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Annals of Oncology : Official Journal... Feb 2021
Topics: Adenocarcinoma; Chemotherapy, Adjuvant; Deoxycytidine; Humans; Pancreatic Neoplasms; Transcriptome; Gemcitabine
PubMed: 33227409
DOI: 10.1016/j.annonc.2020.11.012 -
Clinical Therapeutics Nov 2017Pancreatic cancer has a dismal prognosis due to the early development of systemic metastatic disease. Chemotherapeutic agents are the only systemic therapy that offers... (Review)
Review
PURPOSE
Pancreatic cancer has a dismal prognosis due to the early development of systemic metastatic disease. Chemotherapeutic agents are the only systemic therapy that offers patients meaningful benefit.
METHODS
This study reviewed the literature for recently published Phase III clinical trials whose results have guided the current standards of chemotherapy for pancreatic cancer.
FINDINGS
Although combination chemotherapy regimens are shown to be superior to gemcitabine monotherapy for both metastatic pancreatic cancer and adjuvant chemotherapy after surgical resection, it should be recognized that all combination chemotherapy regimens offer only limited benefits. In addition, there is a paucity of clinical trials that directly compare the various combination chemotherapy regimens.
IMPLICATIONS
With the advancement of systemic cancer treatment beyond chemotherapy, it is important to devote more investigation into better understanding the biology of these chemotherapy regimens, such that we combine them with targeted therapeutics and immunotherapeutics in a rational and scientific manner. For the current treatment of pancreatic cancer, the available chemotherapy regimens have shown modest but statistically significant improvements in survival. However, it is important to avoid cross-comparisons of trials and choose regimens based on patient characteristics and the side-effect profiles of the regimen.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Humans; Pancreatic Neoplasms; Gemcitabine
PubMed: 28939405
DOI: 10.1016/j.clinthera.2017.08.015 -
Acta Haematologica 2019
Topics: Deoxycytidine; Humans; Lymphoma, Non-Hodgkin; Salvage Therapy; Gemcitabine
PubMed: 30630165
DOI: 10.1159/000496098 -
The Oncologist Feb 2007
Review
Topics: Antimetabolites, Antineoplastic; Capecitabine; Clinical Trials as Topic; Deoxycytidine; Fluorouracil; Humans; Neoplasms; Prodrugs
PubMed: 17296810
DOI: 10.1634/theoncologist.12-2-152 -
Journal of Clinical Oncology : Official... Jul 2020
Topics: Adenocarcinoma; Benzimidazoles; Cisplatin; Deoxycytidine; Fanconi Anemia Complementation Group N Protein; Germ Cells; Humans; Mutation; Pancreas; Gemcitabine
PubMed: 32407214
DOI: 10.1200/JCO.20.00833 -
Molecular Pharmaceutics Feb 2013Gemcitabine, an anticancer agent which acts against a wide range of solid tumors, is known to be rapidly deaminated in blood to the inactive metabolite... (Review)
Review
Gemcitabine, an anticancer agent which acts against a wide range of solid tumors, is known to be rapidly deaminated in blood to the inactive metabolite 2',2'-difluorodeoxyuridine and to be rapidly excreted by the urine. Moreover, many cancers develop resistance against this drug, such as loss of transporters and kinases responsible for the first phosphorylation step. To increase its therapeutic levels, gemcitabine is administered at high doses (1000 mg/m(2)) causing side effects (neutropenia, nausea, and so forth). To improve its metabolic stability and cytotoxic activity and to limit the phenomena of resistance many alternatives have emerged, such as the synthesis of prodrugs. Modifying an anticancer agent is not new; paclitaxel or ara-C has been subjected to such changes. This review summarizes the various chemical modifications that can be found in the 4-(N)- and 5'-positions of gemcitabine. They can provide (i) a protection against deamination, (ii) a better storage and (iii) a prolonged release in the cell, (iv) a possible use in the case of deoxycytidine kinase deficiency, and (v) transporter deficiency. These new gemcitabine-based sysems have the potential to improve the clinical outcome of a chemotherapy strategy.
Topics: Animals; Antimetabolites, Antineoplastic; Deoxycytidine; Humans; Kaplan-Meier Estimate; Models, Biological; Phosphorylation; Prodrugs; Gemcitabine
PubMed: 22978251
DOI: 10.1021/mp300370t -
Molecules (Basel, Switzerland) Jan 2021A major obstacle in tumor treatment is associated with the poor penetration of a therapeutic agent into the tumor tissue and with their adverse influence on healthy... (Review)
Review
A major obstacle in tumor treatment is associated with the poor penetration of a therapeutic agent into the tumor tissue and with their adverse influence on healthy cells, which limits the dose of drug that can be safely administered to cancer patients. Gemcitabine is an anticancer drug used to treat a wide range of solid tumors and is a first-line treatment for pancreatic cancer. The effect of gemcitabine is significantly weakened by its rapid plasma degradation. In addition, the systemic toxicity and drug resistance significantly reduce its chemotherapeutic efficacy. Up to now, many approaches have been made to improve the therapeutic index of gemcitabine. One of the recently developed approaches to improve conventional chemotherapy is based on the direct targeting of chemotherapeutics to cancer cells using the drug-peptide conjugates. In this work, we summarize recently published gemcitabine peptide-based conjugates and their efficacy in anticancer therapy.
