Radiotherapy has been offered to patients with pancreatic cancer, either in the adjuvant or definitive setting. However, the role of radiotherapy in pancreatic cancer is increasingly doubted, especially after the introduction of gemcitabine to both domains. Although contradictory data exist, combined chemoradiotherapy improves both quantity and quality of life for patients with locally advanced tumors compared with radiotherapy alone or chemotherapy alone. Recently, induction chemotherapy strategy is being evaluated for better selection of patients for optimal benefit from consolidative chemoradiotherapy. Much controversy has been suggested concerning the role of adjuvant radiotherapy, but quality assurance for radiotherapy was not considered in the previously reported studies. Combined chemoradiotherapy in the adjuvant setting is still considered as a viable option. Current phase III randomized on-going studies will provide better answers on the role of radiotherapy in the treatment of pancreatic cancer.
Antimetabolites/therapeutic use ; Antimetabolites, Antineoplastic/therapeutic use ; Combined Modality Therapy ; Deoxycytidine/analogs & derivatives/therapeutic use ; Fluorouracil/therapeutic use ; Humans ; Pancreatic Neoplasms/drug therapy/*radiotherapy

No abstract available.
Antimetabolites, Antineoplastic/*therapeutic use ; Deoxycytidine/*analogs & derivatives/therapeutic use ; Female ; Humans ; Male ; Pancreatic Neoplasms/*drug therapy

Chemotherapy is expected to play an important role in the treatment of pancreatic cancer because most of pancreatic cancers are being discovered at locally advanced or metastatic stages and recurrence rate is high even after the curative resection. Gemcitabine is a key agent for the first-line therapy of advanced pancreatic cancer. It can enhance the quality of life and prolong the survival of patients. Combination of erlotinib or capecitabine with gemcitabine showed a marginal survival benefit over single-agent gemcitabine. If patient's performance state is good, gemcitabine-based platinum combination therapy showed overall survival benefit compared with gemcitabine monothrapy. If the first-line palliative chemotherapy fails, 5-FU, capcitabine, or tegafur with or without combination can be used as the second-line agents. Adjuvant chemotherapy using 5-FU or gemcitabine after curative resection has overall survival benefit. However, neoadjuvant chemotherapy has not been proven to be effective in the treatment of pancreatic cancer.
Antimetabolites/therapeutic use ; Antimetabolites, Antineoplastic/therapeutic use ; Chemotherapy, Adjuvant ; Deoxycytidine/analogs & derivatives/therapeutic use ; Fluorouracil/analogs & derivatives/therapeutic use ; Humans ; Pancreatic Neoplasms/*drug therapy ; Protein Kinase Inhibitors/therapeutic use ; Quinazolines/therapeutic use

No abstract available.
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Antimetabolites/therapeutic use ; Azathioprine/therapeutic use ; Chronic Disease ; Colitis, Ulcerative/diagnosis/*therapy ; Hemoglobins/analysis ; Humans ; Mesalamine/therapeutic use ; Recurrence ; Risk Factors

Aged ; Antimetabolites, Antineoplastic ; therapeutic use ; Azacitidine ; analogs & derivatives ; therapeutic use ; Female ; Humans ; Leukemia, Myelomonocytic, Chronic ; drug therapy

OBJECTIVE5-Fluorouracil (5-FU)-based combination therapies are standard treatments for gastrointestinal cancer, where the modulation of autophagy is becoming increasingly important in offering effective treatment for patients in clinical practice. This review focuses on the role of autophagy in 5-FU-induced tumor suppression and cancer therapy in the digestive system.

DATA SOURCESAll articles published in English from 1996 to date those assess the synergistic effect of autophagy and 5-FU in gastrointestinal cancer therapy were identified through a systematic online search by use of PubMed. The search terms were "autophagy" and "5-FU" and ("colorectal cancer" or "hepatocellular carcinoma" or "pancreatic adenocarcinoma" or "esophageal cancer" or "gallbladder carcinoma" or "gastric cancer").

STUDY SELECTIONCritical reviews on relevant aspects and original articles reporting in vitro and/or in vivo results regarding the efficiency of autophagy and 5-FU in gastrointestinal cancer therapy were reviewed, analyzed, and summarized. The exclusion criteria for the articles were as follows: (1) new materials (e.g., nanomaterial)-induced autophagy; (2) clinical and experimental studies on diagnostic and/or prognostic biomarkers in digestive system cancers; and (3) immunogenic cell death for anticancer chemotherapy.

