Neoadjuvant therapy with nanoparticle albumin-bound (nab)-paclitaxel to enhance the resectability of locally advanced pancreatic cancer (LAPC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14644-e14644
Author(s):  
Prasad Cooray ◽  
Andrew Peter Dean
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Therapy ◽  
Surgical Resection ◽  
Median Survival ◽  
Adjuvant Treatment ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Cancer Recurrence ◽  
Stage Iv ◽  
Borderline Resectable

e14644 Background: Resection offers the only probability of cure for pancreatic adenocarcinoma but only a minority have resectable disease at diagnosis. Effective neo-adjuvant therapy for LAPC could down-size the tumor rendering it resectable. Neo-adjuvant therapy may retard cancer dissemination thought to occur early in pancreatic cancer. The aim of this study was to retrospectively evaluate if neo-adjuvant treatment with nab-paclitaxel in patients with LAPC could result in tumor down-sizing to allow resection and improve outcomes. Methods: Data was collected from the medical records of pancreatic cancer patients who presented to two clinics from 06/2009 to 12/2011 and were treated with nab-paclitaxel (n = 63). Resectability was assessed by review of imaging by the radiologist and the treating surgeon. Twenty three of 63 patients had LAPC and 40/63 had stage IV disease. Of the LAPC patients, 8/23 (35%) were classified as borderline resectable (BR) and 15/23 (65%) were classified as unresectable (UR). Patients received nab-paclitaxel (100-125 mg/m2 D1,8,15) in combination with gemcitabine or carboplatin. The BR/UR patients (n=23) received a median 5 cycles of chemotherapy. They were re-evaluated for suitability for surgical resection. Results: Following neo-adjuvant treatment, 16/23 (69%) had a radiological PR and 17/23 (74%) had a major biochemical response (defined as >70% decline in Ca19.9 level). A total of 6/23 patients (26%) were then able to undergo surgical resection, with resections planned for further 2/23 (8%) patients.Of the 6 resected patients, 4 had R0 resections and 2 had R1 resection. After a median follow up of 18 months, all 6 resected patients are alive and 4 of them remain free of cancer recurrence. The median survival for patients who remained unresectable (15/23) was 9 months. The median survival for converted patients (6/23) has not yet reached. Conclusions: These results suggest that a subgroup of patients with LAPC could be converted to a resectable stage with the use of nab-paclitaxel as neo-adjuvant therapy. Such converted patients may enjoy durable improved outcomes and this approach warrants further investigation in a phase II clinical trial.

Adjuvant and Neoadjuvant Therapy for Pancreatic Adenocarcinoma

2017 ◽  
Author(s):  
Gregory C Wilson ◽  
Brent T Xia ◽  
Syed A Ahmed
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Therapy ◽  
Neoadjuvant Therapy ◽  
Pancreatic Adenocarcinoma ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Pancreatic Cancer ◽  
Treatment Strategies ◽  
Ductal Adenocarcinoma ◽  
Borderline Resectable

Despite decades of advancement and research into the multimodal care of pancreatic cancer, mortality after the diagnosis of pancreatic ductal adenocarcinoma remains grim. The role of adjuvant therapy following surgical resection has been well established in the literature. However, adjuvant therapy is imperfect, and outside of a clinical trial, there are high rates of omission or delayed initiation of therapy. Neoadjuvant treatment strategies continue to be explored in the management of resectable, borderline-resectable, and locally advanced unresectable pancreatic adenocarcinoma. With improved resection rates and the possibility for tumor downstaging, neoadjuvant therapy has become standard for patients with borderline-resectable and locally advanced unresectable tumors. Additional benefits of neoadjuvant therapy in the treatment of resectable tumors include improved completion rates of systemic therapy and R0 resection rates. Future clinical trials, including the use of novel treatment agents and combination treatment strategies in both neoadjuvant and adjuvant regimens, will add value to the treatment of pancreatic adenocarcinoma. Key words: adjuvant therapy, borderline-resectable pancreatic cancer, locally advanced pancreatic cancer, neoadjuvant therapy, pancreatic adenocarcinoma, resectable disease 

Adjuvant and Neoadjuvant Therapy for Pancreatic Adenocarcinoma

2017 ◽  
Author(s):  
Gregory C Wilson ◽  
Brent T Xia ◽  
Syed A Ahmed
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Therapy ◽  
Neoadjuvant Therapy ◽  
Pancreatic Adenocarcinoma ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Pancreatic Cancer ◽  
Treatment Strategies ◽  
Ductal Adenocarcinoma ◽  
Borderline Resectable