Topics: Animals; Cell-Penetrating Peptides; Deoxycytidine; Humans; Molecular Targeted Therapy; Nanoparticles; Neoplasms; Peptides; Gemcitabine
PubMed: 33445797
DOI: 10.3390/molecules26020364 -
Annals of Oncology : Official Journal... Dec 1998
Topics: Animals; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Clinical Trials as Topic; DNA Replication; DNA, Neoplasm; Deoxycytidine; Humans; Lung Neoplasms; Neoplasm Recurrence, Local; Neoplasms; Pancreatic Neoplasms; Gemcitabine
PubMed: 9932153
DOI: 10.1023/a:1008498219576 -
Asian Pacific Journal of Cancer... 2014Patients with recurrent or refractory osteosarcoma are considered to have a very poor prognosis, and new regimens are needed to improve the prognosis in this setting.... (Review)
Review
BACKGROUND
Patients with recurrent or refractory osteosarcoma are considered to have a very poor prognosis, and new regimens are needed to improve the prognosis in this setting. Gemcitabine, a nucleoside antimetabolite, is an analog of deoxycytidine which mainly inhibits DNA synthesis through interfering with DNA chain elongation and depleting deoxynucleotide stores, resulting in gemcitabine-induced cell death. Here we performed a systemic analysis to evaluate gemcitabine based chemotherapy as salvage treatment for patients with recurrent or refractory osteosarcoma.
METHODS
Clinical studies evaluating the impact of gemcitabine based regimens on response and safety for patients with osteosarcoma were identified by using a predefined search strategy. Pooled response rates (RRs) of treatment were calculated.
RESULTS
In gemcitabine based regimens, 4 clinical studies which included 66 patients with recurrent or refractory osteosarcoma were considered eligible for inclusion. Systemic analysis suggested that, in all patients, pooled RR was 12.1% (8/66) in gemcitabine based regimens. Major adverse effects were hematologic toxicity, including grade 3 or 4 anemia, leucopenia and thrombocytopenia in gemcitabine based treatment. No treatment related death occurred in gemcitabine based treatment.
CONCLUSION
This systemic analysis suggests that gemcitabine based regimens are associated with mild activity with good tolerability in treating patients with recurrent or refractory osteosarcoma.
Topics: Antimetabolites, Antineoplastic; Bone Neoplasms; Deoxycytidine; Humans; Osteosarcoma; Treatment Outcome; Gemcitabine
PubMed: 25227807
DOI: 10.7314/apjcp.2014.15.17.7159 -
The Journal of Antimicrobial... Feb 2011The use of antiretroviral medications in HIV-negative individuals as pre-exposure prophylaxis (PrEP) is a promising approach to prevent HIV infection. Tenofovir... (Review)
Review
The use of antiretroviral medications in HIV-negative individuals as pre-exposure prophylaxis (PrEP) is a promising approach to prevent HIV infection. Tenofovir disoproxil fumarate (TDF) and emtricitabine exhibit desirable properties for PrEP including: favourable pharmacokinetics that support infrequent dosing; few major drug-drug or drug-food interactions; an excellent clinical safety record; and pre-clinical evidence for efficacy. Several large, randomized, controlled clinical trials are evaluating the safety and efficacy of TDF and emtricitabine for this new indication. A thorough understanding of variability in drug response will help determine future investigations in the field and/or implementation into clinical care. Because tenofovir and emtricitabine are nucleos(t)ide analogues, the HIV prevention and toxicity effects depend on the triphosphate analogue formed intracellularly. This review identifies important cellular pharmacology considerations for tenofovir and emtricitabine, which include drug penetration into relevant tissues and cell types, race/ethnicity/pharmacogenetics, gender, cellular activation state and appropriate episodic or alternative dosing strategies based on pharmacokinetic principles. The current state of knowledge in these areas is summarized and the future utility of intracellular pharmacokinetics/pharmacodynamics for the PrEP field is discussed.
Topics: Adenine; Chemoprevention; Deoxycytidine; Drug Interactions; Emtricitabine; Female; Food-Drug Interactions; HIV Infections; Humans; Male; Organophosphonates; Tenofovir
PubMed: 21118913
DOI: 10.1093/jac/dkq447