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Acta cir. bras ; 37(2): e370204, 2022. graf
Article in English | LILACS, VETINDEX | ID: biblio-1374066


Purpose: To evaluate the protective effect of Cuscuta chinensis Lam. polysaccharides (PCCL) on 5-fluorouracil-(5-FU)-induced intestinal mucositis (IM) in mice. Methods: PCCL was orally administered at a dose of 20 mg·kg­1 for 7 days and its protective effect on 5-FU-induced IM (5-FU, 50 mg·kg­1 for 5 days) was evaluated by monitoring changes in body weight, degree of diarrhea, levels of tissue inflammatory factors (tumor necrosis factor α, interleukin 6, and interleukin 1ß levels), apoptosis rates, and the expression levels of caspase-3, Bax and Bcl-2. Results: The severity of mucosal injury (as reflected by body weight changes, degree of diarrhea, height of villi, and damage to crypts) was significantly attenuated by PCCL administration. PCCL also reduced the levels of tissue inflammatory factors, the apoptosis rate, and the expression of caspase-3 and Bax, and increased Bcl-2 expression. Conclusions: PCCL administration may be significantly protective against 5-FU-induced IM by inhibiting apoptosis and regulating the abnormal inflammation associated with it.

Animals , Mice , Polysaccharides/therapeutic use , Cuscuta/chemistry , Mucositis/drug therapy , Fluorouracil/adverse effects , Protective Agents/analysis
Article in English | WPRIM | ID: wpr-880619


OBJECTIVES@#Neoadjuvant chemotherapy combined with radical surgery has become the treatment model for locally advanced rectal cancer. The purpose of this study was to evaluate the safety and efficacy of postoperative mFOLFOX6 regimen chemotherapy for locally resectable advanced rectal cancer.@*METHODS@#This was a prospective study. A total of 82 patients with locally advanced rectal cancer admitted to Affiliated Nanhua Hospital, University of South China from February 2015 to December 2017 were selected as the subjects. The patients received 4 courses of mFOLFOX6 chemotherapy and underwent surgery within 4-6 weeks after chemotherapy. The incidences of chemotherapy-related adverse reactions, postoperative complications, and clinical pathological reactions were analyzed.@*RESULTS@#In the period from mFOLFOX6 chemotherapy to preoperative, 82 patients with locally advanced rectal cancer was reported chemotherapy-related adverse reactions, including Grade 4 neutropenia (2.4%), catheter related infection (2.4%), and anorexia (2.4%), Grade 3 nausea (2.4%) and anorexia (2.4%), Grade 2 neutropenia (14.6%) and peripheral neuropathy (7.3%). Finally, 76 patients with locally advanced rectal cancer completed surgery, including 56 (73.7%) with anterior rectum resection, 16 (21.1%) with abdominal perineal resection, and 72 (94.7%) with pelvic nerve preservation. A total of 22 (28.9%) patients had surgical complications, including 8 (10.5%) with complications of Grade 3 or above. The complications with high incidence were intestinal obstruction, anastomotic leakage, and sepsis. Among the 76 patients who completed chemotherapy and surgery, T stage was decreased in 28 (36.8%) and N stage was decreased in 44 (57.9%); forty-two (55.3%) were in pathological Stage I, 20 (26.3%) in Stage IIA, 12 (15.8%) in Stage IIB, and 2 (2.6%) in Stage IIIA. Ten patients were suspected of tumor invasion of surrounding organs before chemotherapy, of which 4 patients did not need to extend the resection of surrounding organs after chemotherapy and achieved R0 resection of tumor; 2 in T@*CONCLUSIONS@#Preoperative mFOLFOX6 regimen chemotherapy for locally resectable advanced rectal cancer is a safe and feasible treatment strategy, and it is worthy of clinical application.

