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Pancreatic Neoplasms: HELP
Articles by Andrew H. Ko
Based on 47 articles published since 2010
(Why 47 articles?)

Between 2010 and 2020, A. H. Ko wrote the following 47 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Pancreatic Adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. 2017

Tempero, Margaret A / Malafa, Mokenge P / Al-Hawary, Mahmoud / Asbun, Horacio / Bain, Andrew / Behrman, Stephen W / Benson, Al B / Binder, Ellen / Cardin, Dana B / Cha, Charles / Chiorean, E Gabriela / Chung, Vincent / Czito, Brian / Dillhoff, Mary / Dotan, Efrat / Ferrone, Cristina R / Hardacre, Jeffrey / Hawkins, William G / Herman, Joseph / Ko, Andrew H / Komanduri, Srinadh / Koong, Albert / LoConte, Noelle / Lowy, Andrew M / Moravek, Cassadie / Nakakura, Eric K / O'Reilly, Eileen M / Obando, Jorge / Reddy, Sushanth / Scaife, Courtney / Thayer, Sarah / Weekes, Colin D / Wolff, Robert A / Wolpin, Brian M / Burns, Jennifer / Darlow, Susan. · ·J Natl Compr Canc Netw · Pubmed #28784865.

ABSTRACT: Ductal adenocarcinoma and its variants account for most pancreatic malignancies. High-quality multiphase imaging can help to preoperatively distinguish between patients eligible for resection with curative intent and those with unresectable disease. Systemic therapy is used in the neoadjuvant or adjuvant pancreatic cancer setting, as well as in the management of locally advanced unresectable and metastatic disease. Clinical trials are critical for making progress in treatment of pancreatic cancer. The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis and treatment with systemic therapy, radiation therapy, and surgical resection.

2 Guideline Pancreatic Adenocarcinoma, version 2.2012: featured updates to the NCCN Guidelines. 2012

Tempero, Margaret A / Arnoletti, J Pablo / Behrman, Stephen W / Ben-Josef, Edgar / Benson, Al B / Casper, Ephraim S / Cohen, Steven J / Czito, Brian / Ellenhorn, Joshua D I / Hawkins, William G / Herman, Joseph / Hoffman, John P / Ko, Andrew / Komanduri, Srinadh / Koong, Albert / Ma, Wen Wee / Malafa, Mokenge P / Merchant, Nipun B / Mulvihill, Sean J / Muscarella, Peter / Nakakura, Eric K / Obando, Jorge / Pitman, Martha B / Sasson, Aaron R / Tally, Anitra / Thayer, Sarah P / Whiting, Samuel / Wolff, Robert A / Wolpin, Brian M / Freedman-Cass, Deborah A / Shead, Dorothy A / Anonymous5390728. ·UCSF Helen Diller Family Comprehensive Cancer Center. ·J Natl Compr Canc Netw · Pubmed #22679115.

ABSTRACT: The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pancreatic Adenocarcinoma discuss the workup and management of tumors of the exocrine pancreas. These NCCN Guidelines Insights provide a summary and explanation of major changes to the 2012 NCCN Guidelines for Pancreatic Adenocarcinoma. The panel made 3 significant updates to the guidelines: 1) more detail was added regarding multiphase CT techniques for diagnosis and staging of pancreatic cancer, and pancreas protocol MRI was added as an emerging alternative to CT; 2) the use of a fluoropyrimidine plus oxaliplatin (e.g., 5-FU/leucovorin/oxaliplatin or capecitabine/oxaliplatin) was added as an acceptable chemotherapy combination for patients with advanced or metastatic disease and good performance status as a category 2B recommendation; and 3) the panel developed new recommendations concerning surgical technique and pathologic analysis and reporting.

3 Editorial Achieving the best of both worlds. 2013

Ko, Andrew H / Cella, David. · ·J Clin Oncol · Pubmed #23213099.

ABSTRACT: -- No abstract --

4 Review Clinical Management: Metastatic Disease. 2017

Ko, Andrew H. ·From the Division of Hematology/Oncology, University of California, San Francisco, CA. ·Cancer J · Pubmed #29189332.

ABSTRACT: Most patients with pancreatic cancer either present with or eventually develop metastatic disease during the course of their illness. For such individuals, systemic therapy, namely, cytotoxic therapy, represents the mainstay of treatment and is administered with noncurative intent. Of the various chemotherapy options now available for treating metastatic pancreatic cancer, 2 combination regimens, FOLFIRINOX (infusional 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) and the doublet of gemcitabine and albumin-bound paclitaxel, have emerged as frontline standards of care, based on phase III studies demonstrating a significant survival benefit compared with single-agent gemcitabine. More patients are also now able to be sequenced through 2 or more lines of treatment, with newer regimens such as nanoliposomal irinotecan plus infusional 5-fluorouracil and leucovorin receiving US Food and Drug Administration approval specifically for use in this second-line setting. Selection of therapies remains primarily guided by clinical considerations, particularly performance status, as well as age, comorbid medical conditions, and organ and bone marrow function. In contrast, molecular predictors of efficacy and toxicity have not yet been validated in this disease context. Areas of novel therapeutic development include targeting the stromal microenvironment, exploring combinations of immunotherapeutic agents, and identifying molecular subsets of metastatic pancreatic cancer that may uniquely susceptible to specific strategies, such as hampering DNA damage repair.

5 Review Best practices for the treatment of metastatic pancreatic adenocarcinoma: the therapeutic landscape in 2017. 2017

Cinar, Pelin / Ko, Andrew H. ·Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, USA. · Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, USA. pelin.cinar@ucsf.edu. ·Chin Clin Oncol · Pubmed #28705006.

ABSTRACT: The vast majority of patients diagnosed with pancreatic adenocarcinoma have inoperable, most commonly metastatic, disease at the time of initial presentation, at which point systemic therapy becomes the mainstay of treatment. Although survival rates remain very poor in this clinical setting, patients currently have a greater number of therapeutic options available to them than ever before, and consequently individuals are more frequently able to be sequenced through multiple lines of treatment. In this review, we will provide an overview of the current treatment landscape for metastatic pancreatic cancer in 2017, focusing on best practices and the various factors that should be considered in selecting the most appropriate regimen for a given individual. Options for front-line therapy include both infusional 5-fluorouracil, leucovorin, irinotecan, oxaliplatin (FOLFIRINOX) and the combination of gemcitabine plus nab-paclitaxel; however, how to choose between these two regimens can sometimes pose a challenging problem, and some patients may not be suitable candidates for either. For patients who are robust enough to receive second-line therapy (and beyond), the selection of treatment depends in part on their prior treatment exposure; newer drugs such as nanoliposomal irinotecan (nal-IRI) (in combination with infusional 5-fluorouracil and leucovorin) are now approved by the United States Food and Drug Administration (FDA) specifically for use following disease progression on first-line gemcitabine-based therapy. Despite these welcome advances in standard of care treatment, patients should still be encouraged to participate in clinical trials whenever possible.

