scholarly journals 2207

2017 ◽  
Vol 1 (S1) ◽  
pp. 32-33
Author(s):  
Jacob Ezra Shabason ◽  
Jerry Chen ◽  
Smith Apisarnthanarax ◽  
Nevena Damjanov ◽  
Bruce Giantonio ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Median Survival ◽  
Phase 1 ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer ◽  
Fractionated Radiotherapy ◽  
Grade 3

OBJECTIVES/SPECIFIC AIMS: Patients with locally advanced pancreatic cancer typically have poor outcomes, with a median survival of ~16 months. Novel methods to improve local control are needed. Nab-paclitaxel (abraxane) has shown efficacy in pancreatic cancer and is FDA approved for metastatic disease in combination with gemcitabine. Nab-paclitaxel is also a promising radiosensitizer based on laboratory studies, but it has never been clinically tested with definitive radiotherapy for locally advanced disease. METHODS/STUDY POPULATION: We performed a phase 1 study using a 3+3 dose-escalation strategy to determine the safety and tolerability of dose escalated nab-paclitaxel with fractionated radiotherapy for patients with unresectable or borderline resectable pancreatic cancer. Following induction chemotherapy with 2 cycles of nab-paclitaxel and gemcitabine, patients were treated with weekly nab-paclitaxel and daily radiotherapy to a dose of 52.5 Gy in 25 fractions. Final dose-limiting toxicity (DLT) determination was performed at day 65 after the start of radiotherapy. RESULTS/ANTICIPATED RESULTS: Nine patients received nab-paclitaxel at a dose level of either 100 mg/m2 (n=3) or 125 mg/m2 (n=6). One DLT (grade 3 neuropathy) was observed in a patient who received 125 mg/m2 of nab-paclitaxel. Other grade 3 toxicities included fatigue (11%), anemia (11%), and neutropenia (11%). No grade 4 toxicities were observed. With a median follow-up of 8 months (range 5–28 months), median survival was 19 months and median progression-free survival was 10 months. Following chemoradiation, 3 patients underwent surgical resection, all with negative margins and limited tumor viability. Of the 3 patients, 2 initially had borderline resectable tumors and 1 had an unresectable tumor. Tumor (SMAD-4, Caveolin-1) and peripheral (circulating tumor cells and microvesicles) biomarkers were collected and are being analyzed. DISCUSSION/SIGNIFICANCE OF IMPACT: The combination of fractionated radiation and weekly nab-paclitaxel was safe and well tolerated. This regimen represents a potentially promising therapy for patients with unresectable and borderline resectable pancreatic cancer and warrants further investigation.

Management of Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma

2019 ◽  
Author(s):  
Francis Igor Macedo ◽  
Danny Yakoub ◽  
Vikas Dudeja ◽  
Nipun B. Merchant
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Therapy ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
The United States ◽  
Locally Advanced Pancreatic Cancer ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer ◽  
Number Of Patients

The incidence of pancreatic cancer continues to rise, and it is now the third-leading cause of cancer-related deaths in the United States. Only 15 to 20% of patients are eligible to undergo potentially curative resection, as most tumors are deemed unresectable at the time of diagnosis because of either locally advanced disease or distant metastases. Improvements in preoperative CT imaging have enabled better determination of the extent of disease and allowed for better operative planning. Based on their relationship to the surrounding vasculature and structures and presence or absence of distant disease, pancreatic tumors are classified into four categories: resectable, borderline resectable pancreatic cancer (BRPC), locally advanced pancreatic cancer (LAPC), and metastatic. With the recent advent of more effective chemotherapy regimens, efforts have focused on using neoadjuvant therapy approaches to increase the likelihood of achieving an R0 in patients with BRPC and possibly convert unresectable, locally advanced tumors to potentially resectable tumors. Response with neoadjuvant therapy regimens has resulted in increased number of patients eligible for resection, many times requiring vascular resection. Herein, we describe recent changes in the classification, important surgical and pathologic considerations and updated multimodal therapeutic options in the complex management of BRPC and LAPC.  This review contains 5 figures, 2 tables, and 78 references. Key Words: borderline resectable pancreatic cancer, CA 19-9, FOLFIRINOX, locally advanced pancreatic cancer, nab-paclitaxel, neoadjuvant chemotherapy, pancreatectomy, portal vein resection, radiation therapy, gemcitabine

