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In 2010, the FOLFIRINOX regimen (bolus and infusional 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) emerged as a new option in patients with metastatic pancreatic cancer and a good performance status. However, at that time, some doubts were raised regarding safety issues. Similarly, no data on FOLFIRINOX were published in patients with unresectable/locally advanced or borderline resectable pancreatic cancer. This article presents the available experience with FOLFIRINOX outside clinical trials in metastatic and locally advanced pancreatic cancer patients. The safety of the regimen in patients with biliary stents and in previously treated patients is also described. FOLFIRINOX usage in clinical practice, including modification of the regimen (omission of bolus 5-fluorouracil; FOLFOXIRI regimen), is also presented. These data suggest that a phase III randomized study is warranted to further explore the role of FOLFIRINOX in locally advanced pancreatic cancer.

Colorectal cancer is a common malignancy and often presents with synchronous or metachronous distant spread. For patients with hepatic metastases, resection is the principal curative option. Liberalization of the indications for hepatic resection has introduced a number of challenges related to the size, distribution, and number of metastases as well as the condition of the future liver remnant. Advances in systemic therapy have solidified its role as both an important adjunct to surgery and also for many patients as a mechanism to facilitate resection. In patients whose disease is marginally resectable as a consequence of the distribution of hepatic lesions that precludes complete resection or out of concern for the future liver remnant, a number of strategies have been advocated, including prehepatectomy systemic therapy, staged surgical approaches, ablative technologies, and preoperative portal vein embolization. It is the purpose of this review to discuss ways in which to optimize the treatment of patients with potentially resectable disease, specifically those who are judged to have “borderline” resectable situations.

Rectal adenocarcinoma is an important cause of cancer-related deaths worldwide, and key anatomic differences between the rectum and the colon have significant implications for management of rectal cancer, especially in the curative setting. For stage II and III rectal cancers, combined chemoradiotherapy offers the lowest rates of local and distant relapse, and is delivered neoadjuvantly to improve tolerability and optimize surgical outcomes, particularly when sphincter-sparing surgery is an endpoint. We review both pivotal trial data that has shaped the current standard of care, fluoropyrimidine-based chemoradiotherapy, while also presenting results from more recent studies, which aim to outperform this standard. Strategies combining 5FU radiotherapy with oxaliplatin, VEGF inhibition, EGFR inhibition, other targeted agents, and/or use of induction chemotherapy hold promise but thus far have failed to improve outcomes in randomized trials. Results of studies such as the ongoing PROSPECT trial may help further define our current therapeutic algorithm for stage II and III rectal cancer.

The diagnosis of stage IV colorectal cancer was once associated with a uniformly grim prognosis. Over the last 20 years, advances in chemotherapeutics, surgical technique, and surgical adjuncts have dramatically broadened treatment options and improved outcomes. Among current treatment options, surgery remains the key component of any multidisciplinary approach with surgical data demonstrating the longest survivorship. This review will summarize current and developing surgical advances in the treatment of metastatic colorectal cancer. Specifically, we will discuss how surgical interventions fit within the greater context of a multi-modality approach, as well as, the specific, recent innovations in the surgical management of hepatic and extrahepatic metastases.

Both the addition of neoadjuvant chemoradiation therapy and improvements in surgical techniques have improved local control and overall survival for locally advanced rectal cancer patients over the past few decades. The addition of adjuvant chemotherapy has likely improved outcomes as well, though the contribution has been more difficult to quantify. At present, the majority of resected locally advanced rectal cancer patients receive adjuvant chemotherapy, though there is great variability in this practice based on both patient and institution characteristics. Recently, questions have been raised regarding which sub-groups of patients benefit most from adjuvant chemotherapy. As pathologic complete response (pCR) is increasingly found to be a reasonable surrogate for long-term favorable outcomes, some have questioned the need for adjuvant therapy in this select group of patients. Multiple retrospective analyses have shown minimal to no benefit for adjuvant chemotherapy in this group. Indeed, the patients most consistently shown to benefit from adjuvant therapy both in terms of disease free survival (DFS) and overall survival (OS) are those who achieve an intermediate pathologic response to neoadjuvant treatment. Tumors that have high expression of thymidylate synthetase have also shown to benefit from adjuvant therapy. More study is needed into clinical and molecular features that predict patient benefit from adjuvant therapy.

Gastric cancer confers a poor prognosis even when diagnosed as localized disease. Multimodality therapy improves the cure rate of patients with localized cancer. However, adjunctive therapeutic approaches differ in different regions of the world. This review focuses on the current standards and unresolved issues based on updated literature on therapy for localized gastric cancer. In the USA, the Intergroup 0116 trial established the use of postoperative chemoradiotherapy as a standard for patients who have surgery first for treatment of gastric cancer. In Europe, the MAGIC trial investigating perioperative chemotherapy demonstrated a survival benefit for gastric cancer patients. Finally, in Asia, the ACTS-GC and CLASSIC trials investigating postoperative chemotherapy established this as the standard of care after primary surgery that included D2 dissection. It is clear, however, that surgery alone is insufficient to achieve the highest possible cure rates.

Although neoadjuvant chemoradiotherapy has been tested for more than two decades and can be safely delivered to patients with non-metastatic pancreatic cancer, no randomised trials have been reported until now. Here we provide an overview of the first randomised trial in patients with potentially resectable cancer and of the latest developments in neoadjuvant therapy for this group of patients. It is necessary to continue to perform clinical trials in this field to accurately identify the effect on survival and quality of life in patients with potentially resectable, borderline resectable and unresectable pancreatic cancer. Aspects of imaging for restaging and clinical prognostic factors are also discussed given they will be useful instruments for future trials.

Anal cancer is an uncommon malignancy. There have been some intriguing developments in the past 3 years, in terms of our understanding of the molecular biology and processes that lead to anal cancer. There have also been some notable successes in prevention, imaging and treatment. Nonsurgical treatment is highly effective. The primary aim of such treatment is to achieve loco-regional control with chemoradiation (CRT), and preserve anal function without a colostomy. Randomised phase III trials presented or published over the past 3 years have explored novel strategies of neoadjuvant chemotherapy, maintenance chemotherapy, radiotherapy dose escalation and replacement of mitomycln C (MMC) with cisplatin in CRT. All have failed to improve on the current standard of care; i.e. MMC/ 5 fluorouracil (5FU) chemoradiation. However, more conformal strategies such as intensity modulated radiotherapy (IMRT) appear feasible to deliver with reduced toxicity, and may offer an opportunity to dose-escalate both to gross tumour and areas of potential nodal spread. Preliminary outcome data suggest no loss of efficacy. We evaluate the relevant recent literature published over the past 2 years, and summarize interesting and important new findings, with the aim of bringing the reader up-to-date on anal cancer.