Open Access Peer-reviewed Perspective

Perspectives on chemotherapy-induced toxicities in pancreatic cancer

Article Sidebar

The time line of advancement
Download PDF
Submitted   Dec 4, 2023
Published   Feb 20, 2024
Issue    Vol 5 (2023)
DOI   10.25082/CCR.2023.01.005

Views

381

Downloads

93

Citations

PlumX Metrics

Main Article Content

Henu Kumar Verma corresponding author
Department of Immunopathology, Institute of lungs Health and Immunity, Comprehensive Pneumology Center, 85764 Munich, Germany
Tarun Sahu
Department of Physiology, All India Institute of Medical Science, Raipur 492001, India
LVKS Bhaskar
Department of Zoology, Guru Ghasidas Vishwavidyalaya, Bilaspur 495009, India

Abstract

Despite breakthroughs in screening, identification, and therapy, pancreatic cancer (PC) remains a serious issue in cancer-related mortality. This comprehensive review investigates the long-term and latent effects of chemotherapy in PC, focusing on commonly used medicines such as gemcitabine, docetaxel, irinotecan, nab-paclitaxel, and others. Gemcitabine, a common PC medication, causes a variety of adverse effects, including myelosuppression and weariness. Combination therapy, such as docetaxel and irinotecan, enhance toxicity, resulting in problems such as neutropenia and gastrointestinal difficulties. Significantly, chemotherapy-related complications, such as thrombosis and cardiac difficulties connected to paclitaxel, present serious concerns. Erlotinib, gefitinib, vatalanib, and sunitinib studies show significant side effects. Despite ongoing challenges, determining the causes of the low objective response rate in gemcitabine-refractory patients remains challenging. The study emphasizes the importance of future advances in cancer etiology, arguing for large, straightforward studies examining combination chemotherapies to improve tolerance and minimize chemotherapy-induced sequelae. This overview serves as a thorough guide for physicians, researchers, and policymakers as they navigate the complex terrain of PC chemotherapy, providing significant insights to improve patient care.

Keywords
pencretic cancer, chemoresistance, toxicities

Article Details

How to Cite
Verma, H. K., Sahu, T., & Bhaskar, L. (2024). Perspectives on chemotherapy-induced toxicities in pancreatic cancer. Current Cancer Reports, 5(1), 181-186. https://doi.org/10.25082/CCR.2023.01.005
Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

