A Phase II study of gemcitabine plus zoledronic acid in subjects with Stage IV pancreatic cancer

Autor: Michael A. Monticelli, J. V. Cox, Kristi A. Boehm, Marcus A. Neubauer, John Sandbach, Thomas H. Cartwright, Des Ilegbodu, Lina Asmar, D. McCollum
Rok vydání: 2006
Předmět:
Zdroj: Journal of Clinical Oncology. 24:14002-14002
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2006.24.18_suppl.14002
Popis: 14002 Background: Gemcitabine, the standard chemotherapy for advanced pancreatic cancer (APC), produces low response rates and short time to progression. Preclinical studies suggest that zoledronic acid inhibits pancreatic cell lines by interfering with the p21ras/raf-1/MEK1/ERKL signaling pathway. We conducted this trial to evaluate the efficacy and toxicity of gemcitabine and zoledronic acid in subjects with APC. Methods: Eligible subjects had histological or cytological diagnosis of metastatic pancreatic adenocarcinoma (Stage IV) not amenable to resection with curative intent. Gemcitabine 1000 mg/m2 IV was given on Days 1, 8, 15, and 22 in Cycle 1 and Days 1, 8, and 15 in subsequent cycles. Zoledronic acid 4 mg IV was given on Day 1 every 4 weeks. Toxicity was assessed at each visit. Results: Between December 2004 and July 2005, 35 subjects were enrolled. Baseline characteristics: 20 males (57%), median age 66.7 years (range, 40–83.5), and KPS of 70/80/90/100 = 8%/29%/34%/29%, respectively. Four patients had locally advanced disease (3 stage IIB and 1 stage III), 86% of subjects had Stage IV disease at diagnosis; 91% of subjects had adenocarcinoma. Prior therapy included surgery (n=15, 43%), chemotherapy (n=3, 9%), and radiotherapy (n=2, 6%). To date, there has been 1 PR and 9 SD; the clinical benefit rate (PR+SD≥6 months) was 14%. Grade 3 and 4 treatment-related toxicities included: neutropenia (22%); thrombocytopenia and fatigue, (12.5% each); and anemia, nausea/vomiting, dehydration, and diarrhea (6% each). Seven treatment-related SAEs have been reported; 28 subjects are off study. Patients discontinued treatment due to: progressive disease (PD) (n=15), toxicity (n=4, 1 each DVT, infection, back pain, and generalized weakness), withdrew consent (n=3), MD decision (n=2), patient request (n=2), and death (n=2), To date, 21 subjects have died; deaths were attributed to PD (n=16), CVA (n=1), and unknown (n=4). Conclusions: Pancreatic cancer, typically advanced at diagnosis, remains a major treatment challenge. Zoledronic acid in combination with gemcitabine was well-tolerated in this study. Future genomic testing is proposed for responders. Updated toxicity, response, and survival data will be presented. Supported by Novartis Pharmaceuticals Corp., East Hanover, NJ. No significant financial relationships to disclose.
Databáze: OpenAIRE
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