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

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.

• Authors: 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
• Journal: Cancer communications (London, England) (Cancer Commun (Lond)) Vol. 38 Issue 1 Pg. 32 (06 04 2018) ISSN: 2523-3548 [Electronic] United States
• PMID: 29866170 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Drug Combinations
• Organometallic Compounds
• folfirinox
• Oxaliplatin
• Deoxycytidine
• Irinotecan
• Leucovorin
• Fluorouracil
• Gemcitabine

Topics

• Adenocarcinoma (drug therapy)
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Deoxycytidine (analogs & derivatives, therapeutic use)
• Drug Combinations
• Drug Resistance, Neoplasm
• Female
• Fluorouracil (administration & dosage, adverse effects)
• Humans
• Irinotecan (administration & dosage, adverse effects)
• Kaplan-Meier Estimate
• Leucovorin (administration & dosage, adverse effects)
• Male
• Middle Aged
• Nausea (chemically induced)
• Neutropenia (chemically induced)
• Organometallic Compounds (administration & dosage, adverse effects)
• Oxaliplatin (administration & dosage, adverse effects)
• Pancreatic Neoplasms (drug therapy)
• Prospective Studies
• Salvage Therapy (adverse effects, methods)
• Gemcitabine