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Pemetrexed and cisplatin in patients with advanced gastric cancer: a Korean cancer study group multicenter phase II study

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Abstract

Background

Pemetrexed is a multitargeted antifolate enzyme inhibitor, which has activity against a variety of tumors, including advanced gastric cancer (AGC). The aim of this study was to assess efficacy and safety of pemetrexed plus cisplatin (PemCis) combination in the treatment of AGC in Korean patients.

Patients and methods

This was a multicenter, single arm, open label study. Patients with no prior palliative chemotherapy received pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 day 1, every 3 weeks plus folic acid and vitamin B12 supplementation. Response rate was assessed according to response evaluation criteria in solid tumors (RECIST) criteria.

Results

Of the 50 patients evaluable for efficacy, 13 had partial response for an overall response rate of 26% (95% CI, 14.6–40.3%) and 15 (30%) had stable disease. Median time to progression was 2.8 months (95%CI, 2.2–4.4 months), and median overall survival was 6.6 months (95% CI, 4.8–10.4 months). Of the 51 patients evaluable for safety, the most frequent NCI-CTC grade 3/4 toxicities were neutropenia in 49% of patients (25% of cycles) and anorexia in 10% of patients (4% of cycles).

Conclusion

PemCis has a modest activity and acceptable toxicity profile in patients with AGC. Clinical trials with different combinations and dose regimens are, therefore, warranted.

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References

  1. Kamangar F, Dores GM, Anderson WF (2006) Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 24:2137–2150

    Article  PubMed  Google Scholar 

  2. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108

    Article  PubMed  Google Scholar 

  3. Parkin DM, Pisani P, Ferlay J (1999) Estimates of the worldwide incidence of twenty-five major cancers in 1990. Int J Cancer 80:827–841

    Article  PubMed  CAS  Google Scholar 

  4. Pisani P, Parkin DM, Bray FI, Ferlay J (1999) Estimates of the worldwide mortality from twenty-five major cancers in 1990. Int J Cancer 83:18–29

    Article  PubMed  CAS  Google Scholar 

  5. Bae JM, Won YJ, Jung KW, Park J-G (2002) Annual report of the Korea Central cancer Registry program 2000: based on registered data from 131 hospitals. Cancer Res Treat 34:77–83

    Google Scholar 

  6. Swan R, Miner TJ (2006) Current role of surgical therapy in gastric cancer. World J Gastroenterol 12:372–379

    PubMed  Google Scholar 

  7. Wils JA, Klein HO, Wagener DJ et al (1991) Sequential high-dose methotrexate and fluorouracil combined with doxorubicin—a step ahead in the treatment of advanced gastric cancer: a trial of the European organization for research and treatment of cancer gastrointestinal tract cooperative group. J Clin Oncol 9:827–831

    PubMed  CAS  Google Scholar 

  8. Vanhoefer U, Rougier P, Wilke H, Ducreux MP, Lacave AJ, Van Cutsem E et al (2000) Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: a trial of the European organization for research and treatment of cancer gastrointestinal tract cancer cooperative group. J Clin Oncol 18:2648–2657

    PubMed  CAS  Google Scholar 

  9. Webb A, Cunningham D, Scarffe JH, Harper P, Norman A, Joffe JK et al (1997) Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol 15(1):261–267

    PubMed  CAS  Google Scholar 

  10. Kim NK, Kim NK, Park YS, Heo DS, Suh C, Kim SY et al (1993) A phase III randomized study of 5-fluorouracil and cisplatin versus 5-fluorouracil, doxorubicin, and mitomycin C versus 5-fluorouracil alone in the treatment of advanced gastric cancer. Cancer 71(12):3813–3818

    Article  PubMed  CAS  Google Scholar 

  11. Kohne CH, Wils JA, Wilke HJ (2000) Developments in the treatment of gastric cancer in Europe. Oncology (Williston Park) 14:22–25

    CAS  Google Scholar 

  12. Fuchs CS (1997) Chemotherapy for advanced gastric cancer: where do we stand? J Clin Oncol 15:3299–3300

    PubMed  CAS  Google Scholar 

  13. Shih C, Habeck LL, Mendelsohn LG et al (1998) Multiple folate enzyme inhibition: mechanism of a novel pyrrolopyrimidine-based antifolate LY231514 (MTA). Adv Enzyme Regul 38:135–152

    Article  PubMed  CAS  Google Scholar 

  14. Rinaldi DA, Kuhn JG, Burris HA, Dorr FA, Rodriguez G, Eckhardt SG et al (1999) A phase I evaluation of multitargeted antifolate (MTA, LY231514), administered every 21 days, utilizing the modified continual reassessment method for dose escalation. Cancer Chemother Pharmacol 44:372–380

    Article  PubMed  CAS  Google Scholar 

  15. Hanauske AR, Chen V, Paoletti P, Niyikiza C (2001) Pemetrexed disodium: a novel antifolate clinically active against multiple solid tumors. Oncologist 6:363–373

    Article  PubMed  CAS  Google Scholar 

  16. Bajetta E, Celio L, Buzzoni R, Ferrari L, Marchiano A, Martinetti A et al (2003) Phase II study of pemetrexed disodium (Alimta) administered with oral folic acid in patients with advanced gastric cancer. Ann Oncol 14:1543–1548

    Article  PubMed  CAS  Google Scholar 

  17. Kim JH, Lee KW, Jung Y, Kim TY, Ham HS, Jong HS et al (2005) Cytotoxic effects of pemetrexed in gastric cancer cells. Cancer Sci 96:365–371

