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A phase I combination chemotherapy study of biweekly paclitaxel and S-1 administration in patients with advanced gastric cancer

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Abstract

The aim of the current study was to determine the maximum tolerated dose (MTD) and the dose limiting toxicity (DLT) of a combination of paclitaxel and S-1 in patients with advanced gastric cancer. Fifteen patients were enrolled. The dose for S-1 was set at 80 mg/m2/day (days 1–14), while the dose for paclitaxel increased by 10 mg/m2 for every three patients, with a starting dose of 100 mg/m2 and was given biweekly on day 1 and 15. There was no severe toxicity (grade 4) recorded in patients receiving up to 120 mg/m2 of paclitaxel. Leukopenia/neutrophilia with grade 1 to 3 occurred in six patients up to level 3. At 130 mg/m2 of paclitaxel, grade 4 leukocytopenia and neutropenia events and grade 3 diarrhea developed in one out of three patients. One patient in another group of three patients that were enrolled at level 3, developed grade 4 granulocytopenia with fever (a body temperature higher than 38°C) and grade 3 leukocytopenia. Eight patients, out of a total of 15, showed a partial response, resulting in an objective response rate of 53%. Five patients received gastrectomy. Median survival time was 428 days and the 1 year survival rate was 53%. Biweekly paclitaxel/S-1 combination chemotherapy could be safely used for the treatment of advanced gastric cancer. The recommended doses for a phase II study with paclitaxel and S-1 are 120 mg/m2 and 80 mg/m2, respectively.

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References

  1. Hasham-Jiwa N, Kasakura Y, Ajani JA (2002) Brief review of advances in the treatment of gastric carcinoma in North America and Europe, 1995–2001. Int J Clin Oncol 7:219–224

    Article  PubMed  CAS  Google Scholar 

  2. Rowinsky EK, Cazenave LA, Donchower RC (1990) Taxol: a novel investigational anticrotubule agent. J Natl Cancer Inst 82:1247–1259

    Article  PubMed  CAS  Google Scholar 

  3. Chang YF, Li LL, Wu CW, Liu TY, Lui WY, P’eng FK, Chi CW (1996) Paclitaxel-induced apoptosis in human gastric carcinoma cell lines. Cancer 77:14–18

    Article  PubMed  CAS  Google Scholar 

  4. Ajani JA, Fairweather J, Dumas P, Patt YZ, Pazdur R, Mansfield PF (1998) Phase II study of Taxol in patients with untreated metastatic gastric carcinoma. Cancer J Sci Am 4:269–274

    PubMed  CAS  Google Scholar 

  5. Kano Y, Akutsu M, Tsunoda S, Ando J, Matsui J, Suzuki K, Ikeda T, Inoue Y, Adachi K (1996) Schedule-dependent interaction between paclitaxel and 5-fluorouracil in human carcinoma cell lines in vitro. Br J Cancer 74:704–710

    PubMed  CAS  Google Scholar 

  6. Schipper DL, Wagener DJT (1996) Chemotherapy of gastric cancer. Anticancer Drugs 7:137–149

    Article  PubMed  CAS  Google Scholar 

  7. Seidman AD, Hudis CA, Albanel J, Tong W, Tepler I, Currie V, Moynahan ME, Theodoulou M, Gollub M, Baselga J, Norton L (1998) Dose-dense therapy with weekly 1-hour paclitaxel infusions in the treatment of metastatic breast cancer. J Clin Oncol 16:3353–3361

    PubMed  CAS  Google Scholar 

  8. Garcia AA, Parimoo D, Dimery I, Rogers M, Jeffers S, Muggia FM (1997) Tolerance of paclitaxel 3-hour infusion with and without granulocyte colony stimulating factor on a biweekly schedule. Semin Oncol 24:S19-62–S19-66

    Google Scholar 

  9. Gelmon KA, Tolcher A, O’Reilly S, Campbell C, Bryce C, Shenkier T, Ragaz J, Ayers D, Nakashima L, Rielly S, Dulude H (1998) A phase I–II study of bi-weekly paclitaxel as first-line treatment in metastatic breast cancer. Ann Oncol 9:1247–1249

    Article  PubMed  CAS  Google Scholar 

  10. Roth AD (2003) Chemotherapy in gastric cancer: a never ending saga. Ann Oncol 14:175–177

    Article  PubMed  CAS  Google Scholar 

  11. Garcia AA, Leichmen CG, Lenz HJ (2001) Phase II trial of outpatient schedule of paclitaxel in patients with previously untreated metastatic, measurable adenocarcinoma of the stomach. Jpn J Clin Oncol 31:275–278

    Article  PubMed  CAS  Google Scholar 

  12. Cascinu S, Ficarelli R, Safi MAA, Graziano F, Catalano G, Cellerino R (1997) A phase I study of paclitaxel and 5-fluorourasil in advanced gastric cancer. Eur J Cancer 10:1699–1702

