A phase II study of sorafenib, oxaliplatin, and 2 days of high-dose capecitabine in advanced pancreas cancer.

Abstract

PURPOSE:

Fluoropyrimidines and oxaliplatin have demonstrated some efficacy against pancreatic adenocarcinoma, but survival remains brief. Sorafenib is an oral multikinase inhibitor which we sought to combine with a unique capecitabine and oxaliplatin regimen for pancreatic adenocarcinoma.

METHODS:

We performed a multicenter phase II study of sorafenib 200 mg orally twice daily along with oxaliplatin 85 mg/m(2) IV on days 1 and 15, followed by capecitabine 2250 mg/m(2) orally every 8 h for six doses starting on days 1 and 15 of a 28-day cycle in patients who had no more than one previous chemotherapy regimen for their pancreatic adenocarcinoma. The primary objective was response rate; secondary objectives were progression-free survival (PFS), overall survival (OS), and safety.

RESULTS:

Twenty-four patients were enrolled; median age was 63 years (range 48-83). The most common related toxicities were fatigue, neuropathy, anemia, thrombocytopenia, diarrhea, nausea, leukopenia, and hand-foot syndrome. Grade 3 hand-foot syndrome was rare (4 %). Other grade 4 toxicities included abdominal pain (8 %), pulmonary embolism (4 %), and anemia (4 %). Three partial responses were seen (13 %), and 11 patients had stable disease (46 %) as their best response. Median PFS was 6.0 months (range 1.5-13 months). Median OS was 8.1 months (range 1.5-13.6 months).

CONCLUSIONS:

Sorafenib, oxaliplatin, and capecitabine produced partial responses in patients with advanced pancreatic cancer including previously treated patients and demonstrated a PFS of 6 months with few grade 3/4 toxicities.

• Authors: Rory J Makielski, Sam J Lubner, Daniel L Mulkerin, Anne M Traynor, David Groteluschen, Jens Eickhoff, Noelle K LoConte
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 76 Issue 2 Pg. 317-23 (Aug 2015) ISSN: 1432-0843 [Electronic] Germany
• PMID: 26068189 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Organoplatinum Compounds
• Phenylurea Compounds
• Pyridines
• oxiplatin
• Deoxycytidine
• Niacinamide
• Capecitabine
• Sorafenib
• Fluorouracil

Topics

• Adenocarcinoma (drug therapy)
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Capecitabine
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Female
• Fluorouracil (administration & dosage, analogs & derivatives)
• Humans
• Male
• Middle Aged
• Niacinamide (administration & dosage, analogs & derivatives)
• Organoplatinum Compounds (administration & dosage)
• Pancreatic Neoplasms (drug therapy)
• Phenylurea Compounds (administration & dosage)
• Pyridines (administration & dosage)
• Sorafenib