Chronic Use of Long-Acting Somatostatin Analogues (SSAs) and Exocrine Pancreatic Insufficiency (EPI) in Patients with Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs): An Under-recognized Adverse Effect.

Background: Somatostatin Analogues (SSAs) are used to treat Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and acromegaly. Side effects of SAAs usually include biliary disorders, gastrointestinal disorders, injection-site pain and hyperglycemia. Exocrine Pancreatic Insufficiency (EPI) is often misdiagnosed as disease progression or failure to SAAs or diagnosed after a delay in patients receiving SAAs. We present our experience with EPI developing in patients following use of SAAs. Methods: We reviewed chart and pharmacy records of 110 GEP-NETs patients who received SSAs. Data was collected including demographics, pathology, stage, dose/duration of long and short-acting SA, use of antidiarrheal, pancreatic enzyme replacement (PER), proton pump inhibitors (PPI) or H2 blockers). Laboratory data include chromogranin-A (CgA), urine 5-HIAA and quantitative fecal fat test (QFFT) or fecal elastase test (FE). EPI was defined by a FE below normal level OR by a reduction of ≥ 21.2% or steatorrhea on QFFT. Patients who were identified to develop EPI were treated with pancreatic exocrine replacement therapy (PERT). Results: Among, 110 GEP-NETs patients, 104 received LA Octreotide and 6 Somatuline Depot Injection. Of these, 23 received short-acting SSA for worsening diarrhea, 96 had intensification of antidiarrheal and 1 got telotristat ethyl. QFFT confirmed EPI in 19, 11 based on clinical symptoms, and 16 had sample error or refusal to collect specimen. CTCAE 4.0 grades of EPI were: grade 2(69%), grade 3(22%) and grade 4(9%). Median time to development of EPI was 12 months (95%CI 3 - 23). Except 1, all patients received PERT either with concomitant PPI (13) or later if no improvement with PERT (6) and 2 on H2 blockers. 37% of the patients had improvement in EPI within 4-8 weeks. Deficiency of vitamins and trace elements was found in 11 of 19 patients, who received supplementation. Conclusions: Our experience constitutes the first and the largest study addressing EPI as a rare but serious complication of chronic use of SAAs. Although SAAs are used to treat diarrhea, paradoxically they can worsen diarrhea secondary to EPI. Early recognition and diagnosis of this under-diagnosed and under-reported side effect of SAAs, such as EPI, can improve not only diarrhea and weight loss in these patients but also can reduce cost of using short-acting SAAs and antidiarrheal.

New concepts in the treatment strategy of neuroendocrine tumors: the role of biotherapy.

Neuroendocrine tumors (NETs) comprise a wide range of neoplasms with diverse biological behaviors, often secreting excessive amounts of endocrine-active substances causing hormone syndromes. They are classified according to the location of the primary site and the level of histological differentiation, which has prognostic as well as therapeutic implications. Biotherapy had traditionally a significant role in the treatment of these tumors, when not amenable to surgery or local treatments. Control of carcinoid syndrome with somatostatin analogs (SSAs) significantly contributed to the improvement of the quality of life. Also, interferon has long been administered, but data were based on small studies. In contrast, PROMID and CLARINET randomized phase III trials provided the first strong evidence of significant improvement in progression-free survival in patients with gastroenteropancreatic (GEP)-NETs with octreotide and lanreotide, respectively, validating somatostatin receptors as important targets. Clinical trials testing the role of these SSAs in other primaries, e.g., lung carcinoids, as well as the efficacy of newer analogs are underway.

Benefit of uridine triacetate (Vistogard) in rescuing severe 5-fluorouracil toxicity in patients with dihydropyrimidine dehydrogenase (DPYD) deficiency.