Humans , Antineoplastic Combined Chemotherapy Protocols/adverse effects , China , Fluorouracil/adverse effects , Neoadjuvant Therapy , Neoplasm Staging , Prospective Studies , Rectal Neoplasms/surgery , Treatment Outcome
Acta cir. bras ; 35(5): e202000504, 2020. tab, graf
Article in English | LILACS | ID: biblio-1130642


Abstract Purpose 5-flourourasil (5-FU) is commonly used for early intraperitoneal chemotherapy in colorectal or appendiceal cancer patients with peritoneal carcinomatosis. Due to its effect, anastomosis healing can be impaired and leads to anastomotic leakage. In this study, we aimed to investigate the potential healing effect of platelet-rich plasma (PRP) on colonic anastomosis impaired by intraperitoneal 5-flourouracil application. Methods After ten rats were sacrificed for preparing PRP, forty Wistar-albino rats were subjected to colonic anastomosis, and randomly allocated into four groups including 10 rats each. According to receiving PRP and/or 5-FU application, the groups were formed as control (C), 5-FU without PRP (CT), anastomosis with PRP (C-PRP), and 5-FU with PRP (CT-PRP). CT and CT-PRP groups also received 5-FU intraperitoneally on postoperative day 1 (POD 1). All animals were euthanized on pod 7. The body weight change, anastomotic bursting pressure (ABP), tissue hydroxiprolin (TH) and histopathological examination of each group were analyzed. Results 5-FU application significantly reduced ABP levels when compared with group C, C-PRP and CT-PRP (for each comparison, p<0,01). PRP application in CT-PRP group raised the measure of ABP up to the levels of C group. Although tissue hydroxyproline levels (THL) levels of CT-PRP group were found higher than CT group, it was not significant (p=0.112). Microscopically, comparing with CT group, PRP application significantly promoted the healing of colonic anastomosis subjected to 5-FU application by improving tissue edema, necrosis, submucosal bridging and collagen formation (p<0.05). Tissue healing in CT-PRP group was observed as good as the control groups. (C, C-PRP, p=0.181, p=0.134; respectively). Conclusion PRP administration on colonic anastomosis significantly promotes the healing process of anastomosis in rats receiving 5-FU. This result encourages further clinical use of PRP to reduce the frequency of AL in patients receiving EPIC.

Animals , Rats , Wound Healing , Colon , Platelet-Rich Plasma , Fluorouracil/adverse effects , Antimetabolites, Antineoplastic/adverse effects , Anastomosis, Surgical , Rats, Wistar , Hydroxyproline
J. oral res. (Impresa) ; 8(5): 363-369, oct. 31, 2019. tab, graf
Article in English | LILACS | ID: biblio-1248086


Objective: Chemotherapy treatment against cancer produce systemic toxicities, among which are those related to important structures of the stomatognathic system and its functional activity. 5 Fluorouracil (5-FU) and cyclophosphamide (Cf) are drugs widely used in solid tumors and in bone marrow transplantation, respectively. The objective of this work was to evaluate the toxicity of these drugs regarding functional activity of the submandibular glands, by measuring the percentage of glycogen consumption in two experimental models. Material and Methods: 84 male Wistar rats aged three months were used, housed in individual cages, with controlled temperature and lighting and ad libitum diet. They were divided into four experimental groups: 1) Control (C); 2) Treated with 5-FU+leucovorin (LV) at 20 and 10mg/Kg of body weight respectively for five consecutive days; 3) treated with Cf i.p. at 50mg/Kg of body weight for two consecutive days; and 4) rats with paired feeding (PF): for five and two days respectively, the amount administered resulted from the average of the ingested food of groups 2 and 3. Both submandibular glands were excised. The submandibular glycogen concentration was analyzed at initial time (t0) and after 60 minutes of mechanical stimulation (t60). Results: the average variation changed significantly between time 0 and 60 in the groups C and PF. (p-value=0.0001), the 5-FU + LV treatment group had an average concentration higher at t0 than groups C and PF, without significant consumption at T60. While group Cf showed a lower average concentration at time 0 with respect to groups C and PF, without significant consumption at T60. Conclusion: 5-FU+LV and Cf affect the metabolism of carbohydrates, decreasing the use of glycogen as a metabolic substrate. In the present experimental model, the toxicity of these drugs affected the functional activity of the submandibular gland.

