Skip to main content

Advertisement

SpringerLink
Log in

A phase I study of paclitaxel, cisplatin, and fluorouracil (TCF) for advanced gastric cancer

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

A phase I study of TCF therapy, which consists of paclitaxel (TXL: Taxol®) + cisplatin (CDDP) + 5-fluorouracil (5-FU), in advanced gastric cancer patients was performed to determine the recommended dose (RD) for a phase II study by checking the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of 5-FU above the fixed dose of TXL and CDDP.

Methods

The doses of TXL and CDDP were fixed at 80 and 25 mg/m2, respectively, while that of 5-FU was increased by 100 mg/m2 in each cohort from 300 mg/m2 (level 1) to a maximum of 600 mg/m2 (level 4). One cycle consisted of administration of these agents once per week for 3 weeks, every 4 weeks.

Results

A total of twelve eligible patients were included in this study. At level 1, two of three cases showed grade 3 leukopenia. At level 2, one of three cases showed grade 4 neutropenia (recovered within 3 days), and another one case showed grade 3 neutropenia. At level 3, one of three cases showed grade 3 neutropenia, and at level 4, one of three cases showed grade 4 neutropenia (recovered within 3 days), with grade 3 neutropenia in the other two cases. Even at the highest dose administered, none of the patients showed DLT. Moreover, no non-hematological toxicity judged to be DLT was observed through all levels. Six of the twelve patients had measurable disease, and the overall response rate was 83%.

Conclusions

Although the MTD level was not determined, based on the observed efficacy and the results of other clinical trials, the recommended doses of TXL, CDDP, and 5-FU for the TCF regimen were set as 80, 25, and 600 mg/m2, respectively, and a phase II study to investigate the clinical effectiveness and safety of this regimen has now begun.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ajani JA, Fairweather J, Dumas P (1998) Phase II study of Taxol in patients with advanced gastric carcinoma. Cancer J Sci Am 4:269–274

    PubMed  CAS  Google Scholar 

  2. Ajani JA, Fodor MB, Tjulandin SA (2005) Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or without fluorouracil in patients with untreated, advanced gastric, or gastroesophageal adenocarcinoma. J Clin Oncol 23:5844

    Google Scholar 

  3. Bonomi P, Kim K, Kusler J (1997) Cisplatin/etoposide vs paclitaxel/cisplatin/G-CSF vs paclitaxel/cisplatin in non-small-cell lung cancer. Oncology 11(4 Suppl 3):9–10

    PubMed  CAS  Google Scholar 

  4. Cascinu S, Graziano F, Cardarelli N (1998) Phase II study of paclitaxel in pretreated advanced gastric cancer. Anticancer Drugs 9:307–310

    Article  PubMed  CAS  Google Scholar 

  5. Cullinan SA, Moertel CG, Wieand HS (1994) Controlled evaluation of three drug combination regimens versus fluorouracil alone for the therapy of advanced gastric cancer. North Central Cancer Treatment Group. J Clin Oncol 12:412–416

    PubMed  CAS  Google Scholar 

  6. Glimelius B, Hoffman K, Haglund U (1994) Initial or delayed chemotherapy with best supportive care in advanced gastric cancer. Ann Oncol 5:189–190

    PubMed  CAS  Google Scholar 

  7. Health, Welfare Statistics Association (1999) The movement of population. J Health Welfare Stat 46(suppl):41–72

    Google Scholar 

  8. Honecker F, Kollmannsberger C, Quietzsch D (2002) Phase II study of weekly paclitaxel plus 24-h continuous infusion 5-fluorouracil, folinic acid and 3-weekly cisplatin for the treatment of patients with advanced gastric cancer. Anticancer drugs 13:497–503

    Article  PubMed  CAS  Google Scholar 

  9. Kim NK, Park YS, Heo DS (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 71:3813–3818

    Article  PubMed  CAS  Google Scholar 

  10. Kim YH, Shin SW, Kim BS (1999) Paclitaxel, 5-fluorouracil, and cisplatin combination chemotherapy for the treatment of advanced gastric carcinoma. Cancer 85:295–301

    Article  PubMed  CAS  Google Scholar 

  11. Kunimoto T, Nitta K, Tanaka T (1987) Antitumor activity of 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy-camptothecin, a novel water-soluble derivative of camptothecin, against murine tumors. Cancer Res 47:5944–5947

    PubMed  CAS  Google Scholar 

  12. Lacave AJ, Baron FJ, Anton LM (1991) Combination chemotherapy with cisplatin and 5-fluorouracil 5-day infusion in the therapy of advanced gastric cancer: a phase II trial. Ann Oncol 2:751–754

    PubMed  CAS  Google Scholar 

  13. Loffler TM, Freund W, Lipke J (1996) Schedule- and dose-intensified paclitaxel as weekly 1-hour infusion in pretreated solid tumors: results of a phase I/II trial. Semin Oncol 23(6 Suppl 16):32–34

