levoleucovorin and olaparib

Personalized medicine in treating pancreatic ductal adenocarcinoma (PDAC) is still in its infancy, albeit PDAC-related deaths are projected to rise over the next decade. Only recently, maintenance therapy with the PARP inhibitor olaparib showed improved progression-free survival in germline

Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Ataxia Telangiectasia Mutated Proteins; BRCA2 Protein; Carcinoma, Pancreatic Ductal; Cell Line, Tumor; Chromosomal Instability; DNA Damage; Female; Fluorouracil; Gene Expression Regulation, Neoplastic; Humans; Irinotecan; Leucovorin; Maintenance Chemotherapy; Mice; Mice, Nude; Middle Aged; Oxaliplatin; Pancreatic Neoplasms; Phthalazines; Piperazines; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Survival Analysis; Ubiquitin-Protein Ligases; Xenograft Model Antitumor Assays

Pancreatic acinar cell carcinoma (PACC) is a relatively rare malignancy of the exocrine pancreas. BRCA2, a cancer susceptibility gene, has been widely studied in breast and ovarian carcinomas as mutation carriers for this gene are at a high risk for cancer development. Olaparib, an oral poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor, has been approved for the treatment of ovarian cancer with any BRCA 1/2 mutations. Herein, we report the first case of a germline BRCA2-mutated unresectable advanced PACC patient who responded well to olaparib treatment.. A 59-year-old male with a family history of cancer presented with a persistent epigastric dull pain for 3 months.. The patient was diagnosed with advanced PACC based on computed tomography (CT) scan, laparotomy, and pathology.. Exploratory laparotomy, intratumoral brachytherapy by radioiodine-125 seeds, modified FOLFIRINOX chemotherapy, and targeted therapy with olaparib were administered.. The patient responded well to olaparib until the occurrence of severe adverse drug reactions, he died as a result of multiple organ failure with an overall survival period of 12 months.. As a PARP inhibitor, olaparib has remarkable curative effect not only on breast and ovarian cancers, but also on other malignancies with BRCA mutations. Patients with advanced cancer could benefit from active targeted therapy with improvement in overall survival and quality of life.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; BRCA2 Protein; Carcinoma, Acinar Cell; Drug Combinations; Fatal Outcome; Fluorouracil; Humans; Irinotecan; Laparotomy; Leucovorin; Male; Middle Aged; Mutation; Organometallic Compounds; Oxaliplatin; Pancreatic Neoplasms; Phthalazines; Piperazines; Tomography, X-Ray Computed