Attenuated FOLFIRINOX in the salvage treatment of gemcitabine-refractory advanced pancreatic cancer: a phase II study

Jung Hoon Kim, Sang Cheol Lee, Sung Yong Oh, Seo Young Song, Namsu Lee, Eun Mi Nam, Soonil Lee, In Gyu Hwang, Hyo Rak Lee, Kyu Taek Lee, Sang Byung Bae, Han Jo Kim, Joung Soon Jang, Do Hyoung Lim, Hyun Woo Lee, Seok Yun Kang, Jung Hun Kang

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19 Scopus citations

Abstract

Background: Combination therapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) chemotherapy drastically improves survival of advanced pancreatic cancer patients. However, the efficacy of FOLFIRINOX as a second-line treatment after gemcitabine failure has not been tested prospectively. We investigated the feasibility and safety of attenuated FOLFIRINOX in patients with gemcitabine-refractory advanced pancreatic cancer. Methods: A multicenter phase II prospective open-label, single-arm study was conducted at 14 hospitals. Patients with histologically proven invasive ductal pancreatic adenocarcinoma, a measurable or evaluable lesion, Eastern Cooperative Oncology Group performance status 0 or 1, adequate organ function, and aged 19 years or older were eligible. Attenuated FOLFIRINOX consisted of oxaliplatin 65 mg/m2, irinotecan 135 mg/m2, and leucovorin 400 mg/m2 injected intravenously on day 1 and 5-fluorouracil 2000 mg/m2 continuously infused intravenously over 46 h on days 1–2, repeated every 2 weeks. The primary endpoint was progression-free survival from the initiation of FOLFIRINOX. Secondary endpoints were the objective response rate, disease control rate, overall survival, safety, and tolerability. We estimated overall survival and progression-free survival using the Kaplan–Meier methods. Results: We enrolled 39 patients from 14 institutions. The objective response rate was 10.3%, while the disease control rate was 64.1%. The 6-month and 1-year overall survival rates were 59.0% and 15.4%, respectively. Median progression-free survival and overall survival were 3.8 months (95% confidence interval [CI] 1.5–6.0 months) and 8.5 months (95% CI 5.6–11.4 months), respectively. Grade 3 or 4 adverse events were neutropenia (41.0%), nausea (10.3%), anorexia (10.3%), anemia (7.7%), mucositis (7.7%), pneumonia/pleural effusion (5.1%), and fatigue (5.1%). One treatment-related death attributable to septic shock occurred. Conclusion: Attenuated FOLFIRINOX may be promising as a second-line therapy for gemcitabine-refractory pancreatic cancer.

Original languageEnglish
Article number32
JournalCancer communications (London, England)
Volume38
Issue number1
DOIs
StatePublished - Dec 2018

Bibliographical note

Funding Information:
The present study was supported by a research Grant from Hanmi Pharma‑ ceutical Co. Ltd., and the Soonchunhyang University Research fund.

Funding Information:
The present study was supported by a research Grant from Hanmi Pharmaceutical Co. Ltd., and the Soonchunhyang University Research fund.

Publisher Copyright:
© The Author(s) 2018.

Keywords

  • Attenuated FOLFIRINOX
  • Gemcitabine
  • Pancreatic cancer
  • Second-line

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