Induction chemotherapy with gemcitabine, oxaliplatin, and 5-fluorouracil/leucovorin followed by concomitant chemoradiotherapy in patients with locally advanced pancreatic cancer: a Taiwan cooperative oncology group phase II study.

Abstract

PURPOSE:

To evaluate the therapeutic efficacy of 3-month triplet induction chemotherapy (ICT) followed by concomitant chemoradiotherapy (CCRT) in patients with locally advanced pancreatic cancer (LAPC).

PATIENTS AND METHODS:

Chemonaïve patients with measurable, histologically confirmed LAPC were eligible. The ICT consisted of biweekly gemcitabine (800 mg/m2) infusion at a fixed dose rate (10 mg/m2/min), followed by 85 mg/m2 oxaliplatin and 48-h infusion of 5-fluorouracil/leucovorin (3000/150 mg/m2) for 6 cycles. Patients without disease progression 4 weeks after ICT would receive weekly 400 mg/m2 gemcitabine and 5040 cGy radiation in 28 fractions. After CCRT, patients were subjected for surgical intervention and/or maintenance chemotherapy until progression or intolerable toxicity.

RESULTS:

Between December 2004 and August 2008, 50 patients were enrolled. The best responses after ICT were partial response (PR) in 9, stable disease in 26, and progressive disease or not evaluable in 15. Among the former 35 patients, 2 had disease progression before CCRT, and 3 declined to have CCRT. Of the 30 patients receiving CCRT, an additional 4 and 1 patient(s) achieved PR at the end of CCRT and during maintenance chemotherapy, respectively. On intent-to-treat analysis, the overall best response was PR in 14 patients and stable disease in 21. The overall response rate and disease control rate were 28% (95% confidence interval [CI], 16.2-42.5%) and 70% (95% CI, 44.4-99.2%), respectively. The median time to progression and overall survival of the intent-to-treat population was 9.3 (95% CI, 5.8-12.8) months and 14.5 (95% CI, 11.9-17.1) months, respectively. One- and two-year survival rates were 68% (95% CI, 55.1-80.9%) and 20.6% (95% CI, 8.7-32.5%), respectively. Neutropenia was the most common Grade 3-4 toxicity of both ICT and CCRT, with a frequency of 28% and 26.7%, respectively. Significant sensory neuropathy occurred in 9 patients (18%).

CONCLUSION:

Three months of triplet ICT followed by gemcitabine-based CCRT is feasible, moderately active, and associated with encouraging survival in patients with LAPC.

• Authors: Hui-Ju Ch'ang, Yu-Lin Lin, Hsiu-Po Wang, Yen-Feng Chiu, Ming-Chu Chang, Chih-Hung Hsu, Yu-Wen Tien, Jen-Shi Chen, Ruey-Kuen Hsieh, Pin-Wen Lin, Yan-Shen Shan, Ann-Lii Cheng, Jang-Yang Chang, Jacqueline Whang-Peng, Tsann-Long Hwang, Li-Tzong Chen
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 81 Issue 5 Pg. e749-57 (Dec 01 2011) ISSN: 1879-355X [Electronic] United States
• PMID: 21420250 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Organoplatinum Compounds
• Oxaliplatin
• Deoxycytidine
• Leucovorin
• Fluorouracil
• Gemcitabine

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Chemoradiotherapy (adverse effects, methods)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Disease Progression
• Drug Administration Schedule
• Female
• Fluorouracil (administration & dosage)
• Humans
• Induction Chemotherapy (methods)
• Leucovorin (administration & dosage)
• Maintenance Chemotherapy
• Male
• Middle Aged
• Neutropenia (etiology)
• Organoplatinum Compounds (administration & dosage)
• Oxaliplatin
• Pancreatic Neoplasms (drug therapy, mortality, pathology, radiotherapy)
• Prospective Studies
• Radiotherapy Dosage
• Radiotherapy, Conformal (adverse effects)
• Survival Rate
• Taiwan
• Gemcitabine