Impact of nab-paclitaxel-based second-line chemotherapy on the outcomes of pancreatic cancer.

Dadi, Neelakanta; Shahda, Safi; O’Neil, Bert H.; Sehdev, Amikar

doi:10.1200/jco.2017.35.4_suppl.483

Cited by 8 publications

(13 citation statements)

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“…Patients were selected from the Indiana University Simon Cancer Center pancreatic cancer database, which is a large Institutional review board (IRB) approved high quality prospective and retrospective data collection repository (13). The main inclusion criterion (to allow for adequate available tissue) for the study was histologic diagnosis of recurrent pancreatic adenocarcinoma.…”

Section: Study Population and Patient Selectionmentioning

confidence: 99%

Germline and Somatic DNA Damage Repair Gene Mutations and Overall Survival in Metastatic Pancreatic Adenocarcinoma Patients Treated with FOLFIRINOX

Sehdev

Gbolahan

Hancock

et al. 2018

Clinical Cancer Research

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Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with lack of predictive biomarkers. We conducted a study to assess DNA damage repair (DDR) gene mutations as a predictive biomarker in PDAC patients treated with FOLFIRINOX. Indiana University Simon Cancer Center pancreatic cancer database was used to identify patients with metastatic PDAC, treated with FOLFIRINOX and had tissue available for DNA sequencing. Baseline demographic, clinical, and pathologic information was gathered. DNA isolation and targeted sequencing was performed using the Ion AmpliSeq protocol. Overall survival (OS) analysis was conducted using Kaplan-Meier, logistic regression and Cox proportional hazard methods. Multivariate models were adjusted for age, gender, margin status, CA 19-9, adjuvant chemotherapy, tumor and nodal stage. Overall, 36 patients were sequenced. DDR gene mutations were found in 12 patients. Mutations were seen in BRCA1 ( = 7), BRCA2 ( = 5), PALB2 ( = 3), MSH2 ( = 1), and FANCF ( = 1) of all the DDR genes sequenced. Median age was 65.5 years, 58% were male, 97.2% were Caucasian and 51.4% had any family history of cancer. The median OS was near significantly superior in those with DDR gene mutations present vs. absent [14 vs. 5 months; HR, 0.58; 95% confidence interval (CI), 0.29-1.14; log-rank = 0.08]. Multivariate logistic (OR, 1.47; 95% CI, 1.04-2.06; = 0.04) and Cox regression (HR, 0.37; 95% CI, 0.15-0.94; = 0.04) showed presence of DDR gene mutations was associated with improved OS. In a single institution, retrospective study, we found that the presence of DDR gene mutations are associated with improved OS in PDAC patients treated with FOLFIRINOX.

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Section: Study Population and Patient Selectionmentioning

confidence: 99%

Germline and Somatic DNA Damage Repair Gene Mutations and Overall Survival in Metastatic Pancreatic Adenocarcinoma Patients Treated with FOLFIRINOX

Sehdev

Gbolahan

Hancock

et al. 2018

Clinical Cancer Research

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“…Complementary molecular assays should be considered to analyze tumor response at molecular level in our future investigations. In clinical practice, microbubble-assisted ultrasound is compatible with current administration of Nab-paclitaxel-based chemotherapy protocols 4,48 . This method should be able to increase bioavailability of paclitaxel in the tumor interstitial compartment and to improve its therapeutic effectiveness while minimizing its systemic toxicity (Figure 5) 49,50 .…”

Section: Discussionmentioning

confidence: 99%

Enhancing Nab-Paclitaxel Delivery Using Microbubble-Assisted Ultrasound in a Pancreatic Cancer Model

et al. 2019

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The combination of microbubbles and ultrasound is an emerging method for non-invasive and targeted enhancement of anticancer drugs uptake. This method showed to increase local drug extravasation in tumor tissue while reducing the systemic adverse effects in various tumor models. The present study aims into evaluating the therapeutic efficacy of this approach both in-vitro and in-vivo for Nab-paclitaxel delivery in a pancreatic tumor model. Ultrasound and microbubbles of different types in combination with Nab-paclitaxel showed a significant decrease in cell viability of human pancreatic cancer cells in comparison with Nab-paclitaxel treatment alone in in-vitro scenario. In-vivo, the results demonstrated that ultrasound and microbubbles in combination with Nab-paclitaxel induced a significant decrease in tumor growth in subcutaneous pancreatic adenocarcinoma xenograft model in nude mice in comparison to tumors treated with Nab-paclitaxel alone. The post-mortem anatomopathological analyses of tumor tissues partially confirmed these results. In conclusion, this study demonstrates that microbubble-assisted ultrasound is a promising method to improve the therapeutic efficacy of Nab-paclitaxel in a pancreatic cancer model.