Despite decades of advancement and research into the multimodal care of pancreatic cancer, mortality after the diagnosis of pancreatic ductal adenocarcinoma remains grim. The role of adjuvant therapy following surgical resection has been well established in the literature. However, adjuvant therapy is imperfect, and outside of a clinical trial, there are high rates of omission or delayed initiation of therapy. Neoadjuvant treatment strategies continue to be explored in the management of resectable, borderline-resectable, and locally advanced unresectable pancreatic adenocarcinoma. With improved resection rates and the possibility for tumor downstaging, neoadjuvant therapy has become standard for patients with borderline-resectable and locally advanced unresectable tumors. Additional benefits of neoadjuvant therapy in the treatment of resectable tumors include improved completion rates of systemic therapy and R0 resection rates. Future clinical trials, including the use of novel treatment agents and combination treatment strategies in both neoadjuvant and adjuvant regimens, will add value to the treatment of pancreatic adenocarcinoma. Key words: adjuvant therapy, borderline-resectable pancreatic cancer, locally advanced pancreatic cancer, neoadjuvant therapy, pancreatic adenocarcinoma, resectable disease 

Single institution experience of chemoradiation with gemcitabine versus capecitabine in borderline resectable and locally advanced pancreatic cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14659-e14659
Author(s):  
Adam S. Kotowski ◽  
Naveen Yarlagadda ◽  
Kilian Salerno May ◽  
Graham Walter Warren ◽  
Boris W. Kuvshinoff ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Surgical Resection ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Resection Rate ◽  
Borderline Resectable ◽  
Pathology Laboratory

e14659 Background: To retrospectively evaluate the outcome of borderline resectable (BR) and locally advanced unresectable (LA) pancreatic cancer patients treated with concurrent chemoradiotherapy (CRT) with gemcitabine (G) or capecitabine (C). Methods: Retrospective chart review of patients treated between August 2005 and September 2011 generated 30 BR and 40 LA pts. Cases were analyzed for patient and treatment characteristics including age, gender, weight loss, ECOG PS, albumin, stage, grade, location, pathology, laboratory values, chemotherapy (CT) regimens, radiotherapy dose and technique, and toxicity using CTCAE v.4.0. Endpoints evaluated were surgical resection rate, progression free survival (PFS), and median overall survival (mOS). Results: Patient characteristics were comparable between CRT/G and CRT/C in both BR and LA patients. Gemcitabine iv 300mg/m2 weekly or capecitabine po 825mg/m2 BID were used during CRT. Among BR patients who received CRT (n=21), 17 (56.6%) received CRT/G, 4 (13.3%) CRT/C, and others received CT alone. For BR, surgical resection was performed in 52.9% of CRT/G patients. The PFS were 17.4 months (m) and 4.8m (p=0.009), and mOS were 21.9m and 5.7m (p=0.004) for CRT/G and CRT/C respectively. For LA patients who received CRT (n=25), 18% of CRT/G underwent surgical resection and none of CRT/C did. The PFS 8.4m and 10.4m (p=0.63) and mOS were 14.9m and 11.5m (p=0.11) for CRT/G and CRT/C respectively. Comparing CRT and CT groups, mOS were not significantly different for LA patients, and longer for BR patients (14.4m vs. 5.5m) although this is likely due to confounding factors such as physician preference and patient selection. No significant differences were noted for grade 3/4 toxicities between both CRT groups. Conclusions: In this series, CRT/G in both BR and LA setting were associated with a high surgical resection rate with acceptable toxicity and potentially improved survival for patients not felt to be surgical candidates at presentation. These data warrant validation in larger prospective randomized studies.