BACKGROUND: 5-Fluorouracil (5-FU), an analog of uracil, is one of the most commonly used chemotherapeutic agents and like other agents has a narrow therapeutic index limited by toxicity. Compared to previous attempts, uridine triacetate (Vistogard) has shown to increase the potential efficacy of 5-FU by allowing administering a higher dose and decreasing the toxicity. Recently, Vistogard received orphan drug designation from the FDA as an antidote in the treatment of 5-FU poisoning and from the European Medicines Agency as a treatment for 5-FU overdose. However, no data have been published to date in humans who were rescued by this agent following severe toxicity associated with 5-FU due to dihydropyrimidine dehydrogenase (DPYD) deficiency, the enzyme which is responsible for the elimination of approximately 80 % of the administered dose of 5-FU. PATIENTS AND METHODS: We identified two patients with advanced pancreatic cancer who were referred to us for testing of DPYD status following severe toxicity associated with 5-FU administered at a dose of 1400 mg/m(2) weekly bolus high-dose 5-FU followed by oral uridine triacetate as a part of a clinical trail. One patient developed grade 3 thrombocytopenia and grade 3 skin rash that resolved with discontinuation of 5-FU and supportive care, while second patient developed grade 4 thrombocytopenia, grade 3 coagulopathy and grade 3 neurological toxicity with a fatal outcome. DPYD status was evaluated as we have previously published. RESULTS: The first patient was found to have an abnormally low DPYD activity of 0.087-nmol/min/mg protein by radioisotopic assay (reference normal range 0.182-0.688 nmol/min/mg protein). Because of pancytopenia, DPYD enzyme activity could not be assessed in patient 2; genotypic analysis of DPYD during autopsy revealed the presence of the heterozygous mutation, IVS14+1 G>A, DPYD*2A, now recognized as the most common cause of DPYD deficiency. CONCLUSION: These two patients present the first two cases of DPYD deficiency that had either delay in severe toxicity or recovered from severe toxicity as they received oral Vistogard as a part of the conical trial. Toxicity was delayed in both patients by a mean of 3.5 weeks (range 3-4 weeks), indicating that Vistogard might be able to delay 5-FU toxicity despite higher doses than standard bolus dose of 5-FU used in gastrointestinal malignancies and the appearance of a potentially less toxic adverse effect of 5-FU at an unusual site (cutaneous) in one patient. The role of uridine triacetate with 5-FU in DPYD-deficient patients needs further investigation.

TAS-102 an Emerging Oral Fluoropyrimidine.

Colon cancer is a common type of cancer with high mortality. The standard therapy for colon cancer is 5-FU-based regimen, although the current response rate to 5-FU is only 10-15%. Various approaches have been used to improve the efficacy of 5-FU including inhibition of its degradation enzyme dihydropyrimidine dehydrogenase (DPD) such as S1, UTF, use of 5-FU pro-drug capecitabine to exploit thymidine phosphorylase (TP) and supplementation of reduced folate acid to increase cytotoxicity. TAS-102 is a newly-developed anti-folate drug containing the 5-FU analogue trifluridine (TFD) and tipiracil hydrochloride (TPI). TPI is an inhibitor of TFD degradation enzyme thymidine phosphorylase and thus increases the bioavailability of TFD. In the present review, we summarize recent progress with regard to TAS-102, including pre-clinical tests and clinical trials. We further propose several approaches to further improve the efficacy of TAS-102 including combination with targeted therapy and immune therapy.

Safety and efficacy of radiofrequency ablation with aflibercept and FOLFIRI in a patient with metastatic colorectal cancer.

BACKGROUND: A vast majority of patients with metastatic colorectal cancer (mCRC) are not candidates for surgical resection. Radiofrequency ablation (RFA) is a safe and effective technique for treatment of isolated liver metastasis. After radiofrequency ablation, residual tumor can have aggressive growth, part of which is driven by the up-regulation of vascular endothelial growth factor (VEGF). Angiogenesis inhibitor bevacuzimab has been used in the management of mCRC with RFA. We present a patient with recurrent colorectal cancer and four hepatic metastases who was treated with RFA combined with aflibercept, another VEGF inhibitor and systemic chemotherapy. We believe that this is the first report of using aflibercept with RFA. CASE REPORT: A 35-year-old female with stage IV rectal cancer with metastasis to a lymph node and multiple hepatic metastases was treated with chemo-radiation, surgical resection of the tumor and surgical resection of two segments of the liver. She underwent RFA of the hepatic lesions that could not be resected. She received adjuvant chemotherapy consisting of 5-fluorouracil (5-FU) and oxaliplatin for a total of 6 months. However, a positron emission tomography (PET) scan showed progression of disease with new and growing lymph nodes. She was treated with 6 cycles of capecitabine monotherapy. A follow-up PET scan showed four new liver lesions. She has RFA of her four liver lesions and was started on a combination of aflibercept and FOLFIRI. She received 10 cycles and a repeat magnetic resonance imaging (MRI) and PET scan showed stable disease. DISCUSSION: This is the first reported case of a patient managed with RFA with aflibercept, an anti-VEGF agent, and FOLFIRI. This case showed both efficacy, as well as safety for the combined modalities in the management of mCRC.