Objetivo: el tratamiento de quimioterapia contra el cáncer produce toxicidades sistémicas, entre las que se encuentran las relacionadas con estructuras importantes del sistema estomatognático y su actividad funcional. El 5-fluorouracilo (5-FU) y la ciclofosfamida (Cf ) son fármacos ampliamente utilizados en tumores sólidos y en trasplantes de médula ósea, respectivamente. El objetivo de este trabajo fue evaluar la toxicidad de estos fármacos con respecto a la actividad funcional de las glándulas submandibulares, midiendo el porcentaje de consumo de glucógeno en dos modelos experimentales. Material y Métodos: se utilizaron 84 ratas Wistar machos de tres meses de edad, alojadas en jaulas individuales, con temperatura e iluminación controladas y dieta ad libitum. Se dividieron en cuatro grupos experimentales: 1) Control (C); 2) Tratados con 5-FU+leucovorina (LV) a 20 y 10mg/Kg de peso corporal, respectivamente, durante cinco días consecutivos; 3) tratados con Cf i.p. a 50mg/Kg de peso corporal durante dos días consecutivos; y 4) ratas con alimentación por parejas (PF): durante cinco y dos días respectivamente, la cantidad administrada resultó del promedio de los alimentos ingeridos de los grupos 2 y 3. Ambas glándulas submandibulares fueron extirpadas. La concentración de glucógeno submandibular se analizó en el momento inicial (t0) y después de 60 minutos de estimulación mecánica (t60). Resultados: la variación promedio cambió significativamente entre el tiempo 0 y 60 en los grupos C y PF. (p=0,0001), el grupo de tratamiento 5-FU+LV tuvo una concentración promedio más alta en t0 que los grupos C y PF, sin un consumo significativo en T60. Mientras que el grupo Cf mostró una concentración promedio más baja en el tiempo 0 con respecto a los grupos C y PF, sin un consumo significativo en T60. Conclusión: 5-FU + LV y Cf afectan el metabolismo de los carbohidratos, disminuyendo el uso de glucógeno como sustrato metabólico. En el presente modelo experimental, la toxicidad de estos medicamentos afectó la actividad funcional de la glándula submandibular.

Animals , Rats , Submandibular Gland/physiology , Cyclophosphamide/adverse effects , Fluorouracil/adverse effects , Glycogen/metabolism , Rats, Wistar , Cyclophosphamide/therapeutic use , Fluorouracil/therapeutic use , Antineoplastic Agents
Braz. j. med. biol. res ; 52(3): e8251, 2019. tab, graf
Article in English | LILACS | ID: biblio-984035


Oral mucositis (OM) is a common and dose-limiting side effect of cancer treatment, including 5-fluorouracil (5-FU) and radiotherapy. The efficacy of the therapeutic measures to prevent OM is limited and disease prevention is not fully observable. Amifostine is a cytoprotective agent with a described anti-inflammatory potential. It is clinically used to reduce radiotherapy and chemotherapy-associated xerostomia. This study investigated the protective effect of amifostine on an experimental model of OM. Hamsters were divided into six groups: saline control group (5 mL/kg), mechanical trauma (scratches) of the right cheek pouch; 5-FU (60 and 40 mg/kg, ip, respectively, administered on days 1 and 2); amifostine (12.5, 25, or 50 mg/kg) + 5-FU + scratches. Salivation rate was assessed and the animals were euthanized on day 10 for the analysis of macroscopic and microscopic injury by scores. Tissue samples were harvested for the measurement of neutrophil infiltration and detection of inflammatory markers by ELISA and immunohistochemistry. 5-FU induced pronounced hyposalivation, which was prevented by amifostine (P<0.05). In addition, 5-FU injection caused pronounced tissue injury accompanied by increased neutrophil accumulation, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) tissue levels, and positive immunostaining for TNF-α, IL-1β, and inducible nitric oxide synthase (iNOS). Interestingly, amifostine prevented the inflammatory reaction and consequently improved macroscopic and microscopic damage (P<0.05 vs 5-FU group). Amifostine reduced inflammation and protected against 5-FU-associated oral mucositis and hyposalivation.

