Contemporary Management of Borderline Resectable and Locally Advanced Unresectable Pancreatic Cancer (original) (raw)
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Current Systemic Treatment Options for Metastatic and Unresectable Pancreatic Cancer
Pancreatic Cancer [Working Title]
Metastatic and local advanced unresectable pancreatic cancers are lethal conditions that always carry a poor prognosis with rare exceptions. Currently, the mainstay of therapy is cytotoxic chemotherapy plus best supportive care. First-line therapy for patients with a good performance status includes FOLFIRINOX or gemcitabine plus nab-paclitaxel regimens. Patients carrying a deleterious germline BRCA mutation can be treated with maintenance olaparib after FOLFIRINOX. Patients with a poor performance status, but still fit enough for chemotherapy, may be treated with single agent gemcitabine. Second-line therapy will depend on previous therapy and current performance status. Options for patients treated with gemcitabine-based regimens are 5-fluorouracil plus leucovorin plus either nanoliposomal irinotecan, irinotecan or oxaliplatin. Patients that were treated with first line FOLFIRINOX may benefit from a gemcitabine-based chemotherapy, but evidence from randomized trials is lacking. Other options like immunotherapy and targeted therapies yield benefit only in very selected cases, and it is still an area of research.
Locally advanced pancreatic cancer — new therapeutic challenges
Nowotwory. Journal of Oncology, 2016
The overall survival rate of patients with pancreatic ductal adenocarcinoma remains extremely poor, and the only potentially curative treatment is radical surgery. There are three subgroups among the patients: primary resectable, metastatic and locally advanced pancreatic cancer. The term of locally ad advanced pancreatic cancer includes borderline resectable pancreatic cancer (BRPC) and unresectable pancreatic cancer (URPC). As in the case of BRPC, the strategy of induction treatment may convert the inoperable tumour into a resectable one. As in the case of URPC, the optimal standard of treatment is unknown. Recent advances in systemic treatment such as FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, oxaliplatin) and gemcitabine plus nab-paclitaxel as well as the optimisation of local treatment such as stereotactic radiotherapy (SBRT-stereotactic body radiation therapy) should be incorporated into future trials dedicated for BRPC and URPC.
Anticancer research, 2018
Combination nab-paclitaxel/gemcitabine (AG) is superior to gemcitabine in patients with metastatic pancreatic cancer (PC). There are limited data for AG in borderline resectable (BR) or locally advanced pancreatic cancer (LAPC). Herein, we report our experience with neoadjuvant AG for BR/LAPC in patients ineligible for FOLFIRINOX. This retrospective series, included patients with BR/LAPC who received AG as neoadjuvant therapy for 3-4 months followed by radiation, then re-evaluation for surgery. Between 10/2013-2/2018, 32 patients (22 BR, 10 LAPC) were treated with this approach. Median age was 70 years. Nine patients were converted to resectability by imaging; six had R0 resections (19%), five (16%) achieved a partial response and 24 (75%) had stable disease. In this small series, the R0 resection rate and response rate were 19% and 16% respectively. These data suggest that neoadjuvant AG may be an alternate option for patients ineligible for FOLFIRINOX.
Advancements in the Management of Pancreatic Cancer
Management of pancreatic cancer remains the most challenging work in oncology. Though pancreatic cancer represents only 2-3% of all cancers, it is the most fatal one accounting for the 6% of all cancer death. It remains the 4 th cause of death by cancer since 1970s in the U.S.. Gemcitabine remains the only standard of care for this disease. More and more combination therapies containing gemcitabine have been tested or undergoing investigation. The interest in treating pancreatic cancer is apparently global. Over 75 abstracts were presented in the 2009 ASCO Gastrointestinal Cancers Symposium at San Francisco in the field of pancreatic cancer. In this highlights article, authors summarize the critical studies in the management of pancreatic cancer. A large retrospective study evaluated the role of post-operative adjuvant radiation (Abstract #181) and correlated the receipt of radiation with survival benefit. Borderline resectable pancreatic cancer remains an area that requires multi-disciplinary approach. Neo-adjuvant therapy very likely plays a role to downstage to a resectable state in these subgroup patients (Abstracts #197 and #248). In advanced or metastatic setting, studies aiming at the gemcitabine-based triplet or doublet combinations are still the mainstream. FFCD 0301 trial (Abstract #180), the only large phase III trial presented in the first-line setting, failed to demonstrate any survival advantage of either 5-FU and leucovorin plus cisplatin followed by gemcitabine or vice versa. Biologic agents containing regimens were also presented. Of note, gemcitabine and oxaliplatin plus bevacizumab achieved a high response rate of 39% (Abstract #182) while gemcitabine with dual monoclonal antibody regimen was disappointing (Abstract #183). The clear benefit of all other combinations over gemcitabine alone remains questionable given most studies are small. Newer agents, especially S-1 (Abstracts #213 and #251), are very promising, and further studies are warranted. In a nut shell, pancreatic cancer continues to pose an enormous challenge to clinicians and cancer scientists. With a more affluent world the global incidence of pancreatic cancer is rising. This meeting again emphasizes us that it is urgent to make big inroads into what still remains the most lethal of the common.