RESULTSMost cell and animal experiments showed inhibition of autophagy by either pharmacological approaches or via genetic silencing of autophagy regulatory gene, resulting in a promotion of 5-FU-induced cancer cells death. Meanwhile, autophagy also plays a pro-death role and may mediate cell death in certain cancer cells where apoptosis is defective or difficult to induce. The dual role of autophagy complicates the use of autophagy inhibitor or inducer in cancer chemotherapy and generates inconsistency to an extent in clinic trials.

CONCLUSIONAutophagy might be a therapeutic target that sensitizes the 5-FU treatment in gastrointestinal cancer.

Antimetabolites, Antineoplastic ; therapeutic use ; Autophagy ; physiology ; Drug Resistance, Neoplasm ; Fluorouracil ; therapeutic use ; Gastrointestinal Neoplasms ; drug therapy ; pathology ; Humans

Antimetabolites, Antineoplastic ; pharmacology ; therapeutic use ; Drug Resistance, Neoplasm ; Humans ; Methotrexate ; pharmacology ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy

The clinical application of novel chemotherapeutic drugs including oral 5-FU and targeted drugs and preoperatively accurate imaging grading has brought challenges to the indication criteria developed by NCCN and ESMO for neoadjuvant chemoradiotherapy in locally advanced rectal cancer (LARC). Extended hotspots have focused on the effectiveness of using capecitabine instead of fluorouracil infusion, the combination of multiple drugs and the feasibility of using neoadjuvant chemotherapy instead of neoadjuvant chemoradiotherapy for selective patients. Traditionally, the evaluation of the effect of neoadjuvant therapy has been based on the effect on the pathological complete remission (pCR) rate. However, current studies recommend the disease-free survival (DFS) as a more important outcome. Besides, seeking for effective biomarkers as predictive markers for neoadjuvant therapies or as prognostic markers remains a hotspot in the field of neoadjuvant chemoradiotherapy. The "watch and wait" approach refers to taking a close follow-up strategy instead of direct operation for patients achieving clinically complete remission (cCR) after neoadjuvant therapy. However, there is no unified evaluation criteria and time point for the evaluation of cCR following neoadjuvant therapy. Therefore, there remain a lot of controversies regarding the clinical application of neoadjuvant chemoradiotherapy in LARC. In this manuscript, research progress in the indication for neoadjuvant therapy, improvement in the neoadjuvant therapeutic schedule, advancement of the efficacy evaluation criteria of neoadjuvant therapy, the "watch and wait" approach and other hot topics is summarized to provide references for clinical practice.
Antimetabolites, Antineoplastic ; therapeutic use ; Capecitabine ; therapeutic use ; Chemoradiotherapy ; Fluorouracil ; therapeutic use ; Humans ; Neoadjuvant Therapy ; Neoplasm Staging ; Rectal Neoplasms ; therapy ; Treatment Outcome

No abstract available.
Angiogenesis Inhibitors/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Antimetabolites, Antineoplastic/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Deoxycytidine/*analogs & derivatives/therapeutic use ; Drug Resistance, Neoplasm ; Humans ; Pancreatic Neoplasms/*drug therapy/mortality/pathology ; *Salvage Therapy ; Survival Analysis ; Treatment Failure

Pancreatic adenocarcinoma is one of the fatalist malignancies. A large proportion of patients are diagnosed with unresectable stage pancreatic cancer at the time of presentation. Gemcitabine is a standard chemotherapeutic agent since 1997, but survival benefit is not satisfactory. Recent clinical study proved that several new combination chemotherapy regimens are superior to gemcitabine single chemotherapy and extended overall survival. However, its prognosis still remains grim. Current research is taking a multidirectional approach in the hope of developing more effective treatments. This article reviews the major clinical trial data that is the basis for the current chemotherapy regimens used as first- and second-line treatments for advanced pancreatic adenocarcinoma. This article also reviews the current ongoing clinical trials, which include the use of molecular targeting agents and immune therapies.
Adenocarcinoma/*drug therapy/pathology ; Antimetabolites, Antineoplastic/therapeutic use ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Deoxycytidine/analogs & derivatives/therapeutic use ; Humans ; Immunotherapy ; Pancreatic Neoplasms/*drug therapy/pathology ; Protein Kinase Inhibitors/therapeutic use