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U.S. Department of Health and Human Services

Drugs

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Paclitaxel

On September 6, 2013, the U. S. Food and Drug Administration approved paclitaxel protein-bound particles (albumin-bound) (Abraxane for injectable suspension, Abraxis BioScience, LLC, a wholly owned subsidiary of Celgene Corporation), in combination with gemcitabine for the first-line treatment of patients with metastatic adenocarcinoma of the pancreas.

 
The approval of Abraxane for this indication was based on the demonstration of improved overall survival (OS) in a multi-center, international, open-label, randomized trial enrolling 861 patients with metastatic pancreatic cancer. Patients were randomized to receive either the combination of Abraxane plus gemcitabine (n=431) or gemcitabine alone (n=430).  Randomization was stratified by geographic region (Australia, Western Europe, Eastern Europe, or North America), performance status, and presence of liver metastasis. The major efficacy outcome measure was OS and additional outcome measures were progression-free survival (PFS) and overall response rate (ORR), both assessed by independent, central, blinded radiological review using RECIST (version 1.0).
 
The median age of the patients was 63 years (range 27-88 years) with 42% age 65 years or older, 58% were men, and the Karnofsky performance was 90 or 100 in 60%. Nearly half (46%) of the patients had three or more sites of metastatic disease and 84% had liver metastases. The primary lesion was located in the pancreatic head in 43%, the body in 31%, or tail in 25% of patients.
 
The trial demonstrated a statistically significant prolongation of OS for patients randomized to receive the combination of Abraxane plus gemcitabine [HR 0.72 (95% CI: 0.62, 0.84); p < 0.0001, stratified log-rank test]. The median OS was 8.5 months in the Abraxane plus gemcitabine arm and 6.7 months in the single agent gemcitabine arm. A significant improvement in PFS was also observed with median PFS of 5.5 months in the Abraxane plus gemcitabine arm and 3.7 months in the gemcitabine arm [HR 0 .69 (95% CI: 0.58, 0.82) p < 0.0001, stratified log-rank test]. Objective response rates were 23% and 7% in the Abraxane plus gemcitabine and single agent gemcitabine arms, respectively (p<0.0001, Chi-square test). 
 
The most frequent (≥20% incidence) adverse reactions reported at a ≥5% higher incidence in patients who received the combination of Abraxane plus gemcitabine as compared to gemcitabine alone included neutropenia, fatigue, peripheral neuropathy, nausea, alopecia, peripheral edema, diarrhea, pyrexia, vomiting, decreased appetite, rash, and dehydration.
 
The most frequent serious adverse reactions in patients who received the combination were pyrexia, dehydration, pneumonia, and vomiting. Sepsis was reported in 5% and pneumonitis was reported in 4% of patients who received Abraxane plus gemcitabine. 
 
The recommended dose and schedule for Abraxane is 125 mg/m2 administered as an intravenous infusion over 30-40 minutes on days 1, 8 and 15 of each 28-day cycle until disease progression or if no longer tolerated by the patient. Gemcitabine is administered immediately after Abraxane on days 1, 8 and 15 of each 28-day cycle.
 
Full prescribing information is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021660s037lbl.pdf
 
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).