Survival Efficacy of Adjuvant Cytosine-Analogue CS-682 in a Fluorescent Orthotopic Model of Human Pancreatic Cancer
| Autor: | Robert M. Hoffman, Daniel Spivack, Shinako Takimoto, Matthew H.G. Katz, Abdool R. Moossa, Michael Bouvet |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty medicine.medical_treatment Mice Nude Gastroenterology Cytosine Mice Pancreatic tumor Oral administration Cell Line Tumor Internal medicine Pancreatic cancer medicine Animals Humans Disseminated disease Chemotherapy business.industry medicine.disease Surgery Pancreatic Neoplasms medicine.anatomical_structure Oncology Chemotherapy Adjuvant Toxicity Arabinonucleosides Pancreas business Adjuvant |
| Zdroj: | Cancer Research. 64:1828-1833 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-03-3350 |
| Popis: | Adjuvant treatment with the cytosine analogue 1-(2-C-cyano-2-deoxy-β-d-arabino-pentofuranosyl)-N4-palmitoylcytosine (CS-682) results in a highly significant increase in survival in the aggressive orthotopic MIA-PaCa-2 human pancreatic cancer mouse model. Seven days after implantation, mice were randomized into eight groups, depending on whether they were to be treated by tumor resection, 5 weeks of CS-682 chemotherapy at 40–60 mg/kg once daily, or both. Throughout the course of treatment, noninvasive optical whole-body imaging based on brilliant red fluorescent protein expression of the tumor permitted visualization and quantification of primary, metastatic, and recurrent disease. Total tumor burden negatively correlated with survival. Untreated mice died of disseminated disease with a median survival of 26 days. Surgical resection alone conferred a small but significant survival advantage (median survival, 28 days, P = 0.03). Primary CS-682 treatment at all doses also significantly prolonged survival compared with untreated animals (P < 0.05) and was more effective than surgery alone at doses of 50 and 60 mg/kg (median survival, 34 days, P = 0.045, and 38.5 days, P = 0.03, respectively). Maximal survival (median, 48 days, with 30% of animals surviving longer than 60 days) was achieved by adjuvant CS-682 (50 mg/kg), given after surgical resection of the primary pancreatic tumor (P = 0.004 compared with surgery alone). The results demonstrate that adjuvant oral administration of CS-682 for pancreatic cancer is highly effective with acceptable toxicity, suggesting its potential for cure of this disease in appropriate combinations. |
| Databáze: | OpenAIRE |
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