Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Outcome of Single Agent Generic Gemcitabine in Platinum-Resistant Ovarian Cancer, Fallopian Tube Cancer and Primary Peritoneal Adenocarcinoma

  • Suprasert, Prapaporn (Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University) ;
  • Cheewakriangkrai, Chalong (Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University) ;
  • Manopunya, Manatsawee (Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University)
  • Published : 2012.02.29
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Abstract

Single original gemcitabine is commonly used as salvage treatment in platinum-resistant ovarian cancer, fallopian tube cancer and primary peritoneal adenocarcinoma (PPA) with a satisfactory outcome. However, efficacy data fro this regimen are limited. We therefore conducted a retrospective study to evaluate the outcome of patients who received single-agent generic gemcitabine (GEMITA) after development of clinical platinum resistance. The study period was between May 2008 and December 2010. Gemcitabine was administered intravenously in two different schedules: 1,000 $mg/m^2$ on day 1,8, and 15 every 28 days; and on days 1 and 8 every 21 days with the same dosage. Administration was until disease progression was noted. The response rate was evaluated using the Gynecologic Cancer Intergroup (GCIG) criteria while toxicity was evaluated according to WHO criteria. Sixty-six patients met the inclusion criteria in the study period. Two-thirds of them received gemcitabine as the second and third line regimen. The overall response rate was 12.1%. The median progression free survival and overall survival was 2 and 10 months, respectively. With the total 550 courses of chemotherapy,the patients developed grades 3 and 4 hematologic toxicity as follows: anemia, 1.5%; leukopenia, 13.7%; neutropenia, 27.3%; and thrombocytopenia, 3.0%. In conclusion, single agent generic gemcitabine revealed a modest efficacy in patients with platinum-resistant ovarian cancer, fallopian tube cancer and PPA without serious toxicity.

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References

  1. Distefano M, Ferlini C, De Vincenzo R, et al (2001). Antagonistic effect of the combination gemcitabine/topotecan in ovarian cancer cells. Oncol Res, 12, 335-59. https://doi.org/10.3727/096504001108747783
  2. Hahnvajanawong C, Bhudisawadi V, Namwat N, et al (2011). Comparative in vitro cytotoxicity of the generic and reference products of gemcitabine on various cancer cell lines. Srinagarind Med J, 26, 1-8.
  3. Huang P, Chubb S, Hertel L, et al (1991). Action of 2_,2_-diflurodeoxycytidine on DNA synthesis. Cancer Res, 51, 6110-7.
  4. Heinemann V, Xu YZ, Chubb S, et al (1990). Inhibition of ribonucleotide reduction in CCRF-CEM cells by 2_,2_-difluorodeoxycytidine. Mol Pharmacol, 38, 567-72.
  5. Heinemann V, Hertel LW, Grindey GB, et al (1988). Comparison of the cellular pharmacokinetics and toxicity of 2_,2_-difluorodeoxycytidine and 1-beta-d-arabinofuranosyl cytosine. Cancer Res, 48, 4024-31.
  6. Lorusso D, Di Stefano A, Fanfani F, et al (2006). Role of gemcitabine in ovarian cancer treatment. Ann Oncol, 17, 188-94. https://doi.org/10.1093/annonc/mdj979
  7. Mutch DG, Orlando M, Goss T, et al (2007). Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. J Clin Oncol, 25, 2811-8. https://doi.org/10.1200/JCO.2006.09.6735
  8. Mackey JR, Mani RS, Selner M, et al (1998). Functional nucleoside transporters are required for gemcitabine influx and manifestation of toxicity in cancer cell lines. Cancer Res, 58, 4349-57.
  9. Miller AB, Hoogstraten B, Staquet M,et al (1981). Reporting results of cancer treatment . Cancer, 47, 207-14. https://doi.org/10.1002/1097-0142(19810101)47:1<207::AID-CNCR2820470134>3.0.CO;2-6
  10. Ojeda Gonzalez B, Gonzalez Martin A, Bover Barcelo I, et al (2008). A phase II trial of fixed-dosed rate gemcitabine in platinum-resistant ovarian cancer: a GEICO (Grupo Español de Investigación en Cáncer de Ovario) Trial. Am J Clin Oncol, 31, 481-7. https://doi.org/10.1097/COC.0b013e31816d1c7b
  11. Peters GJ, Bergman AM, Ruiz van Haperen VW, et al (1995). Interaction between cisplatin and gemcitabine in vitro and in vivo. Semin Oncol, 22, 72-9.
  12. Rustin GJ, Vergote I, Eisenhauer E, et al (2011). Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the Gynecological Cancer Intergroup (GCIG). Int J Gynecol Cancer, 21, 419-23. https://doi.org/10.1097/IGC.0b013e3182070f17
  13. Ruiz van Haperen VW, Veerman G, Boven E, et al (1994). Schedule dependence of sensitivity to 29,29-difluorodeoxycytidine- (gemcitabine) in relation to accumulation and retention of its triphosphate in solid tumour cell lines and solid tumours. Biochem Pharmacol, 48, 1327-39. https://doi.org/10.1016/0006-2952(94)90554-1
  14. Ruiz van Haperen VW, Veerman G, Vermorken JB, et al (1993). 2',2'-Diflurodeoxycytidine (gemcitabine) incorporation into RNA and DNA from tumour cell lines. Biochem Pharmacol , 46, 762-6. https://doi.org/10.1016/0006-2952(93)90566-F
  15. Van Moorsel CJ, Peters GJ, Pinedo HM (1997). Gemcitabine: future prospects of single-agent and combination studies. Oncologist, 2, 127-34.
  16. Watanabe Y, Koike E, Nakai H, et al (2008). Phase II study of single-agent gemcitabine in heavily pretreated Japanese patients with recurrent ovarian cancer. Int J Clin Oncol, 13, 345-8. https://doi.org/10.1007/s10147-008-0765-3

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