Management of Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma

2019 ◽  
Author(s):  
Francis Igor Macedo ◽  
Danny Yakoub ◽  
Vikas Dudeja ◽  
Nipun B. Merchant
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Therapy ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
The United States ◽  
Locally Advanced Pancreatic Cancer ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer ◽  
Number Of Patients

The incidence of pancreatic cancer continues to rise, and it is now the third-leading cause of cancer-related deaths in the United States. Only 15 to 20% of patients are eligible to undergo potentially curative resection, as most tumors are deemed unresectable at the time of diagnosis because of either locally advanced disease or distant metastases. Improvements in preoperative CT imaging have enabled better determination of the extent of disease and allowed for better operative planning. Based on their relationship to the surrounding vasculature and structures and presence or absence of distant disease, pancreatic tumors are classified into four categories: resectable, borderline resectable pancreatic cancer (BRPC), locally advanced pancreatic cancer (LAPC), and metastatic. With the recent advent of more effective chemotherapy regimens, efforts have focused on using neoadjuvant therapy approaches to increase the likelihood of achieving an R0 in patients with BRPC and possibly convert unresectable, locally advanced tumors to potentially resectable tumors. Response with neoadjuvant therapy regimens has resulted in increased number of patients eligible for resection, many times requiring vascular resection. Herein, we describe recent changes in the classification, important surgical and pathologic considerations and updated multimodal therapeutic options in the complex management of BRPC and LAPC.  This review contains 5 figures, 2 tables, and 78 references. Key Words: borderline resectable pancreatic cancer, CA 19-9, FOLFIRINOX, locally advanced pancreatic cancer, nab-paclitaxel, neoadjuvant chemotherapy, pancreatectomy, portal vein resection, radiation therapy, gemcitabine

Toxicity study of gemcitabine, oxaliplatin, and bevacizumab followed by 5-fluorouracil, oxaliplatin, bevacizumab, and radiotherapy in patients with locally advanced pancreatic cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 337-337 ◽  
Author(s):  
Davendra Sohal ◽  
James M. Metz ◽  
Weijing Sun ◽  
Kathleen Harlacker ◽  
Bruce J. Giantonio ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Median Survival ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer ◽  
Borderline Resectable ◽  
Surgical Options ◽  
Grade 3 ◽  
Cancer Experience ◽  
Entire Treatment

337 Background: Patients with advanced pancreatic cancer experience higher response rates (though not always improved survival) with combinations of either platinum compounds or bevacizumab in combination with gemcitabine. In patients with locally advanced pancreatic cancer, improved response affects local control and surgical options. Methods: We piloted a three-drug combination of gemcitabine/oxaliplatin/5-FU/bevacizumab Q2w for four cycles, followed by oxaliplatin (85 mg/m2/q2w) and bevacizumab (5 mg/kg q2w) added to infusional 5-FU and radiation, in patients with pancreatic cancer that was unresectable or borderline resectable. Results: Nineteen patients have been treated, of whom 17 received the entire treatment. Median age was 60, with 12 women and 7 men. Stages were: one IIA, one IIB, and 17 III. Sixteen were unresectable and 3 borderline resectable by protocol-specified criteria. Major toxicities during chemotherapy were: grade 3 neutropenia (5/19); grade 2 neutropenia (7/19), anemia (2/19), thrombocytopenia (2/19). During chemoradiation major toxicities were: grade 3 nausea (3/19), vomiting (3/19), leukopenia (2/19); grade 2 nausea (5/19), leukopenia (4/19). One patient had grade 3 pulmonary embolism that led to withdrawal from the study. One patient had progressive pain early on; no other disease progression was noted during treatment. Five patients (3 inoperable, 2 borderline) went on to have surgery. Median survival was 14 months (range 3 to 40+). For the 5 patients who had surgery, median survival was 17.1 months (range 9.5 to 40+). Conclusions: We conclude that this regimen is well-tolerated by patients with locally advanced pancreatic cancer, and that the therapeutic results support further evaluation. Additional correlative studies are underway to identify characteristics associated with a favorable outcome.

