FOLFIRINOX for locally advanced and metastatic pancreatic cancer: single institution retrospective review of efficacy and toxicity
Section of Medical Oncology, Department of Medicine, Yale Cancer Center, Yale School of Medicine, 333 Cedar Street, PO Box 208032, New Haven, CT, 06520-8032, USA. Medical Oncology
(Impact Factor: 2.63).
03/2013; 30(1):361. DOI: 10.1007/s12032-012-0361-2
Although FOLFIRINOX significantly increases survival in metastatic pancreatic cancer (MPC) compared to gemcitabine (Conroy et al. N Engl J Med 364:1817-1825, 2011), toxicities have tempered enthusiasm for its use in full doses. To assess the impact of dose attenuations on toxicity and efficacy, we reviewed our institution's experience with FOLFIRINOX in locally advanced pancreatic cancer (LAPC) and MPC. We performed a retrospective review of dose, toxicity, and efficacy of FOLFIRINOX in all patients with LAPC and MPC treated between June 2010 and July 2011 at Yale. Toxicities in all patients and response rate (RR) and survival in previously untreated MPC were compared to data reported by Conroy. Overall survival (OS) and progression-free survival were estimated by Kaplan-Meier method. Thirty-five patients were treated (16 LAPC; 19 MPC). Twenty-nine patients received dose attenuations with the first cycle. Median relative doses of irinotecan and bolus fluorouracil were less than those reported by Conroy (64 vs. 81 % and 66 vs. 82 %, respectively). RR was 50 % in LAPC and 47 % in MPC, and the latter did not differ significantly from the RR reported by Conroy (p = 0.19). OS at 6 and 12 months in MPC was comparable to OS reported by Conroy. Grade 3/4 toxicities were less than reported by Conroy, including fatigue (p = 0.009) and neutropenia (p < 0.0001). Nine patients experienced transient dysarthria during irinotecan administration. Our findings validate the efficacy and tolerability of FOLFIRINOX in LAPC and MPC and suggest that dose attenuations of irinotecan and bolus fluorouracil improve tolerability without compromising efficacy.
Available from: PubMed Central
- "Authors reported significantly less grade 3–4 toxicity but similar activity . Additionally, in a small retrospective analysis of 35 patients treated at the Yale Cancer Center, 29 (85 %) who received dose-attenuated FOLFIRINOX showed no significant reduction in response rate . These results are reassuring and have enhanced the acceptability of this regimen among general oncologists who frequently adjust drug doses based on the individual patient's performance status. "
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ABSTRACT: Over the last couple of years, we have witnessed the availability of a wide variety of different therapeutic agents and the identification of effective combinations of existing ones that have transformed the way we approach and treat pancreatic cancer. Proof of this are the recent validations that combinations of conventional chemotherapy drugs, the FOLFIRINOX regimen and gemcitabine plus nab-paclitaxel, significantly improves clinical outcomes in patients with metastatic disease. However, deeper and more sophisticated understanding of the biology of this cancer as well as the ability to develop better and perhaps more precise drugs predict that the landscape may be changing even more.
In this review, we will summarize the most recent treatment advances including FOLFIRINOX, gemcitabine plus nab-paclitaxel and discuss novel approaches such as immune-mediated therapies, drugs that disrupt the tumor-stromal compartment, PARP inhibitors for BRCA pathway-deficient pancreatic cancer and new generations of conventional chemotherapeutics, which are in early phases of clinical development and have shown promising early results. We will also discuss some examples of drugs that failed, despite very good preliminary data, in order to appraise the lessons learned from these negative clinical trials. Lastly, we will comment on ongoing adjuvant and neoadjuvant trials.
We hope that at least some of these will result in positive trials and add to our armamentarium for treating this challenging malignancy.
Journal of Gastrointestinal Cancer 12/2013; 45(2). DOI:10.1007/s12029-013-9561-z · 0.38 Impact Factor
Available from: annonc.oxfordjournals.org
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ABSTRACT: Neoadjuvant therapy is increasingly becoming a valid treatment option for patients with locally advanced pancreatic cancer
(LAPC). In borderline resectable disease, neoadjuvant therapy is employed to improve the probability of margin-clear resections.
In non-metastatic, non-resectable pancreatic cancer, treatment primarily aims to induce disease control, but may achieve conversion
to surgical resectability in some patients. Several treatment modalities including chemotherapy, chemoradiotherapy (CRT) or
the sequential use of both have been investigated in numerous, mostly small and non-randomized studies. Nevertheless, there
is a consistent finding that neoadjuvant therapy can induce resectability in up to 30%–40% of LAPC patients. Once resection
has been achieved, overall survival appears to be comparable to that observed for primarily resectable patients. Thus, patient
selection evolves as an important aspect of neoadjuvant therapy; retrospective analyses identified induction chemotherapy
as an appropriate tool to define LAPC patients who may benefit most from subsequent treatment with CRT. The clinical importance
of induction chemotherapy may further increase once highly active protocols such as the FOLFIRINOX or the gemcitabine plus
nab-paclitaxel regimen are introduced into novel multimodality treatment concepts.
Annals of Oncology 07/2013; 24(10). DOI:10.1093/annonc/mdt239 · 7.04 Impact Factor
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ABSTRACT: This review intends to describe recent studies on pancreatic tumor-associated stroma and potential opportunities and limitations to its targeting.
One of the defining features of pancreatic cancer is extensive desmoplasia, or an inflammatory, fibrotic reaction. Carcinoma cells live in this complex microenvironment which is comprised of extracellular matrix (ECM), diffusible growth factors, cytokines and a variety of nonepithelial cell types including endothelial cells, immune cells, fibroblasts, myofibroblasts and stellate cells. In addition to the heterogeneity noted in the nonneoplastic cells within the tumor microenvironment, it has also been recognized that neoplastic cancer cells themselves are heterogeneous, and include a subpopulation of stem-cell like cells within tumors termed cancer stem cells. Due to the failure of current therapeutics to improve outcomes in patients with pancreatic cancer, new therapeutic avenues targeting different components of the tumor microenvironment are being investigated. In this review article, we will focus on recent studies regarding the function of the tumor stroma in pancreatic cancer and therapeutic treatments that are being advanced to target the stroma as a critical part of tumor management.
Recent studies have shed new light on the contribution of the pancreatic cancer fibroinflammatory stroma to pancreatic cancer biology. Additional studies are needed to better define its full contribution to tumor behavior and how to best understand the optimal ways to develop therapies that counteract its pro-neoplastic properties.
Current opinion in gastroenterology 07/2013; 29(5). DOI:10.1097/MOG.0b013e328363affe · 4.29 Impact Factor
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