6 Review Nanomedicine developments in the treatment of metastatic pancreatic cancer: focus on nanoliposomal irinotecan. 2016

Ko, Andrew H. ·Division of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA. ·Int J Nanomedicine · Pubmed #27099488.

ABSTRACT: Nanoliposomal irinotecan (nal-IRI) was originally developed using an efficient and high-loading capacity system to encapsulate irinotecan within a liposomal carrier, producing a therapeutic agent with improved biodistribution and pharmacokinetic characteristics compared to free drug. Specifically, administration of nal-IRI results in prolonged exposure of SN-38, the active metabolite of irinotecan, within tumors, while at the same time offering the advantage of less systemic toxicity than traditional irinotecan. These favorable properties of nal-IRI, confirmed in a variety of tumor xenograft models, led to its clinical evaluation in a number of disease indications for which camptothecins have proven activity, including in colorectal, gastric, and pancreatic cancers. The culmination of these clinical trials was the NAPOLI-1 (Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy) trial, an international Phase III study evaluating nal-IRI both alone and in combination with 5-fluorouracil and leucovorin in patients with metastatic pancreatic adenocarcinoma following progression on gemcitabine-based chemotherapy. Positive results from NAPOLI-1 led to approval of nal-IRI (with 5-fluorouracil/leucovorin) in October 2015 by the US Food and Drug Administration specifically for the treatment of metastatic pancreatic cancer in the second-line setting and beyond, a clinical context in which there had previously been no accepted standard of care. As such, nal-IRI represents an important landmark in cancer drug development, and potentially ushers in a new era where a greater number of patients with advanced pancreatic cancer can be sequenced through multiple lines of therapy translating into meaningful improvements in survival.

7 Review MM-398 (nanoliposomal irinotecan): emergence of a novel therapy for the treatment of advanced pancreatic cancer. 2016

Carnevale, Julia / Ko, Andrew H. ·Division of Hematology & Oncology, University of California San Francisco, San Francisco, CA, USA. ·Future Oncol · Pubmed #26685802.

ABSTRACT: While progress in the treatment of advanced pancreatic cancer has accelerated in recent years, this malignancy continues to have an exceedingly poor prognosis, with no standard of care options beyond front-line chemotherapy. Currently, there are a number of new therapeutic agents in varying stages of clinical development, including molecularly targeted agents, immunotherapies, and modified versions of cytotoxics. MM-398, a novel nanoliposomal formulation of irinotecan, was designed to maximize tumor exposure while minimizing systemic toxicity due to its favorable pharmacokinetic profile. Overall, across multiple clinical trials in multiple disease indications, MM-398 has been shown to have a favorable safety and tolerability profile compared with standard irinotecan. Recent results of the Phase III NAPOLI-1 trial in patients with metastatic pancreatic cancer refractory to gemcitabine-based chemotherapy have shown a significant improvement in overall survival of MM-398 when combined with 5-fluorouracil/leucovorin, compared with 5-fluorouracil/leucovorin alone. This review focuses on the development and pharmacokinetic properties of MM-398, followed by evaluation of its safety and efficacy with a primary emphasis on clinical trials in advanced pancreatic cancer.

8 Review Treatment Approaches to Locally Advanced Pancreatic Adenocarcinoma. 2015

Pollom, Erqi L / Koong, Albert C / Ko, Andrew H. ·Department of Radiation Oncology, Stanford Cancer Center, Stanford University, 875 Blake Wilbur Drive, MC5847, Stanford, CA 94305-5847, USA. · Division of Hematology/Oncology, University of California San Francisco, 1600 Divisadero Street, 4th Floor, Box 1705, San Francisco, CA 94115, USA. Electronic address: andrewko@medicine.ucsf.edu. ·Hematol Oncol Clin North Am · Pubmed #26226908.

ABSTRACT: This article focuses on the management of locally advanced pancreatic cancer, which should be treated as a distinct entity separate from metastatic disease and borderline resectable disease. Although the role, timing, and sequencing of radiation relative to systemic therapy in this disease are controversial, an emerging treatment paradigm involves induction chemotherapy, followed by consolidative chemoradiation in patients who do not progress. In addition, new chemotherapy regimens as well as novel radiosensitizers have shown promise and need to be tested further in the locally advanced setting. Advances in radiotherapy have enabled stereotactic body radiotherapy and should continue to be prospectively evaluated.

9 Review Making sense of current and emerging therapies in pancreatic cancer: balancing benefit and value. 2015

Ahn, Daniel H / Ko, Andrew H / Meropol, Neal J / Bekaii-Saab, Tanios S. ·From the The Ohio State University Wexner Medical Center, Columbus, OH; UCSF Helen Diller Comprehensive Cancer Center, San Francisco, CA; University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western University, Cleveland, OH. ·Am Soc Clin Oncol Educ Book · Pubmed #25993177.

ABSTRACT: Pancreatic cancer remains the fourth leading cause of cancer deaths in the United States with a dismal prognosis and a 5-year survival of less than 5% across all stages.(1) In 2014, there were approximately 46,420 new cases of pancreatic cancer with only 9% of patients having localized disease.(2) Given that the vast majority of patients present with advanced disease, much of the focus for drug development has been in the metastatic setting, which is evident with the advent of two combination chemotherapy regimens for this indication. Although conventional cytotoxic chemotherapy remains the standard of care, an ongoing search for novel therapeutic approaches continues. We will highlight several new approaches here, with a particular emphasis on immunotherapeutic strategies. We will also introduce concepts regarding the potential economic effects associated with the development and implementation of new treatments in pancreatic cancer.

10 Review Progress in the treatment of metastatic pancreatic cancer and the search for next opportunities. 2015

Ko, Andrew H. ·From the University of California San Francisco Comprehensive Cancer Center, San Francisco, CA. andrewko@medicine.ucsf.edu. ·J Clin Oncol · Pubmed #25918299.