Role of neoadjuvant therapy in management of pancreatic cancer.

Surgery remains the only curative treatment for pancreatic cancer; however, majority of patients present with advanced unresectable disease upon diagnosis. Treatment of nonmetastatic, locally advanced pancreatic cancer (LAPC) continues to require multidisciplinary bimodality or trimodality approach. Neoadjuvant therapies have been investigated for LAPC given its established role in other solid cancers such as breast cancer, gastric cancer, and rectal cancer. This strategy is now moving forward to management of potentially resectable disease as well. This meeting highlight focuses on recent updates on neoadjuvant therapy for both borderline resectable disease and potentially resectable disease, Abstracts #4120, #e15189, #e15226 and #TPS4158 will be discussed.

Advanced stage pancreatic cancer: novel therapeutic options.

Despite advances in our understanding of the molecular and genetic basis of pancreatic cancer, it continues to be a therapeutic challenge. Gemcitabine approved by FDA in 1997, offers modest improvement of tumor-related symptoms and marginal advantage of survival. Many chemotherapeutic agents have been compared against or combined with gemcitabine in randomized Phase III trials and no drug was shown to be superior to single-agent gemcitabine except FOLFIRINOX and nab-paclitaxel plus gemcitabine. On the other hand, efforts to integrate targeted agents such as BAY 12-9566, SCH 66336, bevacizumab, cetuximab, axitinib and sorafenib have been quite dismal despite extensive pre-clinical and clinical research over the last decade in the field of novel agents. To date, erlotinib remains the only biological agent that has demonstrated a small, but significant, added benefit to single agent gemcitabine. However, numerous new agents, including monoclonal antibodies and tyrosine kinase inhibitors, are currently being tested in an attempt to achieve better response, while maintaining a safe toxicity profile. In this article, the author discusses the management of advanced pancreatic and the current role of novel agents in this setting.

First-in-human phase II trial of the botanical formulation PHY906 with capecitabine as second-line therapy in patients with advanced pancreatic cancer.

BACKGROUND: Preclinical studies showed a Chinese botanical formula, PHY906, has synergistic anti-tumor activity with capecitabine. Our phase I study determined maximal tolerated dose of capecitabine 1,500 mg/m(2) BID day 1-7 and PHY906 800 mg BID day 1-4 every 2 weeks. We conducted this phase II study to explore the efficacy of capecitabine and PHY906 in patients with advanced pancreatic cancer who were previously treated with gemcitabine-based regimens. METHODS: Patients with pancreatic cancer and an Eastern Cooperative Oncology Group performance status of 0-2 received PHY906 and capecitabine. Toxicity was assessed per NCI-CTCAE v3.0 and response per response evaluation criteria in solid tumors q 6 weeks. Correlative studies of cytokines, chemokines and growth factors were tested using a cytometric bead array. Quality of life was assessed by utilizing Edmonton symptom assessment system. The primary objective was overall survival. RESULTS: The study enrolled 25 patients. Median progression-free survival (mPFS) was 10.1 weeks (range 0.4-54.1) and median overall survival (mOS) was 21.6 weeks (range 0.4-84.1). Eighteen patients received at least 2 cycles, and achieved mPFS of 12.3 weeks and mOS of 28 weeks. Six-month survival rate was 44 % (11/25). Unsupervised clustering of patients grouped those with shortened survival together by their cytokine profile showed that only IL-6 had a significant difference (p < .001) between short- and long-term survivors. CONCLUSIONS: Capecitabine plus PHY906 provides a safe and feasible salvage therapy after gemcitabine failure for APC. Role of IL-6 in tumor progression and tumor cachexia needs to be investigated with respect to its relation to pathophysiology of pancreatic cancer and development of anti-IL-6 therapeutics.

Topical henna ameliorated capecitabine-induced hand-foot syndrome.

BACKGROUND: Hand-foot syndrome (HFS) is the most frequently reported side effect of oral capecitabine therapy. In addition to treatment interruption and dose reduction, supportive treatments can help alleviate symptoms. Although its efficacy has not been proven in clinical studies, certain authors report on the use of prophylactic or therapeutic pyridoxine supplementation for the prevention of minimization to be useful in preventing worsening of HFS but are no substitute for dose modifications. CASE REPORT: We report a case of an interesting observation in a patient with pancreatic cancer receiving capecitabine whose HFS was improved with the use of "henna". DISCUSSION: Henna has been used for histories as a medicine, preservative, and cosmetic. Our case underlines the basis to further evaluate the anti-inflammatory, antipyretic, and analgesic effects of henna. We encourage other investigators to publish any similar cases or any other herbal or non-drug therapies. HFS is a common side effect of many drugs, including capecitabine, sorafinib and regorafenib. HFS is bothersome for patients even in low grades and impacts quality of life of patients. HFS cannot be prevented and currently the treatments aimed at controlling syndrome are not very effective. Exploring other potential treatment or management options such as henna is of high value.

