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Medication

Medication Summary

The most active agents for pancreatic cancer have been 5-fluorouracil (5-FU) and gemcitabine. Gemcitabine appears to be slightly more active than 5-FU. Both of those agents are commonly used in combination regimens—for example, 5-FU plus folinic acid [leucovorin], irinotecan, and oxaliplatin (FOLFIRINOX); and gemcitabine plus capecitabine (GemCap). Objective responses, meaning actual regression of tumor, have been 20% or less.

Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is used for maintenance therapy in pancreatic adenocarcinoma. Olaparib has US Food and Drug Administration (FDA) approval for adults with germline BRCA-mutated metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen.^[8]

Class Summary

These agents inhibit cell growth and proliferation. They are used for chemotherapy.

Gemcitabine (Gemzar)

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A frequently quoted trial showed a small, but statistically significant, improvement in overall survival with gemcitabine versus 5-FU (5.7 vs 4.4 mo). Additionally, gemcitabine improved the quality of life in approximately 25% of patients. It is a pyrimidine antimetabolite that nhibits DNA polymerase and ribonucleotide reductase, which in turn inhibit DNA synthesis.

Fluorouracil (Adrucil)

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This is a fluorinated pyrimidine antimetabolite that inhibits thymidylate synthase (TS) and also interferes with ribonucleic acid (RNA) synthesis and function. Fluorouracil has some effect on DNA and is useful in symptom palliation for patients with progressive disease. It is commonly used in patients with gastrointestinal malignancies. Response rates are typically less than 20% in pancreatic cancer.

Erlotinib (Tarceva)

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This agent is pharmacologically classified as a human epidermal growth factor receptor type 1/epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor. EGFR is expressed on the cell surface of normal cells and cancer cells. Erlotinib has been approved by the FDA for use, in combination with gemcitabine, as a first-line treatment for locally advanced, unresectable, or metastatic pancreatic cancer.

Capecitabine (Xeloda)

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Capecitabine is a prodrug of fluorouracil that undergoes hydrolysis in liver and tissues to form the active moiety (fluorouracil), inhibiting thymidylate synthetase, which in turn blocks methylation of deoxyuridylic acid to thymidylic acid. This step interferes with DNA, and to a lesser degree with RNA synthesis.

Paclitaxel protein bound (Abraxane)

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Paclitaxel protein bound is a microtubular inhibitor (albumin-conjugated formulation) and a natural taxane that prevents depolymerization of cellular microtubules, which results in DNA, RNA, and protein synthesis inhibition. It is indicated for metastatic adenocarcinoma of the pancreas as first-line treatment in combination with gemcitabine.

Irinotecan liposomal (Onivyde)

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Irinotecan sucrosofate salt in a pegylated liposomal formulation. Irinotecan and its active metabolite SN-38 bind reversibly to the topoisomerase-1 DNA complex and prevent re-ligation of the single-strand breaks, leading to exposure time-dependent double-strand DNA damage and cell death. Irinotecan liposomal is used in combination with fluorouracil and leucovorin for metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy.

Olaparib (Lynparza)

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Olaparib is a poly (DP-ribose) polymerase (PARP) inhibitor. PARP enzymes are involved in normal cellular function (eg, DNA transcription and repair). It is indicated for maintenance treatment of adults with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen.

Oxaliplatin (Eloxatin)

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Platinum coordination compound that inhibits DNA synthesis; cross-links and denatures strands of DNA; disrupts DNA function by covalently binding to DNA bases.

Questions

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Media Gallery

Pancreatic cancer. Gross section of an adenocarcinoma of the pancreas measuring 5 × 6 cm resected from the pancreatic body and tail. Although the tumor was considered to have been fully resected and had not spread to any nodes, the patient died of recurrent cancer within 1 year.
Pancreatic cancer. Hematoxylin and eosin stain of a pancreatic carcinoma. Note the intense desmoplastic response around the neoplastic cells. The large amount of fibrotic reaction in these tumors can make obtaining adequate tissue by fine-needle aspiration difficult.
Pancreatic cancer. T staging for pancreatic carcinoma. T1 and T2 stages are confined to the pancreatic parenchyma. T3 lesions invade local structures such as the duodenum, bile duct, and/or major peripancreatic veins, and T4 lesions invade surrounding organs (eg, stomach, colon, liver) or invade major arteries such as the superior mesenteric or celiac arteries.
Pancreatic cancer. Computerized tomographic scan showing a pancreatic adenocarcinoma of the pancreatic head. The gallbladder (gb) is distended because of biliary obstruction. The superior mesenteric artery (sma) is surrounded by tumor, making this an unresectable T4 lesion.
Pancreatic cancer. Abdominal CT scan of a small, vaguely seen, 2-cm pancreatic adenocarcinoma (mass) causing obstruction of both the common bile duct (cbd) and pancreatic duct (pd).
Pancreatic cancer. Endoscopic ultrasound of a 2.2-cm pancreatic adenocarcinoma of the head of the pancreas obstructing the common bile duct (CBD) but not invading the portal vein (PV) or superior mesenteric vein (SMV). Findings from endoscopic ultrasound–guided fine-needle aspiration revealed a moderately to poorly differentiated adenocarcinoma. Abdominal CT findings did not show this mass, and an attempt at endoscopic retrograde cholangiopancreatography at another institution was unsuccessful.
Algorithm for evaluation of a patient with suspected pancreatic cancer. CT scanning for definitive diagnosis and staging must be with thin-cut, multidetector, spiral CT scanning using dual-phase contrast imaging to allow for maximal information. This schema varies among institutions depending on local expertise, research interest, and therapeutic protocols for pancreatic carcinoma.
Pancreatic cancer. Tip of linear array echoendoscope (Pentax FG 36UX) with 22-gauge aspiration needle exiting from biopsy channel. Insert shows magnification of aspiration needle tip. Note that the needle exits from the biopsy channel such that it appears continuously in the view of the ultrasonic transducer on the tip of the echoendoscope.
Pancreatic cancer. Cytologic samples from fine-needle aspirations (rapid Papanicolaou stain) of pancreatic adenocarcinomas. (A) Well differentiated, (B) moderately differentiated, (C) moderate to poorly differentiated, (D) poorly differentiated tumor.

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Pancreatic Cancer Medication

Medication Summary

Antineoplastic agents

Class Summary

Gemcitabine (Gemzar)

Gemcitabine (Gemzar)

Fluorouracil (Adrucil)

Fluorouracil (Adrucil)

Erlotinib (Tarceva)

Erlotinib (Tarceva)

Capecitabine (Xeloda)

Capecitabine (Xeloda)

Paclitaxel protein bound (Abraxane)

Paclitaxel protein bound (Abraxane)

Irinotecan liposomal (Onivyde)

Irinotecan liposomal (Onivyde)

Olaparib (Lynparza)

Olaparib (Lynparza)

Oxaliplatin (Eloxatin)

Oxaliplatin (Eloxatin)

Pancreatic Cancer Medication

Medication Summary

Antineoplastic agents

Class Summary

Gemcitabine (Gemzar)

Fluorouracil (Adrucil)

Erlotinib (Tarceva)

Capecitabine (Xeloda)

Paclitaxel protein bound (Abraxane)

Irinotecan liposomal (Onivyde)

Olaparib (Lynparza)

Oxaliplatin (Eloxatin)

References

Tables

Contributor Information and Disclosures

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