ABSTRACT: A growing number of therapeutic options are now available for patients with metastatic pancreatic cancer, informed by positive results from recently completed phase III clinical trials. These have led to modest, if not necessarily transformative, improvements in clinical outcomes. Although the standard of care for metastatic disease remains cytotoxic therapy, a variety of novel therapeutic approaches are currently under active investigation, several of which have already demonstrated encouraging results in phase I/II studies. The following three broad categories (with significant overlap among them) are highlighted here: stromal-depleting agents, immunotherapies, and signal transduction inhibitors. The mechanistic rationale, limitations, and promise of each of these strategies specific to pancreatic cancer are discussed, as are the aspects of this disease and this patient population that pose ongoing challenges in terms of both therapeutic management and biomarker-driven trial design.

11 Review Beyond first-line chemotherapy for advanced pancreatic cancer: an expanding array of therapeutic options? 2014

Walker, Evan J / Ko, Andrew H. ·Evan J Walker, Andrew H Ko, University of California, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA 94115, United States. ·World J Gastroenterol · Pubmed #24605022.

ABSTRACT: While an increasing number of therapeutic options are now available for the first-line treatment of locally advanced or metastatic pancreatic cancer, the optimal choice for treatment in the second-line setting and beyond is less well defined. A variety of cytotoxic agents, either alone or in combination, have been evaluated, although primarily in the context of small single-arm or retrospective studies. Most regimens have been associated with median progression-free survival rates in the range of 2-4 mo and overall survival rates between 4-8 mo, highlighting the very poor prognosis of patients who are candidates for such treatment. Targeted therapies studied in this chemotherapy-refractory setting, meanwhile, have produced even worse efficacy results. In the current article, we review the clinical evidence for treatment of refractory disease, primarily in patients who have progressed on front-line gemcitabine-based chemotherapy. In the process, we highlight the limitations of the available data to date as well as some of the challenges in designing appropriate clinical trials in this salvage setting, including how to select an appropriate control arm given the absence of a well-established reference standard, and the importance of incorporating predictive biomarkers and quality of life measures whenever possible into study design.

12 Clinical Trial A Randomized, Double-Blinded, Phase II Trial of Gemcitabine and Nab-Paclitaxel Plus Apatorsen or Placebo in Patients with Metastatic Pancreatic Cancer: The RAINIER Trial. 2017

Ko, Andrew H / Murphy, Patrick B / Peyton, James D / Shipley, Dianna L / Al-Hazzouri, Ahmed / Rodriguez, Francisco A / Womack, Mark S / Xiong, Henry Q / Waterhouse, David M / Tempero, Margaret A / Guo, Shuangli / Lane, Cassie M / Earwood, Chris / DeBusk, Laura M / Bendell, Johanna C. ·Division of Hematology and Oncology, University of California, San Francisco, California, USA andrew.ko@ucsf.edu. · Tennessee Oncology, PLLC/SCRI, Nashville, Tennessee, USA. · Florida Cancer Specialists/SCRI, Fort Myers, Florida, USA. · Tennessee Oncology, PLLC/SCRI, Chattanooga, Tennessee, USA. · The Center for Cancer and Blood Disorders/SCRI, Fort Worth, Texas, USA. · Oncology Hematology Care/SCRI, Cincinnati, Ohio, USA. · Division of Hematology and Oncology, University of California, San Francisco, California, USA. · Sarah Cannon Research Institute (SCRI), Nashville, Tennessee, USA. ·Oncologist · Pubmed #28935773.

ABSTRACT: LESSONS LEARNED: The addition of the heat shock protein 27 (Hsp27)-targeting antisense oligonucleotide, apatorsen, to a standard first-line chemotherapy regimen did not result in improved survival in unselected patients with metastatic pancreatic cancer.Findings from this trial hint at the possible prognostic and predictive value of serum Hsp27 that may warrant further investigation. BACKGROUND: This randomized, double-blinded, phase II trial evaluated the efficacy of gemcitabine/nab-paclitaxel plus either apatorsen, an antisense oligonucleotide targeting heat shock protein 27 (Hsp27) mRNA, or placebo in patients with metastatic pancreatic cancer. METHODS: Patients were randomized 1:1 to Arm A (gemcitabine/nab-paclitaxel plus apatorsen) or Arm B (gemcitabine/nab-paclitaxel plus placebo). Treatment was administered in 28-day cycles, with restaging every 2 cycles, until progression or intolerable toxicity. Serum Hsp27 levels were analyzed at baseline and on treatment. The primary endpoint was overall survival (OS). RESULTS: One hundred thirty-two patients were enrolled, 66 per arm. Cytopenias and fatigue were the most frequent grade 3/4 treatment-related adverse events for both arms. Median progression-free survival (PFS) and OS were 2.7 and 5.3 months, respectively, for arm A, and 3.8 and 6.9 months, respectively, for arm B. Objective response rate was 18% for both arms. Patients with high serum level of Hsp27 represented a poor-prognosis subgroup who may have derived modest benefit from addition of apatorsen. CONCLUSION: Addition of apatorsen to chemotherapy does not improve outcomes in unselected patients with metastatic pancreatic cancer in the first-line setting, although a trend toward prolonged PFS and OS in patients with high baseline serum Hsp27 suggests this therapy may warrant further evaluation in this subgroup.

13 Clinical Trial A phase 1 clinical trial of ASG-5ME, a novel drug-antibody conjugate targeting SLC44A4, in patients with advanced pancreatic and gastric cancers. 2016

Coveler, Andrew L / Ko, Andrew H / Catenacci, Daniel V T / Von Hoff, Daniel / Becerra, Carlos / Whiting, Nancy C / Yang, Jing / Wolpin, Brian. ·Seattle Cancer Care Alliance, University of Washington, 825 Eastlake Ave E, Seattle, WA, 98109, USA. acoveler@u.washington.edu. · Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA, USA. · University of Chicago, Chicago, IL, USA. · TGen Clinical Research Service at Scottsdale Healthcare, Scottsdale, AZ, USA. · Texas Oncology, Baylor Sammons Cancer Center, Dallas, TX, USA. · Seattle Genetics, Inc., Bothell, WA, USA. · Dana-Farber Cancer Institute, Boston, MA, USA. ·Invest New Drugs · Pubmed #26994014.