Pharmacogenomics in pancreatic adenocarcinoma: new data and their clinical implications.

Despite advances and investments in translation research, clinical trials and health service in general, there is no significant impact on the survival of most patients diagnosed with advanced pancreatic adenocarcinoma. It is broadly recognized though that there is a small minority of patients who really benefit from particular treatments for reason usually not well understood. Light to this fact is gradually shed by developments in the field of pharmacogenomics, which plays pivotal role in what we call individualized medicine. In that perspective, it is of most importance to present the significant developments in pharmacogenomics announced in the recent 2013 American Society of Clinical Oncology Annual Meeting. First, the predictive role of hENT1, which codes for a gemcitabine transporter into cells, was highlighted and might help us decide whether we benefit from gemcitabine or 5-fluorouracil in the adjuvant setting (Abstract #4006). Second, authors presented the negative predictive role of SPARC stroma and cytoplasmic expression in patients treated with adjuvant gemcitabine (within the CONCO-001 study) as they reported poor outcome of those having high expression, not seen in patients on observation (Abstract #4016). Finally, a study which might be a basis for future strategies and as great food for scientific thought suggested that selection of cytotoxic treatment based on gene expression profiling is feasible in clinical practice and may help improve treatment efficacy as well as predict for drug resistance (Abstract #4017). Of course, there is a long way to go before implementation of these genomic findings, with the exception of hENT1 which seems to be close for clinical use.

Radiotherapy in the management of pancreatic neuroendocrine tumors (PNET): experience at three institutions.

AIM: Advanced pancreatic neuroendocrine tumor (PNET) presents a therapeutic challenge as many are unresectable and relatively resistant to systemic therapy with a high malignant potential. We share our experience using concurrent capecitabine or infusional 5-fluorouracil with radiation for patients with resected and locally advanced PNET. PATIENTS AND METHODS: Six patients (two females, four males) with PNET were treated with capecitabine or infusional 5-FU and concurrent radiation. RESULTS: The median age was 52 years (range: 38 to 63 years), with ECOG Performance Status (PS) 0-1, grade 0-1 weight loss, and grade 0-1 pain. One patient underwent resection with negative margins, two with positive margins, and three had unresectable locally advanced disease. All six patients demonstrated partial radiographic response and sustained local control. The treatment was tolerable with only grade 2 hand-foot syndrome and grade 1 mucositis observed. CONCLUSION: Prospective studies to further investigate the role of chemoradiation in this setting are warranted.

Advancements in the management of pancreatic cancer: 2013.

Pancreatic cancer still remains a significant, unresolved therapeutic challenge and is the most lethal type of gastrointestinal cancer with a 5-year survival rate of 5%. Adjuvant chemotherapy remains to be gemcitabine alone, though fluorouracil offers the same survival and role of radiation remains controversial. Nevertheless, only a few patients survive for at least 5 years after R0 resection and adjuvant therapy. 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. There are different treatment approaches to locally advanced pancreatic cancer management, including single or multi-agent chemotherapy, chemotherapy followed by chemoradiation, or immediate concurrent chemoradiation. Most patients need palliative treatment. Once pancreatic cancer becomes metastatic, it is uniformly fatal with an overall survival of generally 6 months from time of diagnosis. Gemcitabine has been the standard since 1997. FOLFIRINOX (5-fluorouracil, oxaliplatin, irinotecan, leucovorin) has already shown superiority over gemcitabine in both progression-free survival and overall survival, but this regimen is suitable only for selected patients in ECOG performance status 0-1. FOLFIRINOX has already trickled down to the clinic in various modifications and in different patient groups, both locally advanced and metastatic. Many targeted agents, including bevacizumab, cetuximab showed negative results, except mild benefit with addition of erlotinib with gemcitabine, which was not considered clinically significant. There is no consensus regarding treatment in the second-line setting. It will be true to say that there was a real medical breakthrough with regards to improving the prognosis of pancreatic cancer as of 2013 with the results of MPACT study. In this study, patients who received nab-paclitaxel plus gemcitabine lived a median of 8.5 months, compared with 6.7 months for those who received gemcitabine alone. At the end of one year, 35% of those getting nab-paclitaxel were alive, compared with 22% of those getting only gemcitabine. After two years, the figures were 9% for those getting nab-paclitaxel and 4% for those who received gemcitabine.