ESMO Open, 2020
Introduction Pancreatic cancer (PC), even in the absence of metastatic disease, has a dismal prognosis. One-third of them are borderline resectable (BRPC) or locally advanced unresectable PC (LAUPC) at diagnosis. There are limited prospective data supporting the best approach on these tumours. Neoadjuvant chemotherapy (ChT) is being increasingly used in this setting. Methods This is a retrospective series of consecutive patients staged as BRPC or LAUPC after discussion in the multidisciplinary board (MDB) at an academic centre. All received neoadjuvant ChT, followed by chemoradiation (ChRT) in some cases, and those achieving enough downstaging had a curative-intent surgery. Descriptive data about patient's characteristics, neoadjuvant treatments, toxicities, curative resections, postoperative complications, pathology reports and adjuvant treatment were collected. Overall survival (OS) and progression-free survival was calculated with Kaplan-Meier method and log-rank test. Results Between August 2011 and July 2019, 49 patients fulfilled the inclusion criteria, and all of them received neoadjuvant ChT. Fluorouracil+folinic acid, irinotecan and oxaliplatin was the most frequently used scheme (77%). The most prevalent grade 3 or 4 toxicities were neutropenia (26.5%), neurotoxicity (12.2%), diarrhoea (8.2%) and nausea (8.2%). 18 patients (36.7%) received ChRT thereafter. In total, 22 patients (44,9%) became potentially resectable and 19 of them had an R0 or R1 pancreatic resection. One was found to be unresectable at surgery and two refused surgery. A vascular resection was required in 7 (35%). No postoperative deaths were observed. Postoperative ChT was given to 12 (66.7%) of resected patients. Median OS of the whole cohort was 24,9 months (95% CI 14.1 to 35.7), with 30.6 months for resected and 13.1 months for non-resected patients, respectively (p<0.001). Conclusion A neoadjuvant approach in BRPC and LAUPC was well tolerated and allowed a curative resection in 38.8% of them with a potential improvement on OS. How might this impact on clinical practice? ► This work confirms that fluorouracil+folinic acid, irinotecan and oxaliplatin or gemcitabine plus nabpaclitaxel, widely used on metastatic pancreatic cancer, are tolerable with manageable toxicities. They induce tumour downstaging and a complete tumour resection in some cases, potentially leading to an improvement in overall survival.
Cancers
Therapy with gemcitabine and nab-paclitaxel (GNP) is the most commonly used palliative chemotherapy, but its advantage in the neoadjuvant setting remains unclear. Accordingly, our aim is to evaluate the impact of first-line neoadjuvant therapy with GNP in patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC). A systematic search for published studies until August 2020 was performed. The primary endpoint included resection and R0 resection rates in the intention-to-treat population. Secondary endpoints were response rate, survival and toxicity. Among 21 studies, 950 patients who received neoadjuvant GNP were evaluated. Treatment with GNP resulted in surgical resection and R0 resection rates as follows: 49% (95% CI 30–68%) and 36% (95% CI 17–58%) for BRPC and 16% (95% CI 7–26%) and 11% (95% CI 5–19%) for LAPC, respectively. The objective response rates and the median overall survival (mOS) ranged from 0 to 67% and 12 to 30 months, respectively. Neutr...
Borderline resectable pancreatic cancer: On the edge of survival
Cancer control: journal of the Moffitt Cancer Center
Patients with borderline resectable pancreatic cancer are at high risk of having positive surgical margins due to involvement of the tumor with adjacent vasculature. This article reviews the management of this subset of pancreatic cancer patients.
Phase II study of cisplatin, gemcitabine and 5-fluorouracil in advanced pancreatic cancer
Annals of Oncology, 2004
The aim of this study was to determine the activity of the combination of cisplatin, gemcitabine and 5-fluorouracil (5-FU) as therapy for metastatic or locally advanced inoperable pancreatic adenocarcinoma. Patients and methods: Patients with histologically proven advanced or metastatic pancreatic adenocarcinoma received first-line chemotherapy comprising cisplatin (20 mg/m 2 on days 1, 8, 15, 22, 29 and 36), gemcitabine (1000 mg/m 2 on days 1, 8, 29 and 36) and 5-FU (200 mg/m 2 as continuous infusion on days 1-42) every 56 days. Results: A total of 34 patients were studied. Eighty courses were administered (median two courses per patient). Among 32 patients evaluable for response, two patients had a complete response and four a partial response for an overall response rate of 19% (95% confidence interval 7% to 36%). Thirteen patients had stable disease (40%) and 13 progressed. Median progression-free survival was 4.7 months, median survival 9.0 months and 26% of patients achieved 1-year survival. Ten of 25 patients (40%) with pain at presentation had a sustained reduction of analgesic consumption. The principal grade 3/4 toxicities were neutropenia, thrombocytopenia, anaemia and mucositis, occurring in 24%, 21%, 9% and 3% of patients. Conclusion: This schedule seems well tolerated and active in pancreatic cancer and worthwhile of further evaluation.
Cancers, 2021
Background: Gemcitabine/nab-paclitaxel (GN) and FOLFIRINOX (FFX) are two standard first-line therapies for metastatic pancreatic cancer (PC) but have rarely been compared, especially in patients with locally advanced PC (LAPC). Methods: This is a retrospective European multicenter study including patients with LAPC treated with either GN or FFX as the first-line therapy between 2010 and 2019. Coprimary objectives were progression-free survival (PFS) and overall survival (OS), both estimated using the Kaplan–Meier method. Results: A total of 147 patients (GN: n = 60; FFX: n = 87) were included. Tumor resection rates were similar between the two groups (16.7% vs. 16.1%; p = 1), with similar R0 resection rates (88.9%). Median PFS rates were not statistically different: 9 months (95% CI: 8–13.5) vs. 12.1 months (95% CI: 10.1–14.6; p = 0.8), respectively. Median OS rates were 15.7 months (95% CI: 12.6–20.2) and 16.7 months (95% CI: 14.8–20.4; p = 0.7), respectively. Abdominal pain at the...