Accelerated fraction radiotherapy with concomitant capecitabine as neoadjuvant therapy of borderline resectable pancreatic cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 329-329 ◽  
Author(s):  
Samhita Chakraborty ◽  
Todd W. Bauer ◽  
Monica M Morris ◽  
Erin Yarde ◽  
J Thomas Parsons ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Molecular Mechanisms ◽  
Palliative Therapy ◽  
External Beam Radiation ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Beam Radiation ◽  
Early Stage Disease ◽  
Borderline Resectable Pancreatic Cancer ◽  
Grade 3

329 Background: Surgical therapy remains the only curative modality for pancreatic cancer, though survival remains quite poor even for patients with resected early stage disease. Better (neo) adjuvant therapies are needed to improve resectability rates for patients with borderline resectable pancreatic cancer and to prevent recurrence following resection. We undertook this pilot study to determine the safety of accelerated fraction radiotherapy (AFRT) with capecitabine in such patients. Methods: Eligible patients have histologically confirmed borderline resectable adenocarcinoma of the pancreas as defined by the MD Anderson categories of vascular involvement, indeterminate metastatic disease, borderline performance status; normal organ function; and no prior therapy for pancreatic cancer. Radiation is given as external beam radiation therapy to a dose of 50 Gy delivered in 20, 2.5 Gy fractions Mon-Fri using IMRT. If insurance denied IMRT, 3D conformal techniques with daily image guidance is permitted. Capecitabine is delivered as 825mg/m2 BID on radiation days. The primary outcome is to determine the frequency of treatment-related adverse events (AE). Planned enrollment is 40 pts. Results: 10 pts have enrolled to date. 8/10 received IMRT. This regimen has been exceedingly tolerable. Lymphopenia is the most common AE (n=10), grade 3-4 n=6. Other common toxicities were hyponatremia (n=6), fatigue (n=5). Grade 3 AE occurred in 8 pts, grade 4 in 3 patients. One pt had hemorrhage from a radiation induced gastric ulcer complicated by an MI. 5/10 pts had stable disease and were resected and 4/5 had an R0 resection. In the remaining 5/10 patients, disease progressed outside the pancreas and they are receiving palliative therapy. Conclusions: The combination of AFRT and capecitabine was well tolerated. Xenograft models derived from these patients’ tumors are being used to study molecular mechanisms of treatment resistance that could be targeted in a follow up phase II study building on this platform.

Phase I Trial of the Human Immunodeficiency Virus Protease Inhibitor Nelfinavir and Chemoradiation for Locally Advanced Pancreatic Cancer

2008 ◽  
Vol 26 (16) ◽  
pp. 2699-2706 ◽  
Author(s):  
Thomas B. Brunner ◽  
Matthias Geiger ◽  
Gerhard G. Grabenbauer ◽  
Marga Lang-Welzenbach ◽  
Tine S. Mantoni ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Peritoneal Metastasis ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Hiv Protease ◽  
Hiv Protease Inhibitors ◽  
Borderline Resectable ◽  
Stent Occlusion ◽  
Positron Emission ◽  
Grade 3

PurposePreclinically, HIV protease inhibitors radiosensitize tumors with activated PI3-kinase/Akt pathway. We determined the toxicity of nelfinavir chemoradiotherapy in borderline resectable and unresectable pancreatic cancer.Patients and MethodsOral nelfinavir (2 × 1,250 mg) was started 3 days before and continued throughout chemoradiotherapy to 50.4 Gy (boost, 59.4 Gy) in 12 patients. Two gemcitabine dose levels (DL) were tested (200 mg/m2and 300 mg/m2on days 1, 8, 22, and 29). Cisplatin was administered on the same days at 30 mg/m2. Phospho-Akt downregulation by nelfinavir was monitored by immunoblotting in patient leukocytes. Restaging positron emission tomography (PET)/computed tomography (CT) and CA19-9 levels served to assess response, and responding tumors were resected.ResultsAt each DL, five of six patients completed chemoradiotherapy, and two of 12 patients had incomplete chemoradiotherapy because of clinical depression (DL1) and peritoneal metastasis (DL2). Grade 4 toxicities were a transaminase elevation (DL2) as a result of biliary stent occlusion and acute cholecystitis as a result of peritoneal metastasis (DL2). Stent occlusions led to dose-limiting toxicities of grade 3 liver enzyme and bilirubin elevations (two patients at DL1, one patient at DL2). Grade 3 nausea and vomiting occurred in a DL2 patient, and weight loss occurred in a DL1 patient who refused supportive feeding. Secondary complete resection was possible in six of 10 patients with complete chemoradiotherapy, including one tumor with pathologic sterilization. Partial CT responses were observed in five of 10 patients who completed chemoradiotherapy. Of nine patients assessable by PET,responses were complete in five patients and partial patients, and stable disease was observed in two patients.ConclusionThe combination of nelfinavir and chemoradiotherapy showed acceptable toxicity and promising activity in patients with pancreatic cancer.

Sign in / Sign up

Export Citation Format

Share Document