    PubMed  CAS  Google Scholar 

  14. Longnecker SM, Donehower RC, Cates AE (1987) High-performance liquid chromatographic assay for taxol in human plasma and urine and pharmacokinetics in a phase I trial. Cancer Treat Rep 71:53–59

    PubMed  CAS  Google Scholar 

  15. McGuire WP, Hoskins WJ, Brady MF (1996) Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med 334:1–6

    Article  PubMed  CAS  Google Scholar 

  16. Moertel CG (1975) Clinical management of advanced gastrointestinal cancer. Cancer 36:675–682

    Article  PubMed  CAS  Google Scholar 

  17. Moertel CG, Rubin J, O’Connell MJ (1986) A phase II study of combined 5-fluorouracil, doxorubicin, and cisplatin in the treatment of advanced upper gastrointestinal adenocarcinomas. J Clin Oncol 4:1053–1057

    PubMed  CAS  Google Scholar 

  18. Murad AM, Petroianu A, Guimaraes RC (1999) Phase II trial of the combination of paclitaxel and 5-fluorouracil in the treatment of advanced gastric cancer: a novel, safe, and effective regimen. Am J Clin Oncol 22:580–586

    Article  PubMed  CAS  Google Scholar 

  19. Murad AM, Santiago FF, Petroianu A (1993) Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Cancer 72:37–41

    Article  PubMed  CAS  Google Scholar 

  20. Nagata N, Kobayashi M, Kojima H (2005) Phase I study of paclitaxel and cisplatin for patients with advanced or recurrent gastric cancer. Hepatogastroenterology 52:1905–1910

    PubMed  CAS  Google Scholar 

  21. Ninomiya M, Kondo K, Kojima H (2005) Phase II study of weekly paclitaxel plus 5-fluorouracil in patients with unresectable advanced or recurrent gastric cancer. Proc ASCO 24:4075

    Google Scholar 

  22. Ohtsu A, Shimada Y, Shirao K (2003) Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: The Japan Clinical Oncology Group Study (JCOG9205). J Clin Oncol 21:54–59

    Article  PubMed  CAS  Google Scholar 

  23. Oken MM, Creech RH, Tormey DC (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649–655

    PubMed  CAS  Google Scholar 

  24. Pyrhonen S, Kuitunen T, Nyandoto P (1995) Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer. Br J Cancer 71:587–591

    PubMed  CAS  Google Scholar 

  25. Rosenberg P, Andersson H, Boman K (2002) Randomized trial of single agent paclitaxel given weekly versus every three weeks and with peroral versus intravenous steroid premedication to patients with ovarian cancer previously treated with platinum. Acta Oncol 41:418–424

    Article  PubMed  CAS  Google Scholar 

  26. Rowinsky EK, Donehower RC (1995) Paclitaxel (taxol). N Engl J Med 332:1004–1014

    Article  PubMed  CAS  Google Scholar 

  27. Seidman AD, Hudis CA, Albanel J (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 

  28. Shirasaka T, Shimamato Y, Ohshimo H (1996) Development of a 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 

  29. Therasse P, Arbuck SG, Eisenhauer EA (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 

  30. Torres K, Horwitz SB (1998) Mechanisms of Taxol-induced cell death are concentration dependent. Cancer Res 58:3620–3626

    PubMed  CAS  Google Scholar 

  31. Waters JS, Norman A, Cunningham D (1999) Long-term survival after epirubicin, cisplatin and fluorouracil for gastric cancer: results of a randomized trial. Br J Cancer 80:269–272

    Article  PubMed  CAS  Google Scholar 

  32. Webb A, Cunningham D, Scarffe JH (1997) Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol 15:261–267

    PubMed  CAS  Google Scholar 

  33. Yamada Y, Shirao K, Ohtsu A (2001) Phase II trial of paclitaxel by three-hour infusion for advanced gastric cancer with short premedication for prophylaxis against paclitaxel-associated hypersensitivity reactions. Ann Oncol 12:1133–1137

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Kouseiren Takaoka Hospital, 5-10 Eiraku-cho, Takaoka, Toyama, 933-8555, Japan

    Takuo Hara & Makoto Hirano

  2. Department of General and Cardiothoracic Surgery, Kanazawa University School of Medicine, Kanazawa, Japan

    Kenji Omura

  3. Department of Surgery, Fukui Saiseikai Hospital, Fukui, Japan

    Yasuyuki Asada & Yoshinori Munemoto

  4. Department of Epidemiological and Clinical Research Information Management, Kyoto University Graduate School of Medicine, Kyoto, Japan

    Junichi Sakamoto

Authors
  1. Takuo Hara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kenji Omura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Makoto Hirano
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yasuyuki Asada
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yoshinori Munemoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Junichi Sakamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Takuo Hara.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hara, T., Omura, K., Hirano, M. et al. A phase I study of paclitaxel, cisplatin, and fluorouracil (TCF) for advanced gastric cancer. Cancer Chemother Pharmacol 59, 631–636 (2007). https://doi.org/10.1007/s00280-006-0305-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-006-0305-7

Keywords

Search

Navigation