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“…Treatment results for PC are improving due to advances in surgical procedures, neoadjuvant chemotherapy (32)(33)(34)(35)(36) and adjuvant chemotherapy (2-4). However, PC recurs in many patients, and the prognosis after pancreatic surgery is still poor (2)(3)(4)11).…”

Section: Discussionmentioning

confidence: 99%

Feasibility of Combination Therapy with Nab-paclitaxel Plus Gemcitabine in Patients with Recurrent Pancreatic Cancer

et al. 2018

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Background/Aim: Nab-paclitaxel plus gemcitabine (nab-P+Gem) is one of most reliable and effective regimens for borderline or unresectable pancreatic cancer (PC). However, the feasibility and clinical benefits of this regimen have never been evaluated for patients with recurrent PC after pancreatectomy. The aim of this study was to investigate the feasibility of combination therapy with nab-paclitaxel plus gemcitabine (nab-P+Gem) for patients with recurrent PC. Patients and Methods: Twenty-two patients with recurrent PC received an intravenous infusion of nab-P (125 mg/m 2) and Gem (1,000 mg/m 2) on days 1, 8, and 15 of a 4-week cycle. The primary end-point of this study was completion of the 4 cycles. The secondary endpoints were the safety, efficacy, and disease control rate. Results: The treatment completion rate of the 4 cycles was 90.9%. The objective response rate was 13.6% and the disease control rate was 63.6%. The median progression-free survival was 7.2 months. The most common grade 3 or higher hematological toxicity was neutropenia (72.7%). There was no treatment-related death. Furthermore, the chemotherapeutic effects varied with the time of recurrence. Conclusion: Combination nab-P+Gem therapy was welltolerated and effective in patients with recurrent PC. Pancreatic cancer (PC) is the seventh most common cause of cancer-related mortality worldwide (1) and surgical resection is the only potential cure. However, even when curative surgery is performed, the prognosis after pancreatic surgery is poor (2). Currently, adjuvant chemotherapy is considered to be the standard strategy for patients with macroscopicallyresected PC, based on several randomized controlled studies (2-4). However, most patients with relatively advanced disease experience recurrence after macroscopically curative surgical resection with post-operative adjuvant chemotherapy (5-8), and the 5-year survival rate is 12-19% (9-11). Therefore, an optimal treatment for recurrent disease is required. Recently, the efficacy of several chemotherapeutic regimens has been demonstrated for borderline or unresectable PC (12, 13). Among them, nanoparticle albumin-bound (nab)-paclitaxel plus gemcitabine (nab-P+Gem) is one of most reliable and effective regimens (12, 13). However, the feasibility and clinical benefits of this intensive regimen have never been fully evaluated for patients with recurrent PC in weak physical condition after pancreatectomy. The purpose of this study was to assess the safety and efficacy of combination nab-P +Gem therapy in patients with recurrent PC. Patients and Methods Patients. Twenty-two patients with recurrent PC after radical surgery were treated at our hospital from January 2016 to November 2017. The main treatment regimen of adjuvant chemotherapy was orally administered S-1 (TS-1, Taiho Pharmaceutical, Tokyo, Japan), 40 mg, 50 mg or 60 mg according to body-surface area twice a day for 28 days followed by a 14-day rest (1 cycle) for up to 4 cycles (4), while 2 patients received intravenous gemcitabine, 1000 mg/m 2 ,...

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Impact of nab-paclitaxel-based second-line chemotherapy on the outcomes of pancreatic cancer.

Cited by 8 publications

References 0 publications

Germline and Somatic DNA Damage Repair Gene Mutations and Overall Survival in Metastatic Pancreatic Adenocarcinoma Patients Treated with FOLFIRINOX

Germline and Somatic DNA Damage Repair Gene Mutations and Overall Survival in Metastatic Pancreatic Adenocarcinoma Patients Treated with FOLFIRINOX

Enhancing Nab-Paclitaxel Delivery Using Microbubble-Assisted Ultrasound in a Pancreatic Cancer Model

Feasibility of Combination Therapy with Nab-paclitaxel Plus Gemcitabine in Patients with Recurrent Pancreatic Cancer

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