Second-line therapy in pancreatic cancer.

At the time of diagnosis most of patients present with advanced or metastatic pancreatic cancer, thereby precluding surgical resection. While the standard of care in the first line setting is established, there are limited data to support a standard second-line chemotherapy regimen. The authors summarize two interesting studies (Abstract #263 and Abstract #287) presented at the 2013 ASCO Gastrointestinal Cancers Symposium. These studies concern two phase II trials about second-line chemotherapy in pancreatic cancer. The first one evaluated the role of fluoropyrimidine as monotherapy versus fluoropyrimidine in combination with irinotecan (Abstract #263) and the second one compared the fluoropyrimidine treatment with the continuation of gemcitabine as monotherapy (Abstract #287).

New tools and novel approaches in treating locally advanced pancreatic adenocarcinoma.

Pancreatic adenocarcinoma is one of the most aggressive malignant tumors and represents the fourth leading cause of cancer-related death. The median survival of locally advanced pancreatic carcinoma is ten to thirteen months. In this year's American Society of Clinical Oncology (ASCO) Annual Meeting, several studies were presented with novel approaches towards treating locally advanced pancreatic cancer. Wild et al. (Abstract #4055) explored a novel tool of selective delivery of TNF-alpha intratumoral injection. This approach limited the systemic toxicity, and suggested survival benefit in only the subgroup of patients with locally advanced pancreatic adenocarcinoma with stage T1-T3. Two studies were presented which were designed to assess the use of two novel agents, targeting signaling pathways, in addition to gemcitabine. Van Laethem et al. (Abstract #4050) are testing the MEK inhibitor, BAY 86-9766 in combination with gemcitabine. However, treatment related toxicity is still of concern. In the other study, Evans et al. (Abstract #TPS4134) are testing the combination of dasatinib and gemcitabine. This is a placebo-controlled, randomized, double blind phase II study. However, results are not available. Stereotactic body radiotherapy (SBRT) is an emerging technology with the comparative efficacy of single fraction radiotherapy (as is used in radiosurgery) vs. fractionated SBRT still unknown. Herman et al. (Abstract #4045) examined the role of fractionated SBRT in locally advanced pancreatic cancer. The phase II results showed a median overall survival of 15.9 months, suggesting that SBRT may be an emerging tool in the multi-modality treatment of locally advanced pancreatic cancer.

Pancreatic neuroendocrine tumors: entering a new era.

Neuroendocrine tumors (NETs) describe a heterogeneous group of tumors with a wide range of morphologic, functional, and behavioral characteristics. These tumors are generally slow growing and behave in an indolent fashion. However, they have the potential to spread, primarily to the liver and when they do, they can be life threatening and difficult to treat with current modalities. A subset of NETs, the pancreatic neuroendocrine tumors (pNET) represent a small percentage of all pancreatic tumors (1.3%) but their incidence is rising. Prior to 2011, the only approved agent for unresectable pNETs was streptozocin (often used in combination with doxorubicin) but the efficacy of this drug was questionable. In 2011, the landscape of treatment for pNET was changed with the approval of the first new agents in 20 years, sunitinib and everolimus, that demonstrated improvement in time to progression in patients with progressive pNET. Sunitinib is a multikinase inhibitor and everolimus is an inhibitor of the mammalian target of rapamycin (mTOR) pathway. These drugs were approved by the Food and Drug Administration (FDA) on the basis of separate large randomized placebo-controlled trials. Data from these two trials and an additional phase III trial looking at everolimus in other neuroendocrine tumors has generated intense interest in this challenging disease. At the 2012 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, several researchers presented updated data regarding the risk stratification, treatment, and outcome for patients with pNET in the new era of targeted therapy. Choti et al. (Abstract #187) reviewed demographic data from a large set of patients who presented to National Comprehensive Cancer Network (NCCN) sites with neuroendocrine tumors. Casciano et al. (Abstract #226) and Signorovitch et al. (Abstract #237) presented post-approval analysis of the relative role of everolimus and sunitinib in the treatment of pNET. Alistar et al. (Abstract #166) explored predictive biomarkers in pNET, and Yao et al. (Abstract #157) conducted multivariate analysis of patients treated with everolimus in the phase III, RADIANT-2 trial which included the identification of relevant biomarkers. Hobday et al. (Abstract #260) and Bergsland et al. (Abstract #285) reported phase II data from two clinical trials looking at novel targeted combinations for the treatment of pNET. Finally the role of treatment for poorly differentiated NETs (including pNETs) remains ill-defined and Yamaguchi et al. (Abstract #274) presented a report reviewing the experience at 23 centers in Japan in treating this population. The authors review and summarize these abstracts in this article.