References

  1. Grossberg AJ, Chu LC, Deig CR, et al. Multidisciplinary standards of care and recent progress in pancreatic ductal adenocarcinoma. CA: A Cancer Journal for Clinicians. 2020, 70(5): 375-403. https://doi.org/10.3322/caac.21626
  2. Miller KD, Siegel RL, Lin CC, et al. Cancer treatment and survivorship statistics, 2016. CA: A Cancer Journal for Clinicians. 2016, 66(4): 271-289. https://doi.org/10.3322/caac.21349
  3. Ferlay J, Colombet M, Soerjomataram I, et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. International Journal of Cancer. 2018, 144(8): 1941-1953. https://doi.org/10.1002/ijc.31937
  4. Shah K, Rawal RM. Genetic and Epigenetic Modulation of Drug Resistance in Cancer: Challenges and Opportunities. Current Drug Metabolism. 2020, 20(14): 1114-1131. https://doi.org/10.2174/1389200221666200103111539
  5. Verma HK, Falco G, Bhaskar LVKS. Molecular Signaling Pathways Involved in Gastric Cancer Chemoresistance. Diagnostics and Therapeutic Advances in GI Malignancies. Published online 2020: 117-134. https://doi.org/10.1007/978-981-15-2017-4_8
  6. Zeng, Pöttler, Lan, et al. Chemoresistance in Pancreatic Cancer. International Journal of Molecular Sciences. 2019, 20(18): 4504. https://doi.org/10.3390/ijms20184504
  7. Lee HS, Park SW. Systemic Chemotherapy in Advanced Pancreatic Cancer. Gut and Liver. 2016, 10(3). https://doi.org/10.5009/gnl15465
  8. Min YJ, Joo KR, Park NH, et al. Gemcitabine Therapy in Patients with Advanced Pancreatic Cancer. The Korean Journal of Internal Medicine. 2002, 17(4): 259-262. https://doi.org/10.3904/kjim.2002.17.4.259
  9. Louvet C, Labianca R, Hammel P, et al. Gemcitabine in Combination With Oxaliplatin Compared With Gemcitabine Alone in Locally Advanced or Metastatic Pancreatic Cancer: Results of a GERCOR and GISCAD Phase III Trial. Journal of Clinical Oncology. 2005, 23(15): 3509-3516. https://doi.org/10.1200/jco.2005.06.023
  10. Lee MG, Lee SH, Lee SJ, et al. 5-Fluorouracil/Leucovorin Combined with Irinotecan and Oxaliplatin (FOLFIRINOX) as Second-Line Chemotherapy in Patients with Advanced Pancreatic Cancer Who Have Progressed on Gemcitabine-Based Therapy. Chemotherapy. 2013, 59(4): 273-279. https://doi.org/10.1159/000356158
  11. You MS, Ryu JK, Choi YH, et al. Efficacy of Nab-Paclitaxel Plus Gemcitabine and Prognostic Value of Peripheral Neuropathy in Patients with Metastatic Pancreatic Cancer. Gut and Liver. 2018, 12(6): 728-735. https://doi.org/10.5009/gnl18220
  12. Ko A. Erlotinib in the treatment of advanced pancreatic cancer. Biologics: Targets & Therapy. Published online March 2008: 83. https://doi.org/10.2147/btt.s1832
  13. Siddiqui NS, Godara A, Byrne MM, et al. Capecitabine for the treatment of pancreatic cancer. Expert Opinion on Pharmacotherapy. 2019, 20(4): 399-409. https://doi.org/10.1080/14656566.2018.1560422
  14. Ko AH, Dito E, Schillinger B, et al. Excess Toxicity Associated with Docetaxel and Irinotecan in Patients with Metastatic, Gemcitabine-Refractory Pancreatic Cancer: Results of a Phase II Study. Cancer Investigation. 2008, 26(1): 47-52. https://doi.org/10.1080/07357900701681483
  15. ZHANG DX, DAI YD, YUAN SX, et al. Prognostic factors in patients with pancreatic cancer. Experimental and Therapeutic Medicine. 2011, 3(3): 423-432. https://doi.org/10.3892/etm.2011.412
  16. Von Hoff DD, Ramanathan RK, Borad MJ, et al. Gemcitabine Plus nab-Paclitaxel Is an Active Regimen in Patients With Advanced Pancreatic Cancer: A Phase I/II Trial. Journal of Clinical Oncology. 2011, 29(34): 4548-4554. https://doi.org/10.1200/jco.2011.36.5742
  17. John P, Butler H, Saif MW. Congestive heart failure secondary to gemcitabine nab-paclitaxel in patients with pancreatic cancer. Anticancer Research. 2014, 34(12): 7267-7270.
  18. Syrigos KN, Michalaki B, Alevyzaki F, et al. A phase-II study of liposomal doxorubicin and docetaxel in patients with advanced pancreatic cancer. Anticancer research. 2002, 22(6B): 3583-3588.
  19. Ulrich-Pur H, Raderer M, Verena Kornek G, et al. Irinotecan plus raltitrexed vs raltitrexed alone in patients with gemcitabine-pretreated advanced pancreatic adenocarcinoma. British Journal of Cancer. 2003, 88(8): 1180-1184. https://doi.org/10.1038/sj.bjc.6600883
  20. Carvajal RD, Tse A, Shah MA, et al. A Phase II Study of Flavopiridol (Alvocidib) in Combination with Docetaxel in Refractory, Metastatic Pancreatic Cancer. Pancreatology. 2009, 9(4): 404-409. https://doi.org/10.1159/000187135
  21. Boeck S, Weigang-Köhler K, Fuchs M, et al. Second-line chemotherapy with pemetrexed after gemcitabine failure in patients with advanced pancreatic cancer: a multicenter phase II trial. Annals of Oncology. 2007, 18(4): 745-751. https://doi.org/10.1093/annonc/mdl463
