Download PDF

Gastric Cancer

, Volume 13, Issue 2, pp 101–108 | Cite as

Pilot study of a combination of S-1 and paclitaxel for patients with peritoneal metastasis from gastric cancer

  • Shigeyuki Tamura
  • Hirofumi Miki
  • Kaoru Okada
  • Atsushi Takeno
  • Kumiko Uji
  • Atsuko Yoshida
  • Rei Suzuki
  • Shin Nakahira
  • Chiyomi Egawa
  • Ken Nakata
  • Shu Okamura
  • Keishi Sugimoto
  • Yuichi Takatsuka
Original Article
First Online:
Received:
Accepted:

Abstract

Background

This pilot study was carried out to evaluate the efficacy of chemotherapy for patients with peritoneal dissemination from gastric cancer or positive lavage cytology diagnosed by staging laparoscopy.

Methods

Sixteen patients were enrolled. Paclitaxel was administered at 120 mg/m2 on day 1 and S-1 was administered orally at 80 mg/m2 for 14 consecutive days, followed by a 1-week rest, as one course. After five courses of this therapy, the primary gastric tumors were evaluated and second-look laparoscopy was performed for patients showing partial response or stable disease with clinical benefit.

Results

Partial response or stable disease with clinical benefit was confirmed in seven and five patients, respectively, and these patients underwent second-look laparoscopy. No viable cancer cells were detected on cytopathological investigation during second-look laparoscopy in 9 patients who underwent surgical treatment. The intent-to-treat response rate for gastric tumor was 44% and the rate of disappearance of peritoneal metastasis was 38% (6 cases) at surgery. The median survival time was 555 days. Leucopenia of grade 3 and neutropenia of grade 3 were recognized in two and three patients, respectively.

Conclusion

This chemotherapy regimen may be an acceptable option for patients with peritoneal dissemination. We plan to study this regimen further in gastric cancer patients with peritoneal dissemination.

Key words

Advanced gastric cancer Peritoneal dissemination Combination chemotherapy Paclitaxel S-1 
Download to read the full article text