Triphendiol (NV-196), development of a novel therapy for pancreatic cancer.

Despite incremental progress in the treatment of pancreatic adenocarcinoma, the prognosis of patients remains poor. Here, we report the preclinical studies in pancreatic cancer cells that demonstrate the efficacy of triphendiol (NV-196, a synthetic isoflavene) both as a monotherapy and as a gemcitabine sensitizer. The in-vitro effects of triphendiol on the pancreatic cancer cell lines HPAC and MIAPaCa-2 were determined using cell proliferation, flow cytometry, and western blot analysis. The antiproliferative activity of triphendiol was also investigated in two xenograft models of pancreatic cancer (HPAC and MIAPaCa-2). As a monotherapy, triphendiol-inhibited cell proliferation-induced p53-independent G2/M cell cycle arrest and activation of the intrinsic (mitochondrial) apoptosis pathway. Triphendiol-induced apoptosis was caspase independent and death receptor independent, whereas cell necrosis was caspase mediated. Using combination index analysis, we have shown that pretreatment of pancreatic cancer cells with triphendiol enhanced the cytotoxic effect of gemcitabine, the standard of care used to treat advanced pancreatic cancer. In xenograft models of pancreatic cancer, the rate of tumor proliferation on mice coadministered with triphendiol and gemcitabine was significantly reduced when compared with the corresponding tumor proliferation rates from the respective monotherapy-control and vehicle-control groups. Triphendiol was recently granted Investigational New Drug status by the US Food and Drug Administration. These data justify the commencement of clinical studies investigating the utility of combining triphendiol and gemcitabine in patients with early-stage and late-stage pancreatic cancer.

First-line treatment for advanced pancreatic cancer. Highlights from the "2011 ASCO Gastrointestinal Cancers Symposium". San Francisco, CA, USA. January 20-22, 2011.

Pancreatic adenocarcinoma remains a treatment-refractory cancer. Although pancreatic adenocarcinoma is only the 10th most common cause of new cancer in the United States, it is the fourth most common cause of cancer-related death. Most cases are not suitable for resection and a majority is metastatic at presentation. Gemcitabine, with or without erlotinib, has been the standard chemotherapy in this setting but the benefit is only modest. Because gemcitabine has been considered a standard treatment for advanced pancreatic cancer for the past decade, several randomized trials have tested the combination of gemcitabine plus a second agent, including platinum based agents, topoisomerase inhibitors, taxanes, bevacizumab and cetuximab, as biologically "targeted" agents. At large this approach has not been successful and novel strategies are clearly needed. In this article, the authors summarizes the data from the 2011 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, including: Abstract #175 (review of survival data in a large cohort); Abstract #286 (rapid change in prescriber patterns after the suggestion of benefit of a new regimen, FOLFIRINOX); Abstracts #238, #277, #304, and #315 (phase II trials looking at combinations that utilized EGFR blockade); Abstracts #221, #266, and #284 (phase I/II trials including VEGF blockade, anticoagulation, and traditional Chinese medicines).

Adjuvant therapy of pancreatic cancer: beyond gemcitabine. Highlights from the "2011 ASCO Gastrointestinal Cancers Symposium". San Francisco, CA, USA. January 20-22, 2011.

There is no consensus on what constitutes "standard" adjuvant therapy for pancreatic cancer. This controversy derives from several studies, each fraught with its own limitations. Standards of care also vary somewhat on the geography as chemo-radiotherapy followed by chemotherapy or vice versa is considered the optimal therapy in North America (GITSG, RTOG) while chemotherapy alone is the current standard in Europe (ESPAC-1, CONKO, ESPAC-3). The high rate of locoregional failure following surgical resection for adenocarcinoma of the pancreas has made it clear that some form of adjuvant therapy should be considered in these patients. A phase II study was presented at the 2011 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium to assess the effect of the addition of algenpantucel-L immunotherapy to standard adjuvant therapy on survival in patients with resected pancreas cancer (Abstract #236). The author reviews the abstract in the context of our previous knowledge.