ABSTRACT: Purpose ASG-5ME is an antibody-drug conjugate (ADC) targeting SLC44A4, a novel cell surface target expressed on most pancreatic and gastric cancers. This first-in-human study of ASG-5ME evaluated safety, pharmacokinetics, and preliminary activity of ASG-5ME in advanced pancreatic and gastric cancer patients. Experimental Design This phase 1, dose-escalation, multicenter study determined the maximum tolerated dose (MTD) and assessed safety and antitumor activity. The dose-escalation portion enrolled metastatic pancreatic adenocarcinoma patients; gastric adenocarcinoma patients were included in the dose-expansion portion. Patients received ASG-5ME intravenously on Days 1, 8, and 15 of 28-day cycles. Results Thirty-five pancreatic cancer patients (median age 63 years; performance status 0 [40 %] or 1 [60 %]) were treated at doses of 0.3 to 1.5 mg/kg (median duration 8.1 weeks). The MTD was exceeded at 1.5 mg/kg (n = 7) with 1 dose-limiting toxicity (DLT) of Grade 4 gastrointestinal hemorrhage. Four patients experienced non-DLT Grade 3 or 4 neutropenia. Fifteen gastric cancer patients (median age 59 years; performance status 0 [33 %] or 1 [67 %]) were treated at the identified MTD of 1.2 mg/kg (median duration 8.7 weeks). Common drug-related adverse events included fatigue (29 %), nausea (23 %), and vomiting (23 %) for pancreatic cancer patients and fatigue (33 %) and decreased appetite (33 %) for gastric cancer patients. Best clinical response was 1 partial response in each cohort. Disease-control rates of 33 % (pancreatic) and 47 % (gastric) were observed at the MTD. All patient biopsies (23 pancreatic, 15 gastric) expressed the SLC44A4 antigen. Conclusions ASG-5ME treatment was generally well tolerated with limited evidence of antitumor activity.

14 Clinical Trial A Phase I Study of FOLFIRINOX Plus IPI-926, a Hedgehog Pathway Inhibitor, for Advanced Pancreatic Adenocarcinoma. 2016

Ko, Andrew H / LoConte, Noelle / Tempero, Margaret A / Walker, Evan J / Kate Kelley, R / Lewis, Stephanie / Chang, Wei-Chou / Kantoff, Emily / Vannier, Michael W / Catenacci, Daniel V / Venook, Alan P / Kindler, Hedy L. ·From the *Division of Hematology/Oncology, University of California San Francisco, San Francisco, CA; †Division of Hematology/Oncology, University of Wisconsin, Madison, WI; ‡Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; and §Department of Radiology and ∥Division of Hematology/Oncology, University of Chicago, Chicago, IL. ·Pancreas · Pubmed #26390428.

ABSTRACT: OBJECTIVES: In mouse models of pancreatic cancer, IPI-926, an oral Hedgehog inhibitor, increases chemotherapy delivery by depleting tumor-associated stroma. This multicenter phase Ib study evaluated IPI-926 in combination with FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, oxaliplatin) in patients with advanced pancreatic cancer. METHODS: Patients were treated with once-daily IPI-926 plus FOLFIRINOX. A 3 + 3 dose escalation design was used, with cohort expansion at the maximum tolerated dose. A subset of patients underwent perfusion computed tomography to assess changes in tumor perfusion. RESULTS: The maximum tolerated dose was identified 1 dose level below standard FOLFIRINOX. Common treatment-related adverse events included liver function test abnormalities, neuropathy, nausea/vomiting, and diarrhea. Objective response rate was high (67%), and patients receiving IPI-926 maintenance showed further declines in CA19-9 levels even after FOLFIRINOX discontinuation. Treatment did not result in consistent increases in tumor perfusion. The study closed early when a separate phase II trial of IPI-926 plus gemcitabine indicated detrimental effects of this combination. CONCLUSIONS: This is the first study to demonstrate the feasibility of using FOLFIRINOX as the chemotherapeutic backbone in a clinical trial design. Although robust antitumor activity and acceptable safety were observed with the addition of IPI-926 to this regimen, future development of Hedgehog inhibitors in pancreatic cancer seems unlikely.

15 Clinical Trial A Multicenter, Open-Label Phase II Clinical Trial of Combined MEK plus EGFR Inhibition for Chemotherapy-Refractory Advanced Pancreatic Adenocarcinoma. 2016

Ko, Andrew H / Bekaii-Saab, Tanios / Van Ziffle, Jessica / Mirzoeva, Olga M / Joseph, Nancy M / Talasaz, AmirAli / Kuhn, Peter / Tempero, Margaret A / Collisson, Eric A / Kelley, R Kate / Venook, Alan P / Dito, Elizabeth / Ong, Anna / Ziyeh, Sharvina / Courtin, Ryan / Linetskaya, Regina / Tahiri, Sanaa / Korn, W Michael. ·Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California. andrewko@medicine.ucsf.edu. · Ohio State University Comprehensive Cancer Center, Columbus, Ohio. · Department of Pathology, University of California San Francisco, San Francisco, California. · Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California. · Guardant Health, Inc., Redwood City, California. · University of Southern California, Los Angeles, California. ·Clin Cancer Res · Pubmed #26251290.

ABSTRACT: PURPOSE: On the basis of preclinical evidence of synergistic activity between MEK and EGFR inhibitors in pancreatic ductal adenocarcinoma (PDAC), we evaluated the safety and efficacy of selumetinib, a MEK1/2 inhibitor, plus erlotinib in patients with previously treated advanced PDAC. EXPERIMENTAL DESIGN: In this single-arm phase II trial, eligible patients received the combination of erlotinib 100 mg plus selumetinib 100 mg daily in 3-week cycles. Study assessments included measurement of clinical outcomes, with a primary endpoint of overall survival, and exploration of potential molecular predictors of treatment benefit. RESULTS: Forty-six patients were enrolled and received a median of two cycles (range, 1-7). Although no objective responses were observed, 19 patients (41%) showed evidence of stable disease for ≥6 weeks, and 13 of 34 patients (38%) had a CA19-9 decline ≥50%. Median progression-free survival was 1.9 months [95% confidence interval (CI), 1.4-3.3 months], with a median overall survival of 7.3 months (95% CI, 5.2-8.0 months). Common adverse events included rash, diarrhea, and nausea/vomiting. Patients with tumors exhibiting an epithelial phenotype (demonstrated by a high level of E-cadherin expression) were more likely to be sensitive to study treatment. Tumor-derived DNA was detectable in plasma from the majority of patients using next-generation digital DNA sequencing, and its relative abundance correlated with tumor burden. CONCLUSIONS: A therapeutic strategy of dual targeted inhibition of the MEK and EGFR pathways shows modest antitumor activity in pancreatic cancer. Specific molecular subtypes may derive greatest benefit from this combination. Further exploration, both with more potent MEK inhibitors and in molecularly enriched patient subsets, is warranted.