    Article  Google Scholar 

  13. Shirasaka T, Shimamoto Y, Fukushima M (1993) Inhibition by oxonic acid of gastrointestinal toxicity of 5-fluorouracil without loss of its antitumor activity in rats. Cancer Res 53:4004–4009

    PubMed  CAS  Google Scholar 

  14. Shirasaka T, Shimamoto Y, Ohshimo H, Yamaguchi M, Kato T, Yonekura K, Fukushima M (1996) Development of novel form of an oral 5-fluorouracil derivative (S-1) directed to the potentiation of the tumor selective cytotoxicity of 5-fluorouracil by two biochemical modulators. Anticancer Drugs 7:548–557

    Article  PubMed  CAS  Google Scholar 

  15. Sugimachi K, Maehara Y, Horikoshi N, Shimada Y, Sakata Y, Mitachi Y, Taguchi T (1999) An early phase II study of oral S-1, a newly developed 5-fluorouracil derivative for advanced and recurrent gastrointestinal cancers. The S-1 gastrointestinal cancer study group. Oncology 57:202–210

    Article  PubMed  CAS  Google Scholar 

  16. Sakata Y, Ohtsu A, Horikoshi N, Sugimachi K, Mitachi Y, Taguchi T (1998) Late phase II study of novel oral fluoropyrimidine anticancer drug S-1 (1 M tegafur-0.4 M gimestat-1 M otastat potassium) in advanced gastric cancer patients. Eur J Cancer 34:1715–1720

    Article  PubMed  CAS  Google Scholar 

  17. Koizumi W, Kurihara M, Nakano S, Hasegawa K (2000) Phase II study of S-1, a novel oral derivative of 5-fluorouracil, in advanced gastric cancer. For the S-1 cooperative gastric cancer study group. Oncology 58:191–197

    Article  PubMed  CAS  Google Scholar 

  18. Eisenhauer EA, ten Bokkel Huinink WW, Swenerton KD, Gianni L, Myles J, van der Burg ME, Kerr I, Vermorken JB, Buser K, Colombo N (1994) European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer. High-dose versus low-dose and long versus short infusion. J Clin Oncol 12:2654–2666

    PubMed  CAS  Google Scholar 

  19. Shepherd FA, Latreille J, Crump M, Stewart D, Tomiak E, Eisenhauer E, Fisher B (1996) Phase I study of paxlitaxel (Taxol) and ifosfamide in previously untreated patients with advanced non-small-cell lung cancer. Ann Oncol 7:311–313

    PubMed  CAS  Google Scholar 

  20. Postma TJ, Vermorken JB, Liefting AJ, Pinedo HM, Heimans JJ (1995) Paclitaxel—induced neuropathy. Ann Oncol 5:489–494

    Google Scholar 

  21. Schiller JH, Storer B, Tutsch K, Arzoomanian R, Alberti D, Feierabend C, Spriggs D (1994) Phase I trial of 3-hour paclitaxel with or without granulocyte colony—stimulating factor in patients with advanced cancer. J Clin Oncol 12:241–248

    PubMed  CAS  Google Scholar 

  22. Koizumi W, Tanabe S, Saigenji K, Ohtsu A, Boku N, Nagashima F, Shirao K, Matsumura Y, Gotoh M (2003) Phase I/II study of S-1 combined with cisplatin in patients with advanced gastric cancer. Br J Cancer 89:2207–2212

    Article  PubMed  CAS  Google Scholar 

  23. Iwase H, Shimada M, Tsuzuki T, Horiuchi Y, Kumada S, Haruta J, Yamaguchi T, Sugihara M, Ina K, Kusugami K, Goto S (2005) A phase II multicentric trial of S-1 combined with 24 h-infusion of cisplatin in patients with advanced gastric cancer. Anticancer Res 25:1297–1301

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. First Department of Surgery School of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 8900075, Japan

    Shuichi Hokita, Takashi Aikou, Futoshi Miyazono, Sumiya Ishigami, Kuniaki Aridome, Shigeho Maenohara, Tetsushi Saihara, Kuniaki Suenaga, Hidehiro Nomura, Satoshi Maeda, Hiroyuki Takatori, Hideo Arima, Yasuto Uchikado, Shoji Natsugoe & Sonshin Takao

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  1. Shuichi Hokita
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  2. Takashi Aikou
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  3. Futoshi Miyazono
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  4. Sumiya Ishigami
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  5. Kuniaki Aridome
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  6. Shigeho Maenohara
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  11. Hiroyuki Takatori
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  12. Hideo Arima
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  13. Yasuto Uchikado
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  14. Shoji Natsugoe
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  15. Sonshin Takao
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Correspondence to Shuichi Hokita.

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Hokita, S., Aikou, T., Miyazono, F. et al. A phase I combination chemotherapy study of biweekly paclitaxel and S-1 administration in patients with advanced gastric cancer. Cancer Chemother Pharmacol 57, 736–740 (2006). https://doi.org/10.1007/s00280-005-0122-4

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  • DOI: https://doi.org/10.1007/s00280-005-0122-4

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