References

  1. 1.
    Kakeji Y, Maehara Y, Tomoda M, Kabashima A, Ohmori M, Oda S, et al. Long term survival of patients with stage IV gastric cancer. Cancer 1998;82:2307–2311.CrossRefPubMedGoogle Scholar
  2. 2.
    Yonemura Y, Sawa T, Kinoshita K, Matsuki N, Fushida S, Tanaka S, et al. Neoadjuvant chemotherapy for high-grade advanced gastric cancer. World J Surg 1993;17:256–262.CrossRefPubMedGoogle Scholar
  3. 3.
    Hagiwara A, Takahashi T, Kojima O, Sawai K, Yamaguchi T, Yamane T, et al. Prophylaxis with carbon-absorbed mitomycin C against peritoneal recurrence of gastric cancer. Lancet 1992;339:629–631.CrossRefPubMedGoogle Scholar
  4. 4.
    Sakata Y, Ohtsu A, Horikoshi N, Sugimachi K, Mitachi Y, Taguchi T. Late phase II study on novel oral fluoropyrimidine anticancer drug S-1 (IM Tegafur-0.4M Gimestat-1M Otastat Potassium) in advanced gastric cancer patients. Eur J Cancer 1998;34:1715–1720.CrossRefPubMedGoogle Scholar
  5. 5.
    Koizumi W, Kurihara M, Nakano S, Hasegawa K. Phase II study of S-1, a novel oral derivative of 5-fluorouracil, in advanced gastric cancer. Oncology 2000;58:191–197.CrossRefPubMedGoogle Scholar
  6. 6.
    Osugi H, Takada N, Takemura M, Kaseno S, Lee S, Ueno M, et al. Oral fluoropyrimidine anticancer drug TS-1 for gastric cancer patients with peritoneal dissemination. Oncol Rep 2002;9:811–815.PubMedGoogle Scholar
  7. 7.
    Kitamura Y, Hayashi K, Sasagawa T, Oguma H, Takasaki K. Pilot study of S-1 in patients with disseminated gastric cancer. Drugs Exp Clin Res 2003;29:125–130.PubMedGoogle Scholar
  8. 8.
    Koizumi W, Tanabe S, Saigenji T, Ohtsu A, Boku N, Nagashima F, et al. Phase I/II study of S-1 combined with cisplatin in patients with advanced gastric cancer. Br J Cancer 2003;89:2207–2212.CrossRefPubMedGoogle Scholar
  9. 9.
    Yoshida K, Ninomiya M, Takakura N, Hirabayashi N, Takiyama W, Sato Y, et al. Phase II study of docetaxel and S-1 combination therapy for advanced or recurrent gastric cancer. Clin Cancer Res 2006;12:3402–3407.CrossRefPubMedGoogle Scholar
  10. 10.
    Mochiki E, Ohno T, Kamiyama Y, Aihara R, Haga N, Ojima H, et al. Phase I/II study of S-1 combined with paclitaxel in patients with unresectable and/or recurrent advanced gastric cancer. Br J Cancer 2006;95:1642–1747.CrossRefPubMedGoogle Scholar
  11. 11.
    Inokuchi M, Yamashita T, Yamada H, Kojima K, Ichikawa W, Nihei Z, et al. Phase I/II study of S-1 combined with irinotecan for metastatic advanced gastric cancer. Br J Cancer 2006;94:1130–1135.CrossRefPubMedGoogle Scholar
  12. 12.
    Rowinsky EK, Donehower RC, Jones RJ, Tucker RW. Microtubule changes and cytotoxicity in leukemic cell lines treated with taxol. Cancer Res 1988;48:4093–4100.PubMedGoogle Scholar
  13. 13.
    Kobayashi M, Sakamoto J, Namikawa T, Okamoto K, Okabayashi T, Ichikawa K, et al. Pharmacokinetic study of paclitaxel in malignant ascites from advanced gastric cancer patients. World J Gastroenterol 2006;12:1412–1415.PubMedGoogle Scholar
  14. 14.
    Narahara H, Fujitani K, Takiuchi H, Sugimoto N, Inoue K, Uedo N, et al. Phase II study of a combination of S-1 and paclitaxel in patients with unresectable or metastatic gastric cancer. Oncology 2008;74:37–41.CrossRefPubMedGoogle Scholar
  15. 15.
    Kodera Y, Yamamura Y, Shimizu Y, Torii A, Hirai T, Yasui K, et al. Peritoneal wash cytology: prognostic value of positive findings in patients with gastric carcinoma undergoing a potentially curative resection. J Surg Oncol 1999;72:60–65.CrossRefPubMedGoogle Scholar
  16. 16.
    Burke EC, Karpeh MS Jr, Conlon KC, Brennan MF. Peritoneal lavage cytology in gastric cancer: an independent predictor of outcome. Ann Surg Oncol 1998;5:411–415.CrossRefPubMedGoogle Scholar
  17. 17.
    Tamura S, Miki H, Nakata K, Takiuchi D, Okada K, Nakahira S, et al. Intraperitoneal administration of paclitaxel and oral S-1 for patients with peritoneal dissemination and hydronephrosis due to advanced gastric cancer. Gastric Cancer 2007;10:251–255.CrossRefPubMedGoogle Scholar
  18. 18.
    Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma. — 2nd English Edition —. Gastric Cancer 1998;1:10–24.CrossRefPubMedGoogle Scholar
  19. 19.
    Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma. — 2nd English Edition — Response assessment of chemotherapy and radiotherapy for gastric carcinoma: clinical criteria. Gastric Cancer 2001;4:1–8.CrossRefGoogle Scholar
  20. 20.
    Sotiropoulos GC, Kaiser GM, Lang H, Treckmann J, Brokalaki EI, Pottgen C, et al. Staging laparoscopy in gastric cancer. Eur J Med Res 2005;10:88–91.PubMedGoogle Scholar
  21. 21.
    Nakagawa S, Nashimoto A, Yabusaki H. Role of staging laparoscopy with peritoneal lavage cytology in the treatment of locally advanced gastric cancer. Gastric Cancer 2007;10:29–34.CrossRefPubMedGoogle Scholar
  22. 22.
    Oshima T, Yamada R, Hatori S, Kunisaki C, Imada T. Pharmacokinetics of S-1 in patients with peritoneal dissemination of gastric cancer. Oncol Rep 2006;16:361–366.PubMedGoogle Scholar
  23. 23.
    Hosokawa A, Sugiyama T, Ohtsu A, Doi T, Hattori S, Kojima T, et al. Long-term outcomes of patients with metastatic gastric cancer after initial S-1 monotherapy. J Gastroenterol 2007;42:533–538.CrossRefPubMedGoogle Scholar
  24. 24.
    Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, et al. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol 2008;9:215–221.CrossRefPubMedGoogle Scholar
  25. 25.
    Dickinson R, Presgrave P, Levi J, Milliken S, Woods R. Sequential moderate-dose methotrexate and 5-fluorouracil in advanced gastric adenocarcinoma. Cancer Chemother Pharmacol 1989;24:67–68.CrossRefPubMedGoogle Scholar
  26. 26.
    Pérez JE, Lacava JA, Dominguez ME, Rodriguez R, Barbieri MR, Ortiz EH, et al. Biochemical modulation of 5-fluorouracil by methotrexate in patients with advanced gastric carcinoma. Am J Clin Oncol 1998;21:452–457.CrossRefPubMedGoogle Scholar
  27. 27.
    Murakami M, Ota K, Miyazaki T, Niitsu Y, Wakui A, Yokoyama M, et al. Sequential methotrexate-5-fluorouracil (MTX-5-FU) treatment for patients with advanced gastric and colorectal cancer (in Japanese with English abstract). Gan To Kagaku Ryoho 1987;14:2482–2490.PubMedGoogle Scholar
  28. 28.
    Konishi T, Hiraishi M, Mafune K, Miyama T, Hirata T, Mori K, et al. Therapeutic efficacy and toxicity of sequential methotrexate and 5-fluorouracil in gastric cancer. Anticancer Res 1994;14:1277–1280.PubMedGoogle Scholar
  29. 29.
    Tahara M, Ohtsu A, Boku N, Nagashima F, Muto M, Sano Y, et al. Sequential methotrexate and 5-fluorouracil therapy for gastric cancer patients with peritoneal dissemination: a retrospective study. Gastric Cancer 2001;4:212–218.CrossRefPubMedGoogle Scholar
  30. 30.
    Yamao T, Shimada Y, Shirao K, Ohtsu A, Ikeda N, Hyodo I, et al. Phase II study of sequential methotrexate and 5-fluorouracil chemotherapy against peritoneally disseminated gastric cancer with malignant ascites: a report from the Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group, JCOG 9603 Trial. Jpn J Clin Oncol 2004;34:316–322.CrossRefPubMedGoogle Scholar
  31. 31.
    Fushida S, Furui N, Kinami S, Ninomiya I, Fujimura T, Nishimura G, et al. Pharmacologic study of intraperitoneal paclitaxel in gastric cancer patients with peritoneal dissemination (in Japanese with English abstract). Gan To Kagaku Ryoho 2002;29:2164–2167.PubMedGoogle Scholar
  32. 32.
    Yonemura Y, Endou Y, Bando E, Kuno K, Kawamura T, Kimura M, et al. Effect of intraperitoneal administration of docetaxel on peritoneal dissemination of gastric cancer. Cancer Lett 2004;210:189–196.CrossRefPubMedGoogle Scholar
  33. 33.
    Markman M, Rowinsky E, Harkes T, Reichman B, Jones W, Lewis JL Jr, et al. Phase I trial of intraperitoneal Taxol: a Gynecologic Oncology Group Study. J Clin Oncol 1992;10:1485–1491.PubMedGoogle Scholar
  34. 34.
    Tamura S, Miki H, Okada K, Miyake T, Yoshimura M, Suzuki R, et al. Pilot study of intraperitoneal administration of paclitaxel and oral S-1 for patients with peritoneal metastasis due to advanced gastric cancer. Int J Clin Oncol 2008;13:536–540.CrossRefPubMedGoogle Scholar
  35. 35.
    Yamada Y, Shirao K, Ohtsu A, Boku N, Hyodo I, Saitoh H, et al. Phase II trial of paclitaxel by 3-hour infusion for advanced gastric cancer with short premedication for prophylaxis against paclitaxel-associated hypersensitivity reaction. Ann Oncol 2001;12:1133–1137.CrossRefPubMedGoogle Scholar
  36. 36.
    Yamaguchi K, Tada M, Horikoshi N, Otani T, Takiuchi H, Saitoh S, et al. Paclitaxel Gastric Cancer Study Group in Japan, phase II study of paclitaxel with 3-h infusion in patients with advanced gastric cancer. Gastric Cancer 2002;5:90–95.CrossRefPubMedGoogle Scholar
  37. 37.
    Kodera Y, Ito S, Mochizuki Y, Fujikake S, Koshikawa K, Kanyama Y, et al. Chubu Clinical Cancer Group. A phase II study of weekly paclitaxel as second-line chemotherapy for advanced gastric cancer (CCOG0302 study). Anticancer Res 2007;27:2667–2671.PubMedGoogle Scholar
  38. 38.
    Emi Y, Yamamoto M, Takahashi I, Orita H, Kakeji Y, Kohnoe S, et al. Phase II study of weekly paclitaxel by 1-hour infusion for advanced gastric cancer. Surg Today 2008;38:1013–1020.CrossRefPubMedGoogle Scholar
  39. 39.
    Ueda Y, Yamagishi H, Ichikawa D, Mori J, Koizumi K, Kakihara N, et al. Phase I study of a combination of S-1 and weekly paclitaxel in patients with advanced or recurrent gastric cancer. Oncology 2005;69:261–268.CrossRefPubMedGoogle Scholar
  40. 40.
    Li C, Yan M, Chen J, Xiang M, Zhu ZG, Yin HR, et al. Survival benefit of non-curative gastrectomy for gastric cancer patients with synchronous distant metastasis. J Gastrointest Surg 2010;14:282–288.CrossRefPubMedGoogle Scholar
  41. 41.
    Kodera Y, Ito S, Mochizuki Y, Kondo K. Koshikawa K, Suzuki N, et al. A phase II study of radical surgery followed by postoperative chemotherapy with S-1 for gastric carcinoma with free cancer cells in the peritoneal cavity (CCOG0301 study). Eur J Sur Oncol 2009;35:1158–1163.Google Scholar

Copyright information

© The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2010

Authors and Affiliations

  • Shigeyuki Tamura
    • 1
  • Hirofumi Miki
    • 1
  • Kaoru Okada
    • 1
  • Atsushi Takeno
    • 1
  • Kumiko Uji
    • 1
  • Atsuko Yoshida
    • 1
  • Rei Suzuki
    • 1
  • Shin Nakahira
    • 1
  • Chiyomi Egawa
    • 1
  • Ken Nakata
    • 1
  • Shu Okamura
    • 1
  • Keishi Sugimoto
    • 1
  • Yuichi Takatsuka
    • 1
  1. 1.Department of SurgeryKansai Rosai HospitalHyogoJapan

Personalised recommendations