16 Clinical Trial Treatment-related Hypertension as a Pharmacodynamic Biomarker for the Efficacy of Bevacizumab in Advanced Pancreas Cancer: A Pooled Analysis of 4 Prospective Trials of Gemcitabine-based Therapy With Bevacizumab. 2016

Pant, Shubham / Martin, Ludmila K / Geyer, Susan / Wei, Lai / Van Loon, Katherine / Sommovilla, Nili / Zalupski, Mark / Iyer, Renuka / Fogelman, David / Ko, Andrew H / Bekaii-Saab, Tanios. ·*Department of Oncology, Oklahoma University, Oklahoma City, OK †Department of Internal Medicine, The Ohio State University, Columbus, OH ‡Department of Internal Medicine, University of California, San Francisco, CA §Mount Sinai School of Medicine, One Gustave Levy Place, New York ¶Roswell Park Cancer Institute, Buffalo, NY ∥1500 E Medical Center Dr, University of Michigan, Ann Arbor, MI #MD Anderson Cancer Center, Houston, TX. ·Am J Clin Oncol · Pubmed #25068471.

ABSTRACT: PURPOSE: Phase III studies of bevacizumab in advanced pancreas cancer (APCA) demonstrated no improvement in outcome. No validated biomarkers for bevacizumab efficacy exist. We evaluated bevacizumab-related hypertension (B-HTN) as a biomarker in APCA patients in a pooled analysis from 4 prospective clinical trials of gemcitabine-based therapy combined with bevacizumab. MATERIALS AND METHODS: Data were collected from individual databases from 4 prospective, single-arm phase II trials. Patients were grouped according to B-HTN or no hypertension (HTN), and patients with HTN were further grouped according to highest Common Terminology Criteria for Adverse Events grade of HTN: grade 1-2 or grade 3-4. Clinical outcomes of overall survival, time to progression, overall response rate (ORR), and disease control rate (ORR+SD>16 wk) were compared. RESULTS: A total of 163 patients with stage IV APCA and Eastern Cooperative Oncology Group 0-1 were included. Median age was 59 years (range, 33 to 85 y). Thirty-four patients had B-HTN, and 129 patients had no HTN. Prognostic factors were balanced between groups. Patients with any grade B-HTN had a significantly improved median overall survival (13.1 vs. 8.1 mo, P=0.0006), median time to tumor progression (7.6 vs. 5.5 mo, P=0.0074), ORR (47% vs. 16%, P=0.0001), and disease control rate (85% vs. 59%, P=0.004). There were no differences in outcomes according to HTN grade (1-2 [N=16] vs. 3-4 [N=18]). CONCLUSIONS: APCA patients who develop any grade of B-HTN appear to derive benefit from bevacizumab. Additional investigation is needed to identify subgroups of patients who develop B-HTN and are more likely to benefit from bevacizumab.

17 Clinical Trial Baseline serum albumin is a predictive biomarker for patients with advanced pancreatic cancer treated with bevacizumab: a pooled analysis of 7 prospective trials of gemcitabine-based therapy with or without bevacizumab. 2014

Pant, Shubham / Martin, Ludmila K / Geyer, Susan / Wei, Lai / Van Loon, Katherine / Sommovilla, Nili / Zalupski, Mark / Iyer, Renuka / Fogelman, David / Ko, Andrew H / Bekaii-Saab, Tanios. ·Division of Hematology and Oncology, Department of Medicine, University of Oklahoma, Oklahoma City, Oklahoma. ·Cancer · Pubmed #24633933.

ABSTRACT: BACKGROUND: Phase 3 studies of bevacizumab in patients with advanced pancreatic cancer (APCA) demonstrated no improvement in outcome. To the authors' knowledge, no validated predictive biomarkers for bevacizumab exist, although emerging data suggest that subsets of patients with APCA may benefit from treatment with bevacizumab. The authors evaluated baseline serum albumin (b-alb) as a predictive biomarker in a pooled analysis from 7 prospective clinical trials of gemcitabine-based therapy with or without bevacizumab. METHODS: Data were collected from individual databases from 7 prospective clinical trials. Patients were grouped by exposure to bevacizumab and by b-alb level (≥ 3.4 g/L or < 3.4 g/dL). Overall survival (OS), time to disease progression (TTP), overall response rate, and disease control rate (overall response rate plus stable disease lasting ≥ 16 weeks) were compared between groups. Univariate and multivariable analyses of prognostic factors were performed. RESULTS: A total of 264 patients were included. The median age was 59 years (range, 31 years-85 years) and all patients had stage IV disease per TNM staging. Normal b-alb was associated with significantly improved median OS (10.2 months vs 4.1 months; P = .0001), median TTP (6.2 months vs 3.7 months; P = 0.0488), and disease control rate (71% vs 46%; P = .007) for patients receiving bevacizumab, but not for those treated without bevacizumab. Multivariable analysis revealed a significant influence of normal b-alb on OS (P = .0008) and TTP (P = .033). CONCLUSIONS: Patients with APCA with normal b-alb derive benefit from treatment with bevacizumab. Future prospective investigations of bevacizumab in patients with APCA should consider selecting patients with normal b-alb to maximize potential benefit.

18 Clinical Trial A multinational phase 2 study of nanoliposomal irinotecan sucrosofate (PEP02, MM-398) for patients with gemcitabine-refractory metastatic pancreatic cancer. 2013

Ko, A H / Tempero, M A / Shan, Y-S / Su, W-C / Lin, Y-L / Dito, E / Ong, A / Wang, Y-W / Yeh, C G / Chen, L-T. ·Division of Hematology/Oncology, Comprehensive Cancer Center, University of California, San Francisco, 1600 Divisadero Street, San Francisco, CA 94115, USA. andrewko@medicine.ucsf.edu ·Br J Cancer · Pubmed #23880820.

