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Investigational New Drugs

, Volume 34, Issue 5, pp 636–642 | Cite as

Intravenous and intraperitoneal paclitaxel with S-1 for treatment of refractory pancreatic cancer with malignant ascites

  • Naminatsu Takahara
  • Hiroyuki IsayamaEmail author
  • Yousuke Nakai
  • Hironori Ishigami
  • Sohei Satoi
  • Suguru Mizuno
  • Hirofumi Kogure
  • Saburo Matsubara
  • Natsuyo Yamamoto
  • Hironori Yamaguchi
  • Minoru Tada
  • Joji Kitayama
  • Toshiaki Watanabe
  • Kazuhiko Koike
PHASE II STUDIES

Summary

Objectives The aim of this study was to evaluate the safety and efficacy of intravenous and intraperitoneal paclitaxel (PTX) combined with S-1 for treatment of gemcitabine-refractory pancreatic cancer with malignant ascites. Methods After the feasibility of this regimen was first confirmed in an interim analysis in 10 patients, a total of 35 patients were enrolled between April 2011 and December 2014. PTX was administered intravenously (50 mg/m2) and intraperitoneally (20 mg/m2) on days 1 and 8, and 80 mg/m2 S-1 was administered on days 1–14 every 3 weeks. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), the objective tumor response, efficacy against malignant ascites, and safety. Result In all 35 patients, the median OS and PFS were 4.8 (95 % confidence interval [CI], 2.1–5.3) months and 2.8 (95 % CI, 0.9–4.1) months, respectively. The 26 patients who were evaluable for efficacy achieved a response rate of 8 % and a disease control rate of 69 %. Malignant ascites had disappeared or decreased in 18 (69 %) patients, including complete resolution in 4 (15 %), and a negative change in cytological status was achieved in 8 (31 %) patients. The major grade 3/4 adverse events included neutropenia (34 %), anemia (31 %), nausea (9 %), and catheter-related infections (6 %). Conclusion Combination chemotherapy consisting of intravenous and intraperitoneal PTX with S-1 showed acceptable toxicity and favorable efficacy in pancreatic cancer patients with malignant ascites. (Clinical trial registration number: UMIN000005306)

Keywords

Pancreatic cancer Malignant ascites Peritoneal metastasis S-1 Paclitaxel Intraperitoneal chemotherapy 

Abbreviations

PTX

paclitaxel

i.v.

intravenous

i.p.

intraperitoneal

OS

overall survival

PFS

progression-free survival

RECIST

Response Evaluation Criteria in Solid Tumors

RR

response rate

PS

performance status

CEA

carcinoembryonic antigen

Notes

Acknowledgments

We thank all the participating patients and their families, as well as additional investigators, and the research coordinators Miyuki Tsuchida and Chiho Takeda (Department of Gastroenterology, The University of Tokyo Hospital).

Compliance with ethical standards

Conflicts of interest and source of funding

Drs Hiroyuki Isayama, Hironori Ishigami Toshiaki Watanabe, and Kazuhiko Koike are currently receiving a grant from TAIHO Pharmaceutical Co., Ltd. For the remaining authors have no relevant disclosures. This work was supported in part by the Tokyo University Research Fund.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Naminatsu Takahara
    • 1
  • Hiroyuki Isayama
    • 1
    Email author
  • Yousuke Nakai
    • 1
  • Hironori Ishigami
    • 2
  • Sohei Satoi
    • 3
  • Suguru Mizuno
    • 1
  • Hirofumi Kogure
    • 1
  • Saburo Matsubara
    • 1
  • Natsuyo Yamamoto
    • 1
  • Hironori Yamaguchi
    • 4
  • Minoru Tada
    • 1
  • Joji Kitayama
    • 4
  • Toshiaki Watanabe
    • 5
  • Kazuhiko Koike
    • 1
  1. 1.Department of Gastroenterology, Graduate School of MedicineThe University of TokyoTokyoJapan
  2. 2.Department of ChemotherapyThe University of TokyoTokyoJapan
  3. 3.Department of SurgeryKansai Medical UniversityOsakaJapan
  4. 4.Department of SurgeryJichi Medical University School of MedicineTochigiJapan
  5. 5.Department of Surgical OncologyThe University of TokyoTokyoJapan

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