    Article  PubMed  CAS  Google Scholar 

  18. Teicher BA, Alvarez E, Liu P, Lu K, Menon K, Dempsey J et al (1999) MTA (LY231514) in combination treatment regimens using human tumor xenografts and the EMT-6 murine mammary carcinoma. Semin Oncol 26:55–62

    PubMed  CAS  Google Scholar 

  19. Teicher BA, Chen V, Shih C, Menon K, Forier PA, Phares VG et al (2000) Treatment regimens including the multitargeted antifolate LY231514 in human tumor xenografts. Clin Cancer Res 6:1016–1023

    PubMed  CAS  Google Scholar 

  20. Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P et al (2003) Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 21(14):2636–2644

    Article  PubMed  CAS  Google Scholar 

  21. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216

    Article  PubMed  CAS  Google Scholar 

  22. Ajani JA (2005) Evolving chemotherapy for advanced gastric cancer. Oncologist 10(Suppl 3):49–58

    Article  PubMed  CAS  Google Scholar 

  23. Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A, Fleig WE et al (2006) Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol 24:2903–2909

    Article  PubMed  CAS  Google Scholar 

  24. Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenia M, Boni C et al (2006) Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol 24:4991–4997

    Article  PubMed  CAS  Google Scholar 

  25. Bang YJ, Kang WK, Kang YK, Kim HC, Jacques C, Zuber E et al (2002) Docetaxel 75 mg/m(2) is active and well tolerated in patients with metastatic or recurrent gastric cancer: a phase II trial. Jpn J Clin Oncol 32:248–254

    Article  PubMed  Google Scholar 

  26. Kim YH, Sohn SK, Song HS, Kwon KY, Do YR, Lee KH et al (2007) Multicenter phase II study of weekly paclitaxel plus cisplatin combination chemotherapy in patients with advanced gastric cancer. Cancer Chemother Pharmacol (Epub ahead of print)

  27. Kim TW, Kang YK, Ahn JH, Chang HM, Yook JH, Oh ST et al (2002) Phase II study of capecitabine plus cisplatin as first-line chemotherapy in advanced gastric cancer. Ann Oncol 13:1893–1898

    Article  PubMed  CAS  Google Scholar 

  28. Baek JH, Kim JG, Sohn SK, Kim DH, Lee KB, Song HS et al (2005) Biweekly irinotecan and cisplatin as second-line chemotherapy in pretreated patients with advanced gastric cancer: a multicenter phase II study. Korean Med Sci 20:966–970

    Article  CAS  Google Scholar 

  29. Kang Y, Kang KW, Shin DB et al (2006) Randomized phase III trial of capecitabine/cisplatin (XP) vs. continuous infusion of 5-FU/cisplatin (FP) as first-line therapy in patients (pts) with advanced gastric cancer (AGC): efficacy and safety results. J Clin Oncol 24(suppl 20):18s abstr LBA4018

    Google Scholar 

  30. Cunningham D, Rao S, Starling N et al (2006) Randomised multicentre phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric (OG) cancer: the REAL 2 trial. J Clin Oncol 24(Suppl 20):18s abstr LBA4017

    Google Scholar 

  31. Calvert H (2002) Folate status and the safety profile of antifolates. Semin Oncol 29:3–7

    Article  PubMed  CAS  Google Scholar 

  32. Niyikiza C, Hanauske AR, Rusthoven JJ, Calvert AH, Allen R, Paoletti P et al (2002) Pemetrexed safety and dosing strategy. Semin Oncol 29:24–29

    PubMed  Google Scholar 

  33. Hammond LA, Forero L, Beeram M, Forouzesh B, De Bono J, Tolcher A, et al (2003) Phase I study of pemetrexed (LY231514) with vitamin supplementation in patients with locally advanced or metastatic cancer. Proc Am Soc Clin Oncol 22:133 (abstr 532)

    Google Scholar 

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Acknowledgments

This study was funded by Eli Lilly and Company (Study KCSG 03-06-25; H3E-KL-JMFK).

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Authors and Affiliations

  1. Department of Internal Medicine, Korea University Anam Hospital, Seoul, Republic of Korea

    Yeul Hong Kim & Sang Won Shin

  2. Department of Internal Medicine, Yonsei University Severance Hospital, Seoul, Republic of Korea

    Hyun Cheol Chung

  3. Department of Internal Medicine, Samsung Medical Center, Seoul, Republic of Korea

    Won Ki Kang

  4. Center for Gastric Cancer, National Cancer Center, Goyang, Gyeonggi, Republic of Korea

    Sook Ryun Park

  5. Department of Internal Medicine, Inha University Hospital, Inchon, Republic of Korea

    Chul Soo Kim

  6. Department of Internal Medicine, Seoul National University Hospital, 28 Yeongeon-dong, Jongno-gu, Seoul, 110-744, Republic of Korea

    Tae-Yue Kim & Yung-Jue Bang

  7. Clinical Trial Center, Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea

    Byung-Joo Park

  8. Lilly Korea, Seoul, Republic of Korea

    Soo Jin Cha

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  1. Yeul Hong Kim
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Correspondence to Yung-Jue Bang.

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Kim, Y.H., Chung, H.C., Kang, W.K. et al. Pemetrexed and cisplatin in patients with advanced gastric cancer: a Korean cancer study group multicenter phase II study. Cancer Chemother Pharmacol 62, 263–270 (2008). https://doi.org/10.1007/s00280-007-0600-y

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  • DOI: https://doi.org/10.1007/s00280-007-0600-y

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