ABSTRACT: BACKGROUND: PEP02, also known as MM-398, is a novel nanoliposomal irinotecan that has improved pharmacokinetics and tumour bio-distribution of the free drug. This phase 2 study evaluated PEP02 monotherapy as second-line treatment for pancreatic cancer. METHODS: Patients who had metastatic pancreatic adenocarcinoma, Karnofsky performance status ≥70, and had progressed following gemcitabine-based therapy were eligible. Intravenous injection of PEP02 120 mg m(-2) was given every 3 weeks. Simon 2-stage design was used. The primary objective was 3-month survival rate (OS(3-month)). RESULTS: A total of 40 patients were enrolled. The most common severe adverse events included neutropenia, abdominal pain, asthenia, and diarrhoea. Three patients (7.5%) achieved an objective response, with an additional 17 (42.5%) demonstrating stable disease for a minimum of two cycles. Ten (31.3%) of 32 patients with an elevated baseline CA19-9 had a >50% biomarker decline. The study met its primary end point with an OS(3-month) of 75%, with median progression-free survival and overall survival of 2.4 and 5.2 months, respectively. CONCLUSION: PEP02 demonstrates moderate antitumour activity with a manageable side effect profile for metastatic, gemcitabine-refractory pancreatic cancer patients. Given the limited treatment options available to this patient population, a phase 3 trial of PEP02 (MM-398), referred to as NAPOLI-1, is currently underway.

19 Clinical Trial A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. 2012

Ko, Andrew H / Truong, Thach-Giao / Kantoff, Emily / Jones, Kimberly A / Dito, Elizabeth / Ong, Anna / Tempero, Margaret A. ·Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 94115, USA. andrewko@medicine.ucsf.edu ·Cancer Chemother Pharmacol · Pubmed #23053263.

ABSTRACT: BACKGROUND: Substantial antitumor activity has previously been demonstrated with the addition of nab-paclitaxel (Abraxane [Celgene, Summit, NJ]), an albumin-bound formulation of paclitaxel, to gemcitabine in patients with advanced pancreatic cancer. Given preclinical evidence of synergy when a fluoropyrimidine is added to gemcitabine plus a taxane in a sequence-specific schedule, we conducted a phase I study to evaluate the combination of nab-paclitaxel, gemcitabine, and capecitabine administered biweekly in patients with metastatic pancreatic adenocarcinoma. MATERIALS AND METHODS: Patients with previously untreated metastatic pancreatic cancer and an ECOG performance status of 0-1 were eligible to participate. Study design utilized a 3 + 3 dose-escalation schema, with expanded cohort at maximum-tolerated dose (MTD). Treatment was administered in 14-day cycles, with capecitabine given on days 1-7 and both gemcitabine (at fixed-dose rate infusion) and nab-paclitaxel on day 4 of each cycle. Dose-limiting toxicity (DLT) definitions included grade 3-4 hematologic toxicities and grade 2-4 hand-foot syndrome, neuropathy, or diarrhea. RESULTS: Fifteen patients were enrolled across two dose levels. Final MTD was established at nab-paclitaxel 100 mg/m(2), gemcitabine 750 mg/m(2), and capecitabine 750 mg/m(2) twice daily. Patients received a median of four treatment cycles (range 1-16). The most frequent adverse events (any grade) for the entire study cohort included fatigue, rash/hand-foot syndrome, nausea/vomiting, diarrhea, neuropathy, and elevated liver function tests. Ten patients (66.7 %) experienced at least one grade 3-4 adverse event. Grade 3-4 hematologic toxicities were uncommon. Two of 14 evaluable patients (14.3 %) exhibited a partial response, and 6 of 12 patients (50 %) with elevated CA19-9 at baseline had a ≥50 % biomarker decline. CONCLUSION: While well tolerated overall, this regimen demonstrated only modest antitumor activity in patients with metastatic pancreatic cancer. Recognizing the limits of cross-study comparisons and small sample size, these results do not match those reported at MTD in the phase I/II trial of gemcitabine/nab-paclitaxel. The lower doses used in the current study suggest that dose intensity may be a critical aspect to optimize multidrug regimens.

20 Clinical Trial A phase II randomized study of cetuximab and bevacizumab alone or in combination with gemcitabine as first-line therapy for metastatic pancreatic adenocarcinoma. 2012

Ko, Andrew H / Youssoufian, Hagop / Gurtler, Jayne / Dicke, Karel / Kayaleh, Omar / Lenz, Heinz-Josef / Keaton, Mark / Katz, Terry / Ballal, Shaila / Rowinsky, Eric K. ·Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, 1600 Divisadero Street, 4th Floor, Box 1705, San Francisco, CA 94115, USA. andrewko@medicine.ucsf.edu ·Invest New Drugs · Pubmed #21629990.

ABSTRACT: The purpose of this study was to assess the efficacy and safety of bevacizumab plus cetuximab with or without gemcitabine in patients with advanced pancreatic adenocarcinoma. Patients with locally advanced or metastatic pancreatic adenocarcinoma, previously untreated, were randomized to bevacizumab (10 mg/kg q2w) plus cetuximab (400/250 mg/m(2) initial/weekly), either with (Arm A) or without (Arm B) gemcitabine (1000 mg/m(2) weekly × 3 of 4 weeks). Tumor assessments were performed q8w. Primary study endpoint was progression-free survival (PFS). Sixty-one patients were randomized to Arm A (n = 30) or Arm B (n = 31). Median treatment duration was 9 weeks in Arm A and 8 weeks in Arm B (range, 2.0-40.4). Patients in Arm A had median PFS and overall survival values of 3.55 months and 5.41 months, respectively, compared to 1.91 months and 4.17 months in Arm B. The study closed early due to lack of sufficient efficacy in both treatment arms. Although both regimens were well tolerated, patients treated with gemcitabine experienced more grade 3-4 toxicities, including proteinuria and thromboembolic events. The combination of cetuximab and bevacizumab did not result in promising activity with or without gemcitabine, suggesting that a strategy of dual EGFR/VEGF inhibition in pancreatic cancer does not warrant further development. To our knowledge, this is one of the first trials to evaluate a completely noncytotoxic regimen in the first-line treatment of advanced pancreatic cancer. (ClinicalTrials.gov number, NCT00326911).