Neoadjuvant FOLFIRINOX and/or gemcitabine/nab-paclitaxel for advanced pancreatic adenocarcinoma.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 473-473 ◽  
Author(s):  
Keli Turner ◽  
Sumana Narayanan ◽  
Kristopher Attwood ◽  
Steven N. Hochwald ◽  
Renuka V. Iyer ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Neoadjuvant Therapy ◽  
Surgical Resection ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
R0 Resection ◽  
Borderline Resectable ◽  
Biomarker Response

473 Background: Neoadjuvant chemotherapy is increasingly being utilized for locally advanced (LAPC)/borderline resectable pancreatic cancer (BRPC); however, long term follow up data is sparse. At our institution, we use FOLFIRINOX as the regimen of choice. Gemcitabine (Gem) and nab-Paclitaxel (Abraxane) is utilized in patients not suited for FOLFIRINOX or if they have poor radiographic response and/or develop significant toxicities to FOLFIRINOX. The aim of this study was to report our institutional experience with neoadjuvant therapy for patients with advanced pancreatic cancer. Methods: A retrospective review was performed of all patients with BRPC or LAPC who received FOLFIRINOX (or a modified regimen), Gem/nab-Paclitaxel, or both prior to surgical resection. FOLFIRINOX was typically given for 4 – 6 cycles while gem/nab-Paclitaxel was given for 2 cycles. Results: From January 2011 to December 2015, 39 patients were identified who met the study criteria. Eight patients received FOLFIRINOX alone (median age 62), 20 patients received FOLFIRINOX + Gem/nab-Paclitaxel, and 11 received only Gem/nab-Paclitaxel (median age 72). Eighteen patients (46%) completed the intended cycles of chemotherapy. Twenty two patients had a radiologic and/or biomarker response. Exploration was performed in 25 of 39 (64%) patients of whom 20 (51%) underwent curative resection. Of the 20 resected patients, there were no post-operative deaths. The median tumor size, median lymph node ratio, and R0 resection rates were 2.4 cm, 0, and 85% for the entire cohort. Median follow up was 20.7 months. The median overall survival for the resected cohort was not reached vs 13.5 months in the no resection group; two year overall survival for the resection vs. no resection groups was 87% vs 16% (p < .001). Conclusions: FOLFIRINOX and/or Gemcitabine/nab-Paclitaxel as neoadjuvant therapy for LAPC/BRPC is fairly well tolerated, leads to appreciable rates of margin negative surgical resection, and a significant overall survival advantage.

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.

scholarly journals Neoadjuvant Chemotherapy Switch in Borderline Resectable/Locally Advanced Pancreatic Cancer

2021 ◽  
Author(s):  
Roberto Alva-Ruiz ◽  
Lavanya Yohanathan ◽  
Jennifer A. Yonkus ◽  
Amro M. Abdelrahman ◽  
Lindsey A. Gregory ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Surgical Resection ◽  
Locally Advanced ◽  
Multivariable Analysis ◽  
Advanced Pancreatic Cancer ◽  
Preoperative Treatment ◽  
Borderline Resectable ◽  
Curative Intent ◽  
Chemotherapeutic Regimen

Abstract Background Neoadjuvant chemotherapy (NAC) is an integral part of preoperative treatment for patients with borderline resectable/locally advanced (BR/LA) pancreatic ductal adenocarcinoma (PDAC). The identification of a chemotherapeutic regimen that is both effective and tolerable is critical for NAC to be of oncologic benefit. After initial first-line (FL) NAC, some patients have lack of response or therapeutic toxicities precluding further treatment with the same regimen; optimal decision making regarding this patient population is unclear. Chemotherapy switch (CS) may allow for a larger proportion of patients to undergo curative-intent resection after NAC. Methods We reviewed our surgical database for patients undergoing combinatorial NAC for BR/LA PDAC. Variant histologic exocrine carcinomas, intraductal papillary mucinous neoplasm-associated PDAC, and patients without research consent were excluded. Results Overall, 468 patients with BR/LA PDAC receiving FL chemotherapy were reviewed, of whom 70% (329/468) continued with FL chemotherapy followed by surgical resection. The remaining 30% (139/468) underwent CS, with 72% (100/139) of CS patients going on to curative-intent surgical resection. Recurrence-free survival (RFS) and overall survival (OS) were not significantly different between the resected FL and CS cohorts (30.0 vs. 19.1 months, p = 0.13, and 41.4 vs. 36.4 months, p = 0.94, respectively) and OS was significantly worse in those undergoing CS without subsequent resection (19 months, p < 0.0001). On multivariable analysis, carbohydrate antigen (CA) 19-9 and pathologic treatment responses were predictors of RFS and OS. Conclusion CS in patients undergoing NAC for BR/LA pancreatic cancer does not incur oncologic detriment. The incorporation of CS into NAC treatment sequencing may allow a greater proportion of patients to proceed to curative-intent surgery.

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.

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