Segui MA, Batiste E et al (1996). Phase II study of oral Tegafur (TF) and low-dose oral leucovorin in advanced colorectal cancer. Proc Am Soc Clin Oncol, 15, 200 (Abstr).
  21. 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
  22. 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
  23. Rajkumar SV, Witzig TE (2000). A review of angiogenesis and antiangiogenic therapy with thalidomide in multiple myeloma. Cancer Treat Rev, 26, 351-62. https://doi.org/10.1053/ctrv.2000.0188
  24. 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
  25. Veikkola T, Karkkainen M, Claesson-Welsh L, et al (2000). Regulation of angiogenesis via vascular endothelial growth factor receptors. Cancer Res, 60, 203-12,
  26. Yang X, Hu Z, Chan SY, et al (2005). Simultaneous determination of the lactone and carboxylate forms of irinotecan (CPT-11) and its active metabolite SN-38 by high-performance liquid chromatography: application to plasma pharmacokinetic studies in the rat. J Chromatogr B Anal Technol Biomed Life Sci, 821, 221-8. https://doi.org/10.1016/j.jchromb.2005.05.010

Cited by

  1. Safety and Efficacy of a Mouth-Rinse with Granulocyte Colony Stimulating Factor in Patients with Chemotherapy-Induced Oral Mucositis vol.17, pp.1, 2016, https://doi.org/10.7314/APJCP.2016.17.1.413
  2. A Clinical Study on Juheli (Recombinant Human Interleukin - 11) in the Second Prevention of Chemotherapy Induced Thrombocytopenia vol.17, pp.2, 2016, https://doi.org/10.7314/APJCP.2016.17.2.485
  3. Effect of Peripheral Blood CD4 + CD25 + Regulatory T Cell on Postoperative Immunotherapy for Patients with Renal Carcinoma vol.17, pp.4, 2016, https://doi.org/10.7314/APJCP.2016.17.4.2027
  4. Antiangiogenic therapy for primitive neuroectodermal tumor with thalidomide vol.96, pp.51, 2017, https://doi.org/10.1097/MD.0000000000009272