  22. Stathopoulos G, Boulikas T, Vougiouka M, et al. Liposomal cisplatin combined with gemcitabine in pretreated advanced pancreatic cancer patients: A phase I-II study. Oncology Reports. Published online May 1, 2006. https://doi.org/10.3892/or.15.5.1201
  23. Tschoep KE, Boeck S, Berger F, et al. Regional hyperthermia (RHT) combined with gemcitabine (GEM) + cisplatin (CIS) in patients with GEM-refractory advanced pancreatic cancer: Results of the ESHO phase II trial. Journal of Clinical Oncology. 2008, 26(15$_$suppl): 4635-4635. https://doi.org/10.1200/jco.2008.26.15_suppl.4635
  24. Verma HK, Kampalli PK, Lakkakula S, et al. A Retrospective Look at Anti-EGFR Agents in Pancreatic Cancer Therapy. Current Drug Metabolism. 2020, 20(12): 958-966. https://doi.org/10.2174/1389200220666191122104955
  25. Lakkakula BVKS, Farran B, Lakkakula S, et al. Small molecule tyrosine kinase inhibitors and pancreatic cancer—Trials and troubles. Seminars in Cancer Biology. 2019, 56: 149-167. https://doi.org/10.1016/j.semcancer.2018.09.011
  26. Kulke MH, Blaszkowsky LS, Ryan DP, et al. Capecitabine Plus Erlotinib in Gemcitabine-Refractory Advanced Pancreatic Cancer. Journal of Clinical Oncology. 2007, 25(30): 4787-4792. https://doi.org/10.1200/jco.2007.11.8521
  27. Ignatiadis M, Polyzos A, Stathopoulos GP, et al. A Multicenter Phase II Study of Docetaxel in Combination with Gefitinib in Gemcitabine-Pretreated Patients with Advanced/Metastatic Pancreatic Cancer. Oncology. 2006, 71(3-4): 159-163. https://doi.org/10.1159/000106064
  28. Brell JM, Matin K, Evans T, et al. Phase II Study of Docetaxel and Gefitinib as Second-Line Therapy in Gemcitabine Pretreated Patients with Advanced Pancreatic Cancer. Oncology. 2009, 76(4): 270-274. https://doi.org/10.1159/000206141
  29. Dragovich T, Laheru D, Dayyani F, et al. Phase II trial of vatalanib in patients with advanced or metastatic pancreatic adenocarcinoma after first-line gemcitabine therapy (PCRT O4-001). Cancer Chemotherapy and Pharmacology. 2014, 74(2): 379-387. https://doi.org/10.1007/s00280-014-2499-4
  30. O’Reilly EM, Niedzwiecki D, Hollis DR, et al. A phase II trial of sunitinib (S) in previously-treated pancreas adenocarcinoma (PAC), CALGB 80603. Journal of Clinical Oncology. 2008, 26(15$_$suppl): 4515-4515. https://doi.org/10.1200/jco.2008.26.15_suppl.4515
  31. Adamska A, Domenichini A, Falasca M. Pancreatic Ductal Adenocarcinoma: Current and Evolving Therapies. International Journal of Molecular Sciences. 2017, 18(7): 1338. https://doi.org/10.3390/ijms18071338
  32. Javle MM, Shroff RT, Xiong H, et al. Inhibition of the mammalian target of rapamycin (mTOR) in advanced pancreatic cancer: results of two phase II studies. BMC Cancer. 2010, 10(1). https://doi.org/10.1186/1471-2407-10-368
  33. Kagawa S, Takano S, Yoshitomi H, et al. Akt/mTOR signaling pathway is crucial for gemcitabine resistance induced by Annexin II in pancreatic cancer cells. Journal of Surgical Research. 2012, 178(2): 758-767. https://doi.org/10.1016/j.jss.2012.05.065
  34. Koltai T, Reshkin SJ, Carvalho TMA, et al. Resistance to Gemcitabine in Pancreatic Ductal Adenocarcinoma: A Physiopathologic and Pharmacologic Review. Cancers. 2022, 14(10): 2486. https://doi.org/10.3390/cancers14102486
  35. Turco C, Jary M, Kim S, et al. Gemcitabine-Induced Pulmonary Toxicity: A Case Report of Pulmonary Veno-Occlusive Disease. Clinical Medicine Insights: Oncology. 2015, 9: CMO.S26537. https://doi.org/10.4137/cmo.s26537
  36. Baig J, Shokouh-Amiri M, Chan J, et al. The Spectrum of Pulmonary Toxicity in Pancreatic Cancer Patients Receiving Gemcitabine Combination Chemotherapy. Case Reports in Oncology. 2019, 12(2): 506-512. https://doi.org/10.1159/000500242
  37. Hama Y. Exacerbation of gemcitabine-related pneumonia during radiotherapy for extrapulmonary lesion. International Cancer Conference Journal. 2016, 6(1): 35-37. https://doi.org/10.1007/s13691-016-0267-5
  38. Liu G, Li G, Zhao H. Efficacy and Toxicity of Different Chemotherapy Regimens in the Treatment of Advanced or Metastatic Pancreatic Cancer: A Network Meta‐Analysis. Journal of Cellular Biochemistry. 2017, 119(1): 511-523. https://doi.org/10.1002/jcb.26210
  39. Siegel RL, Miller KD, Wagle NS, et al. Cancer statistics, 2023. CA: A Cancer Journal for Clinicians. 2023, 73(1): 17-48. https://doi.org/10.3322/caac.21763
  40. Hamidi H, Lu M, Chau K, et al. KRAS mutational subtype and copy number predict in vitro response of human pancreatic cancer cell lines to MEK inhibition. British Journal of Cancer. 2014, 111(9): 1788-1801. https://doi.org/10.1038/bjc.2014.475