21 Clinical Trial Optimizing the administration of fixed-dose rate gemcitabine plus capecitabine using an alternating-week schedule: a dose finding and early efficacy study in advanced pancreatic and biliary carcinomas. 2012

Ko, Andrew H / Espinoza, Anne M / Jones, Kimberly A / Venook, Alan P / Bergsland, Emily K / Kelley, Robin K / Dito, Elizabeth / Ong, Anna / Hanover, Cherry S / Coakley, Fergus V / Tempero, Margaret A. ·Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. andrewko@medicine.ucsf.edu ·Am J Clin Oncol · Pubmed #21552099.

ABSTRACT: OBJECTIVES: This multisite study sought to optimize the dosing, schedule, and administration of fixed-dose rate (FDR) gemcitabine plus capecitabine for advanced pancreatic and biliary tract cancers using an alternating-week dose schedule of both agents. METHODS: Patients with previously untreated advanced pancreatic and biliary tract cancers with Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. For the dose-finding portion, a standard 3+3 dose-escalation schema was used, with the gemcitabine dose kept at 1000 mg/m(2) administered by FDR (10 mg/m(2)/min) on day 1 of each 14-day cycle, and capecitabine given on days 1 to 7 at doses ranging from 800 to 1500 mg/m(2) twice daily. Primary study objective was determination of maximum tolerated dose (MTD). The cohort at MTD was expanded for further efficacy assessment. RESULTS: A total of 45 patients (median age 61 y; 93% pancreatic/7% biliary; 84% with metastatic disease) were enrolled. Median number of cycles received was 11.5. The MTD using this dose schedule was FDR gemcitabine 1000 mg/m(2) plus capecitabine 1000 mg/m(2) bid, due to a high incidence of late hand-foot syndrome observed at the next higher dose level. Most common nonhematologic adverse events related to treatment included nausea/vomiting (overall rate, 64%; all grade 1/2) and hand-foot syndrome (overall rate, 60%; grade 3, 22%). The incidence of grade 3/4 hematologic adverse events was 24%. Six of 41 evaluable patients (14.6%) had a partial response; 18 of 31 patients (58%) with elevated baseline CA 19-9 level had ≥50% biomarker decline during treatment. Estimated median time to tumor progression and overall survival were 5.5 and 9.8 months, respectively (5.5 and 10.1 mo in the metastatic pancreatic cancer cohort). CONCLUSIONS: This dosing schedule of FDR gemcitabine plus capecitabine is active in patients with advanced pancreatobiliary cancers. Given its favorable toxicity profile and convenience, this regimen represents an appropriate front-line option for this patient population and may serve as the foundation on which new investigational agents are added in future trial design.

22 Clinical Trial A phase II study of bevacizumab plus erlotinib for gemcitabine-refractory metastatic pancreatic cancer. 2010

Ko, Andrew H / Venook, Alan P / Bergsland, Emily K / Kelley, R Kate / Korn, W Michael / Dito, Elizabeth / Schillinger, Brian / Scott, Janet / Hwang, Jimmy / Tempero, Margaret A. ·University of California at San Francisco Helen Diller Family Comprehensive Cancer Center, 1600 Divisadero Street, 4th Floor, Box 1705, San Francisco, CA 94115, USA. andrewko@medicine.ucsf.edu ·Cancer Chemother Pharmacol · Pubmed #20130876.

ABSTRACT: PURPOSE: No standard of care exists for patients with metastatic pancreatic cancer following progression on first-line chemotherapy. Based on potential for additive or synergistic activity by concurrent inhibition of VEGF and EGFR, we conducted a phase II study evaluating the combination of bevacizumab plus erlotinib in this patient population. METHODS: Patients with metastatic pancreatic adenocarcinoma, ECOG performance status 0-1, and previous exposure to 1-3 systemic therapies (at least one gemcitabine-based) were eligible. Treatment consisted of bevacizumab 15 mg/kg every 21 days plus erlotinib 150 mg daily. RESULTS: Thirty-six patients were enrolled, including eight who had previously received VEGF-targeted therapy and nine prior erlotinib. Median number of treatment cycles was 2 (range, 1-7). Common toxicities included rash (72%), diarrhea (25%), venous thromboembolic events (15%), and hypertension (11%). One patient demonstrated partial response and seven others stable disease for >2 cycles. CA19-9 decline ≥25% was observed in 4/26 patients with baseline levels >2x ULN. Estimated median time to progression was 40 days (95% CI, 35-41 days) and median survival 102 days (95% CI, 74-117 days), with a 6-month survival rate of 22%. Baseline concentration of circulating endothelial cells (CD45(-)/CD34(+)/CD31(+)) was inversely associated with overall survival. CONCLUSIONS: The combination of bevacizumab and erlotinib is safe but relatively ineffective in patients with gemcitabine-refractory metastatic pancreatic cancer. Future studies should focus on refining subsets of patients in this challenging population likely to benefit from treatment beyond first-line.

23 Article Randomized, double-blind, placebo-controlled phase II study of istiratumab (MM-141) plus nab-paclitaxel and gemcitabine versus nab-paclitaxel and gemcitabine in front-line metastatic pancreatic cancer (CARRIE). 2020

Kundranda, M / Gracian, A C / Zafar, S F / Meiri, E / Bendell, J / Algül, H / Rivera, F / Ahn, E R / Watkins, D / Pelzer, U / Charu, V / Zalutskaya, A / Kuesters, G / Pipas, J M / Santillana, S / Askoxylakis, V / Ko, A H. ·Medical Oncology, Banner MD Anderson Cancer Center, Gilbert, USA. · Medical Oncology, Centro Integral Oncologico Clara Campal, Madrid, Spain; Departamento de Ciencias Médicas Clínicas, Universidad CEU San Pablo, Madrid, Spain. · Hematology and Oncology, Florida Cancer Specialists, Fort Myers, USA. · Medical Oncology, Comprehensive Care and Research Center, Atlanta, USA. · GI Oncology, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, USA. · TUM School of Medicine, Klinikum rechts der Isar, Medizinische Klinik II, Technical University of Munich, Munich, Germany. · Medical Oncology, Hospital Universitario Marques de Valdecilla, Santander, Spain. · Medical Oncology, Cancer Treatment Centers of America Chicago, Zion, USA. · Department of Medicine, Royal Marsden Hospital, Sutton, UK. · Charité - Universitätsmedizin Berlin, Germany. · Hematology/Oncology, Pacific Cancer Medical Center, Anaheim, USA. · Clinical Development, Merrimack Pharmaceuticals, Inc., Cambridge, USA. · Hematology/Oncology, University of California San Francisco Cancer Center, San Francisco, USA. Electronic address: andrew.ko@ucsf.edu. ·Ann Oncol · Pubmed #31912800.

