Locally advanced pancreatic adenocarcinoma: update and progress.
ABSTRACT Pancreatic cancer, the 4th leading cause of cancer death in the U.S., remains a challenging disease for the oncology community. Less than 20% of all cases are potentially cured by surgical resection, while the large majority of cases are deemed either unresectable or metastatic upon diagnosis. Advances in treating locally advanced pancreatic cancer have been few and modest. In this year's American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, three abstracts (#252, #254, #313) were presented with novel approaches towards treating locally advanced pancreatic cancer. Surgery for recurrent disease, a promising new chemoradiation regimen, and the application of an exciting multi-agent regimen (FOLFIRINOX: oxaliplatin, irinotecan, leucovorin, 5-fluorouracil) in a non-clinical trial setting, highlight the novel approaches focused on the management of this difficult disease.
- SourceAvailable from: Muhammad Wasif Saif[Show abstract] [Hide abstract]
ABSTRACT: Therapeutic options for locally advanced pancreatic cancer (LAPC) include concurrent chemoradiation, induction chemotherapy followed by chemoradiation or systemic therapy alone. The original Gastro-Intestinal Study Group and Eastern Cooperative Oncology Group studies defined fluorouracil (5-FU) with concurrent radiation therapy followed by maintenance 5-FU until progression, as the standard therapy for this subset of patients. Although this combined therapy has been demonstrated to increase local control and median survival from 8 to 12 months, almost all patients succumb to the disease secondary to either local or distant recurrence. Our earlier studies provided a strong rationale for the use of capecitabine in combination with concurrent radiation followed by maintenance capecitabine therapy. To report our clinical experience, we retrospectively evaluated our patients who were treated with maintenance capecitabine. We reviewed the medical records of patients with LAPC who received treatment with capecitabine and radiation, followed by a 4-week rest, then capecitabine alone 1,000 mg twice daily (ECOG performance status 2 or age >70 years) or 1,500 mg twice daily for 14 days every 3 weeks until progressive disease. We treated 43 patients between September 2004 and September 2012. The population consisted of 16 females and 25 males, with a median age of 64 years (range, 38-80 years). Patients received maintenance capecitabine for median duration of 9 months (range, 3-18 months). The median overall survival (OS) for these patients was 17 months, with two patients still living and receiving therapy. The 6-month survival rate was 91% (39/43), 1-year survival rate was 72% (31/43) and 2-year OS rate was 26% (11/43). Grade 3 or 4 toxicity was observed rarely: Hand-foot syndrome (HFS) in two patients, diarrhea in one patient and peripheral neuropathy in one patient, and there was no mortality directly related to treatment. Capecitabine maintenance therapy following chemoradiation in LAPC offers an effective, tolerable and convenient alternative to 5-FU. To the best of our knowledge, this is the largest study of its kind which has determined the safety and efficacy of capecitabine maintenance therapy for patients with LAPC.Oncology letters 09/2014; 8(3):1302-1306. · 0.24 Impact Factor
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ABSTRACT: Patients with advanced pancreatic adenocarcinoma have a poor prognosis, and to date, no treatment method has had a significant impact on the disease. In general, the mean overall survival time of such patients receiving conventional chemotherapy and radiotherapy is <6 months. In the present case report, a patient with advanced pancreatic adenocarcinoma experienced a longer progression-free survival (PFS) of >19 months, following cytokine-induced killer (CIK) cell therapy. To the best of our knowledge, no study has previously described such a beneficial effect on patients only receiving CIK cell immunotherapy. Based on these findings, CIK cell therapy may be a potential treatment regimen that is capable of leading to an improved prognosis in certain patients with advanced pancreatic adenocarcinoma.Oncology letters 04/2013; 5(4):1427-1429. · 0.24 Impact Factor
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ABSTRACT: Curcumin (CUR), a naturally occurring polyphenol derived from the root of Curcuma longa, has demonstrated potent anti-cancer and cancer prevention activity in a variety of cancers. However, the clinical translation of curcumin has been significantly hampered due to its extensive degradation, suboptimal pharmacokinetics and poor bioavailability. To address these clinically relevant issues, we have developed a novel curcumin loaded magnetic nanoparticle (MNP-CUR) formulation. Herein, we have evaluated the in vitro and in vivo therapeutic efficacy of this novel MNP-CUR formulation in pancreatic cancer. Human pancreatic cancer cells (HPAF-II and Panc-1) exhibited efficient internalization of the MNP-CUR formulation in a dose dependent manner. As a result, the MNP-CUR formulation effectively inhibited growth of HPAF-II and Panc-1 cells in cell proliferation and colony formation assays. The MNP-CUR formulation suppressed pancreatic tumor growth in an HPAF-II xenograft mice model and improved mice survival by delaying tumor growth. The growth inhibitory effect of MNP-CUR formulation was correlated with the suppression of PCNA, Bcl-xL, Mcl-1, MUC1, Collagen I and enhanced membrane β-catenin expression. MNP-CUR formulation did not show any sign of hemotoxicity and was stable after incubation with human serum proteins. Additionally, the MNP-CUR formulation improved serum bioavailability of curcumin in mice up to 2.5 fold as compared to free curcumin. Biodistribution studies demonstrate that a significant amount of MNP-CUR formulation was able to reach the pancreatic xenograft tumor(s) which suggests its clinical translational potential. In conclusion, this study suggests that our novel MNP-CUR formulation can be valuable for the treatment of pancreatic cancer.Molecular Cancer Therapeutics 05/2013; · 5.60 Impact Factor