Adjuvant therapy for pancreas cancer in an era of value based cancer care

Ahn, Daniel H.; Williams, Terence M.; Goldstein, Daniel A.; El‐Rayes, Bassel F.; Bekaii‐Saab, Tanios

doi:10.1016/j.ctrv.2015.11.004

Cited by 16 publications

(13 citation statements)

References 69 publications

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“…If our study had included the cost associated with radiation and chemotherapy and indirect costs, the mean cost incurred by the patients would be much higher. Approximately 50% to 60% of patients receive adjuvant chemotherapy with gemcitabine and, given the negative results from adjuvant chemoradiation, only selected patients with margin-positive disease received adjuvant chemoradiation.. 31 , 32 …”

Section: Discussionmentioning

confidence: 99%

Financial Impact of Complex Cancer Surgery in India: A Study of Pancreatic Cancer

Basavaiah

Rent

et al. 2018

JGO

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PurposeThe rapidly increasing burden of cancer in India has profound impacts on health care costs for patients and their families. High out-of-pocket (OOP) expenditure, lack of insurance, and low government expenditure create a vicious cycle, leading to household impoverishment. Complex cancer surgery is now increasingly important for emerging countries; however, little is understood about the macro- and microeconomics of these procedures. After the Lancet Oncology Commission on Global Cancer Surgery, we evaluated the OOP expenditure for patients undergoing pancreatico-duodenectomy (PD) at a government tertiary cancer center in India.MethodsProspective data from 98 patients who underwent PD between January 2014 and June 2015 were collected and analyzed. The time frame for consideration of expenses, including all preoperative investigations, was from the first hospital visit to the day of discharge. Catastrophic expenditure was calculated by assessing the percentage of households in which OOP health payments exceeded 10% of the total household income.ResultsThe mean expenditure for PD by patients was Rs.295,679.57 (US$74,420, purchasing power parity corrected). This amount was significantly higher among those admitted to a private ward and those with complications. Only 29.6% of the patients had insurance coverage. A total of 76.5% of the sample incurred catastrophic expenditure, and 38% of those with insurance underwent financial catastrophe compared with 93% of those without insurance. The percentage of patients facing catastrophic impact was highest among those in semiprivate wards, at 86.7%, followed by those in public and private wards.ConclusionThe cost of PD is high and is often unaffordable for a majority of India’s population. A review of insurance coverage policies for better coverage must be considered.

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Section: Discussionmentioning

confidence: 99%

Financial Impact of Complex Cancer Surgery in India: A Study of Pancreatic Cancer

Basavaiah

Rent

et al. 2018

JGO

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“…However, treatment with GEM leads to only a modest improvement in overall survival of PDAC patients [ 3 ]. To increase GEM's efficacy, adjuvant therapies such as 5-fluorouracil, nab-paclitaxel, or cisplatin are often used [ 4 ]. These agents target other mechanisms used by cancer cells to grow and divide.…”

Section: Introductionmentioning

confidence: 99%

Piperlongumine potentiates the effects of gemcitabine in in vitro and in vivo human pancreatic cancer models

et al. 2017

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Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers due to a late diagnosis and poor response to available treatments. There is a need to identify complementary treatment strategies that will enhance the efficacy and reduce the toxicity of currently used therapeutic approaches. We investigated the ability of a known ROS inducer, piperlongumine (PL), to complement the modest anti-cancer effects of the approved chemotherapeutic agent gemcitabine (GEM) in PDAC cells in vitro and in vivo. PDAC cells treated with PL + GEM showed reduced cell viability, clonogenic survival, and growth on Matrigel compared to control and individually-treated cells. Nude mice bearing orthotopically implanted MIA PaCa-2 cells treated with both PL (5 mg/kg) and GEM (25 mg/kg) had significantly lower tumor weight and volume compared to control and single agent-treated mice. RNA sequencing (RNA-Seq) revealed that PL + GEM resulted in significant changes in p53-responsive genes that play a role in cell death, cell cycle, oxidative stress, and DNA repair pathways. Cell culture assays confirmed PL + GEM results in elevated ROS levels, arrests the cell cycle in the G0/G1 phase, and induces PDAC cell death. We propose a mechanism for the complementary anti-tumor effects of PL and GEM in PDAC cells through elevation of ROS and transcription of cell cycle arrest and cell death-associated genes. Collectively, our results suggest that PL has potential to be combined with GEM to more effectively treat PDAC.

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“…Pancreatic cancer is one of the most aggressive and lethal malignancy. While significant improvements have been made in the management of other cancers, the mortality of pancreatic ductal adenocarcinoma (PDAC) remains high, with a 5-year survival rate of 7% [1,2], and ranks as the seventh leading cause of cancer deaths globally [3]. The chemotherapy regimen for PDAC is not effective in many cases due to the poor response or development of drug resistance [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…Generally, several potential mechanisms dictate drug sensitivity or the development of resistance to chemotherapy: (1) The intracellular concentrations of small, hydrophobic, nonpolar drug molecules can be reduced by cell membrane pumps through efflux mechanisms. It is well recognized that the overexpression of the P-glycoprotein (MDR1) leads to increased drug resistance [12,13].…”

Section: Introductionmentioning

confidence: 99%

HE4 overexpression decreases pancreatic cancer Capan-1 cell sensitivity to paclitaxel via cell cycle regulation

Guo

et al. 2020

Cancer Cell Int

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Background: Paclitaxel is a first-line chemotherapy drug for pancreatic, ovarian, endometrial cancers and other malignancies. However, its efficacy is often compromised by decreased cell sensitivity or the development of resistance. Human epididymis protein 4 (HE4) is highly expressed in gynecologic and pancreatic cancer tissues, and its serum levels are used for patient triage and assistant diagnosis of gynecologic cancers. Previous studies have shown that HE4 overexpression could promote cancer cell proliferation and the growth of tumor xenografts, which suggests its potential involvement in cancer chemosensitivity. Methods: Two pancreatic cancer cell lines, Capan-1 and Suit-2, were transiently transfected with an HE4 overexpression plasmid, and transfected cells were treated with paclitaxel. S-phase cells were labeled using BrdU, and cell positivity rates were determined by counting BrdU-positive cells. Following HE4 overexpression and/or drug treatment, a western blotting analysis was performed to determine the protein alterations of PCNA and p21, two important cell cycle regulators. Results: HE4 overexpression not only promoted the proliferation of the Capan-1 pancreatic cells, but also significantly decreased cell sensitivity to paclitaxel. Results from western blotting showed that paclitaxel inhibited cell proliferation by decreasing the expression of PCNA and increasing the expression of p21. Data analysis indicated interactive actions between HE4 function and paclitaxel effects, both converging to cell cycle regulation. Conclusion: These findings suggest that HE4 could be a potential therapeutic target for the sensitization of pancreatic cancer cells to paclitaxel treatment. HE4 expression levels may be used to predict the sensitivity of pancreatic cancer patients to paclitaxel.

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Adjuvant therapy for pancreas cancer in an era of value based cancer care

Cited by 16 publications

References 69 publications

Financial Impact of Complex Cancer Surgery in India: A Study of Pancreatic Cancer

Financial Impact of Complex Cancer Surgery in India: A Study of Pancreatic Cancer

Piperlongumine potentiates the effects of gemcitabine in in vitro and in vivo human pancreatic cancer models

HE4 overexpression decreases pancreatic cancer Capan-1 cell sensitivity to paclitaxel via cell cycle regulation

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