The entry of the generic drugs on the market was an impressive development of the pharmaceutical industry and due to their lower prices also a decrease in the cost price for the treatment of patients. The difference in price (sometimes even 50%) between generics and original and different response to therapy sometimes raised serious questions related to their therapeutic equivalence. The scientific community is increasingly interested in this aspect, with studies (in vitro and on patients) demonstrated statistically significant differences in terms of differences generic / original drug. In this context, the aim of our study was to assess the in vitro cytotoxic activity of oxaliplatin (original and generic drug) on DLD-1 cell lines, HT-29, and carboplatin cytotoxic activity (and the reference molecule from Santa Cruz Biotechnology) on cell line A2780. Cell viability was evaluated using the MTT assay.
Regarding the cell line DLD-1, IC50 values of generics was lower than the original after exposure for 24 hours to oxaliplatin but after 48 hours of exposure were not statistically significant differences. HT-29 line has a higher resistance to chemotherapy compared with oxaliplatin, the IC 50 values after 48 hours of exposure are higher than those for the line DLD-1. IC50 values are confirmed by morphological analysis of cells. Regarding carboplatin were not recorded statistically significant differences between the two generic drugs tested.
Although other studies reported differences between generic and branded drugs in terms of hypersensibility reactions, adverse effects and efficacity, we cannot extrapolate our findings to the patients. Further studies on patients are neeeded for a better evaluation of the efficacity of generic vs. original drugs.
1. Bertini I, editor. Bioinorganic chemistry. Mill Valley, Calif: University Science Books; 1994. 611 p.
2. Wheate NJ, Walker S, Craig GE, Oun R. The status of platinum anticancer drugs in the clinic and in clinical trials. Dalton Trans. 2010;39(35):8113. DOI: 10.1039/c0dt00292e
3. Parel M, Ranchon F, Nosbaum A, You B, Vantard N, Schwiertz V, et al. Hypersensitivity to oxaliplatin: clinical features and risk factors. BMC Pharmacol Toxicol. 2014;15(1):1. DOI: 10.1186/2050-6511-15-1
4. Desoize B, Madoulet C. Particular aspects of platinum compounds used at present in cancer treatment. Crit Rev Oncol Hematol. 2002 Jun;42(3):317–25. DOI: 10.1016/S1040-8428(01)00219-0
5. Boulikas T, Vougiouka M. Cisplatin and platinum drugs at the molecular level. (Review). Oncol Rep. 2003 Dec;10(6):1663–82. DOI: 10.3892/or.10.6.1663
7. Gallelli L, Mumoli L, Palleria C, Piro B, Russo E, Vasapollo P, et al. Safety and efficacy of generic drugs with respect to brand formulation. J Pharmacol Pharmacother. 2013;4(5):110. DOI: 10.4103/0976-500X.120972
8. Vetchy D, Vetcha M, Rabiskova M, Gryczova E, Bartosikova L. Comparison in vitro felodipine release rate from the original versus generic product with controlled release of the drug. Med Kaunas Lith. 2007;43(4):326–31.
9. Poirier E, Desbiens C, Poirier B, Hogue J-C, Lemieux J, Doyle C, et al. Comparison of serious adverse events between the original and a generic docetaxel in breast cancer patients. Ann Pharmacother. 2014 Apr;48(4):447–55. DOI: 10.1177/1060028013514941
10. Tange M, Yoshida M, Nakai Y, Uchida T. Comparison between original and generic versions of ceftriaxone sodium preparation for injection: compatibility with calcium-containing product. Chem Pharm Bull (Tokyo). 2012;60(4):429–34. DOI: 10.1248/cpb.60.429
11. Shimatani T, Inoue M, Kuroiwa T, Xu J, Mieno H, Tazuma S. Acid-suppressive effects of generic omeprazole: comparison of three brands of generic omeprazole with original omeprazole. Dig Liver Dis Off J Ital Soc Gastroenterol Ital Assoc Study Liver. 2006 Aug;38(8):554–9. DOI: 10.1016/j.dld.2006.01.032
12. Minzi OMS, Marealle IA, Shekalaghe S, Juma O, Ngaimisi E, Chemba M, et al. Comparison of bioavailability between the most available generic tablet formulation containing artemether and lumefantrine on the Tanzanian market and the innovator’s product. Malar J. 2013;12:174. DOI: 10.1186/1475-2875-12-174
13. Gasser UE, Fischer A, Timmermans JP, Arnet I. Pharmaceutical quality of seven generic Levodopa/Benserazide products compared with original Madopar® / Prolopa®. BMC Pharmacol Toxicol. 2013;14(1):24. DOI: 10.1186/2050-6511-14-24
14. Sittampalam GS, Coussens NP, Nelson H, Arkin M, Auld D, Austin C, et al., editors. Assay Guidance Manual [Internet]. Bethesda (MD): Eli Lilly & Company and the National Center for Advancing Translational Sciences; 2004 [cited 2015 May 1]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK53196/
15. Vanden Berghe T, Grootjans S, Goossens V, Dondelinger Y, Krysko DV, Takahashi N, et al. Determination of apoptotic and necrotic cell death in vitro and in vivo. Methods San Diego Calif. 2013 Jun 1;61(2):117–29. DOI: 10.1016/j.ymeth.2013.02.011
16. Krysko DV, Vanden Berghe T, D’Herde K, Vandenabeele P. Apoptosis and necrosis: Detection, discrimination and phagocytosis. Methods. 2008 Mar;44(3):205–21. DOI: 10.1016/j.ymeth.2007.12.001
17. Chang Y-J, Huang C-Y, Hung C-S, Chen W-Y, Wei P-L. GRP78 mediates the therapeutic efficacy of curcumin on colon cancer. Tumor Biol. 2015 Feb;36(2):633–41. DOI: 10.1007/s13277-014-2640-3
18. Liou J-Y, Aleksic N, Chen S-F, Han T-J, Shyue S-K, Wu KK. Mitochondrial localization of cyclooxygenase-2 and calcium-independent phospholipase A2 in human cancer cells: implication in apoptosis resistance. Exp Cell Res. 2005 May 15;306(1):75–84. DOI: 10.1016/j. yexcr.2005.01.011
19. Sahlberg SH, Spiegelberg D, Glimelius B, Stenerlöw B, Nestor M. Evaluation of Cancer Stem Cell Markers CD133, CD44, CD24: Association with AKT Isoforms and Radiation Resistance in Colon Cancer Cells. Yeudall A, editor. PLoS ONE. 2014 Apr 23;9(4):e94621.