ABSTRACT: BACKGROUND: Preclinical data suggest that dual blockade of the insulin-like growth factor-1 receptor (IGF-1R) and HER3 pathways has superior activity to IGF-1R blockade alone in pancreatic ductal adenocarcinoma (PDAC). We tested whether istiratumab, an IGF-1R- and ErbB3-bispecific antibody, can enhance the efficacy of standard of care (SOC) chemotherapy in patients with metastatic PDAC selected for high IGF-1 serum levels. PATIENTS AND METHODS: CARRIE was an international, randomized, double-blind, placebo-controlled phase II study for patients with previously untreated metastatic PDAC. In part 1, 10 patients were evaluated for pharmacokinetics and safety. In part 2, patients with high free serum IGF-1 levels were randomized 1 : 1 to receive either istiratumab [2.8 g intravenously (i.v.) every 2 weeks] or placebo combined with gemcitabine/nab-paclitaxel at approved dose schedule. The co-primary endpoints were progression-free survival (PFS) in patients with high IGF-1 levels and PFS in patients with both high serum IGF-1 levels and heregulin (HRG)+ tumors. Key secondary endpoints were overall survival (OS), objective response rate (ORR) by RECIST v.1.1, and adverse events (AEs) rate. RESULTS: A total of 317 patients were screened, with 88 patients randomized in part 2 (experimental arm n = 43; control n = 45). In the high IGF-1 cohort, median PFS was 3.6 and 7.3 months in the experimental versus control arms, respectively [hazard ratio (HR) = 1.88, P = 0.027]. In the high IGF-1/HRG+ subgroup (n = 44), median PFS was 4.1 and 7.3 months, respectively (HR = 1.39, P = 0.42). Median OS and ORR for the overall population were similar between two arms. No significant difference in serious or grade ≥3 AEs was observed, although low-grade AEs leading to early discontinuation were higher in the experimental (39.5%) versus control arm (24.4%). CONCLUSIONS: Istiratumab failed to improve the efficacy of SOC chemotherapy in this patient setting. High serum IGF-1 levels did not appear to be an adverse prognostic factor when compared with non-biomarker-selected historic controls. CLINICAL TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov: NCT02399137; EUDRA CT: 2014-004572-34.

24 Article CA 19-9 Response: A Surrogate to Predict Survival in Patients With Metastatic Pancreatic Adenocarcinoma. 2019

Diaz, Celso L / Cinar, Pelin / Hwang, Jimmy / Ko, Andrew H / Tempero, Margaret A. ·School of Medicine, University of California. · Department of Medicine, Division of Hematology/Oncology, University of California. · UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA. ·Am J Clin Oncol · Pubmed #31634155.

ABSTRACT: OBJECTIVE: The objective of this study was to determine the features of carbohydrate antigen (CA) 19-9 decline that correlates best with survival benefit in patients with metastatic pancreatic cancer. METHODS: This is a retrospective study of 225 patients with metastatic pancreatic cancer receiving first-line therapy. Analysis was performed by the Kaplan-Meier method and Cox-proportional hazards ratios. CA 19-9 decline was grouped into quartiles within different CA 19-9 baseline groups. Time to nadir and CA 19-9 decline at month-2 (M2) of therapy were evaluated for patients with a baseline level ≥1000 U/mL. RESULTS: No significant trend in survival was observed across baseline CA 19-9 levels. The greatest survival benefit was seen with a ≥75% decline to nadir. Among those with a ≥75% decline and baseline ≥1000 U/mL, 43 of 57 patients had a >50% decline at M2 of therapy and additional survival benefit was observed with a slower decline to nadir. Small sample sizes limited analysis of other baseline groups. CA 19-9 decline at M2 was not predictive. CONCLUSIONS: In patients with a CA 19-9 ≥1000 U/mL, serial CA 19-9 levels may be considered as a surrogate for serial imaging to evaluate treatment response, with a ≥75% decline indicating the greatest survival benefit. Survival was improved further in the setting of a slower decline to nadir with the highest benefit seen in patients with a nadir occurring at 4 months or longer.

25 Article Alternate Week Gemcitabine and Capecitabine: An Effective Treatment for Patients With Pancreatic Adenocarcinoma. 2019

Johns, Claire / Diaz, Celso L / Hwang, Jimmy / Kerridge, William D / Ko, Andrew H / Tempero, Margaret A. ·Department of Medicine, Northwestern University, Chicago, IL. · Helen Diller Comprehensive Cancer Center, UCSF Medical Center, San Francisco. · Department of Radiology, The Permanente Medical Group, Kaiser Permanente, Santa Rosa. · Division of Hematology and Oncology, Department of Medicine, UCSF Medical Center, San Francisco, CA. ·Pancreas · Pubmed #31268983.

ABSTRACT: OBJECTIVE: Determine whether a regimen of fixed dose rate gemcitabine plus capecitabine is effective and tolerable for advanced pancreatic adenocarcinoma. METHODS: We performed a retrospective analysis of 62 patients with locally advanced or metastatic pancreatic adenocarcinoma treated at the University of California San Francisco between 2008 and 2016. Treatment was an alternate week schedule of fixed dose rate 1000 mg/m gemcitabine and capecitabine 1000 mg/m (58 patients), 1200 mg/m (12 patients), or 650 mg/m (1 patient) for intended 12 cycles. We evaluated overall survival (OS), progression-free survival (PFS), radiologic response, and adverse events necessitating treatment modification. RESULTS: For metastatic patients, median OS was 10.3 months (95% confidence interval [CI], 6.7-12.1 months), and PFS was 5.6 months (95% CI, 2.6-7.7 months). In locally advanced patients, OS was 12.0 months (95% CI, 4.9-17.1 months), and PFS was 5.4 months (95% CI, 2.5-9.4 months). Radiologic response for metastatic disease (42 patients) was 19% objective response, 45% stable disease, and 36% progressive disease. Treatment required modification for 22 patients due to adverse events, most frequently hand-foot syndrome (18 patients). CONCLUSIONS: Alternate week schedule of fixed dose rate gemcitabine and capecitabine was active and tolerable for advanced pancreatic adenocarcinoma. Overall survival and PFS were comparable to first-line treatments. Importantly, adverse effects appear less severe than first-line treatments.