Animals , Male , Stomatitis/prevention & control , Xerostomia/prevention & control , Amifostine/therapeutic use , Protective Agents/therapeutic use , Fluorouracil/adverse effects , Inflammation/prevention & control , Stomatitis/chemically induced , Stomatitis/pathology , Xerostomia/chemically induced , Xerostomia/pathology , Cricetinae , Disease Models, Animal , Inflammation/chemically induced , Inflammation/pathology
Rev. Col. Bras. Cir ; 45(5): e1968, 2018. tab, graf
Article in Portuguese | LILACS | ID: biblio-976932


RESUMO Objetivo: examinar os efeitos da sinvastatina na mucosite gástrica e intestinal após o tratamento com 5-fluorouracil (5-FU), determinados pela expressão de citocinas e histologia em ratos. Métodos: ratos pesando 270±15g foram divididos em dois grupos. O grupo 5-FU+salina foi tratado com 5-FU (50mg/kg) mais solução salina a 0,9% por gavagem uma vez ao dia por cinco dias. O grupo 5-FU+sinvastatina foi tratado com 5-FU (50mg/kg), mais sinvastatina (10mg/kg), da mesma forma. Foi feita a eutanásia dos animais no sexto dia. O estômago e o intestino foram fotografados e removidos para exame. Dosagens séricas de TNF-a, IL-1ß, IL-6 e histopatologia (coloração HE) do estômago e intestino foram realizadas. Resultados: o peso corporal diminuiu em ratos no grupo 5-FU+salina. A sinvastatina não inibiu a perda de peso induzida pelo 5-FU. Danos significativos da mucosa no estômago e no jejuno foram observados em ratos que receberam apenas 5-FU. As dosagens séricas de citocinas foram significativamente menores no grupo 5-FU+sinvastatina do que no grupo 5-FU (p<0,05). A sinvastatina causou efeitos protetores significativos contra as lesões da mucosa gástrica e jejunal induzidas por 5-FU. Conclusão: a sinvastatina atenua a mucosite gástrica e intestinal relacionada à terapêutica com 5-FU. Nossos dados encorajam futuros estudos pré-clínicos e clínicos sobre a utilidade das estatinas na prevenção da mucosite gastrointestinal.

ABSTRACT Objective: simvastatin has pleiotropic anti-inflammatory and immunomodulatory effects potentially usefull to prevent chemotherapy-induced gastrointestinal mucositis. Studies on this are scarce. This study aimed to examine the effects of simvastatin on gastric and intestinal mucositis after 5-fluorouracil (5-FU) treatment in rats. Methods: rats weighing 270±18g were divided into two groups. The 5-FU+saline group (5-FU/SAL) rats were treated with 5-FU (50mg/kg) plus 0.9% saline orally (gavage) once daily for five days. The 5-FU+simvastatin (5-FU/SIMV) group was treated with 5-FU (50mg/kg), plus simvastatin (10mg/kg), in the same way. The rats were euthanased on the sixth day, then their stomach and intestine were photographed and removed for exams. Dosages of serum TNF-a, IL-1ß, IL-6 and histopathology were done for stomach and intestine. Results: body-weight was significantly lower in rats treated with 5-FU+saline than the weight loss of the 5-FU/SIMV group rats. TNF-a expression was lower in 5-FU/SIMV group (172.6±18pg/ml) than in 5-FU/SAL (347.5±63pg/ml). Serum IL-1b was lower in 5-FU/SAL group (134.5±23pg/ml) than in 5-FU/SIMV (48.3±9pg/ml). Serum IL-6 was 61.8±15pg/ml in 5-FU/SIMV and 129.4±17pg/ml in 5-FU/SAL groups. These differences were significant (p<0.05). Mucosal damage in stomach and jejunum were observed in rats receiving 5-FU alone. In the stomach and jejunum, simvastatin caused significant protective effects against 5-FU-induced mucosal injury. Conclusion: simvastatin attenuated gastric and intestinal mucositis related to 5-FU therapeutics in animal model. These data encourage forthcoming clinical studies addressing the usefulness of statins in the prevention and treatment of gastrointestinal mucositis.

Animals , Male , Rats , Simvastatin/therapeutic use , Mucositis/prevention & control , Fluorouracil/adverse effects , Anti-Inflammatory Agents/therapeutic use , Biomarkers/blood , Random Allocation , Interleukin-6/blood , Rats, Wistar , Intercellular Signaling Peptides and Proteins/blood , Disease Models, Animal , Mucositis/chemically induced , Mucositis/pathology , Interleukin-1beta/blood , Intestinal Mucosa/drug effects , Intestinal Mucosa/pathology
Braz. j. med. biol. res ; 48(6): 493-501, 06/2015. tab, graf
Article in English | LILACS | ID: lil-748227


Apolipoprotein E (APOE=gene, apoE=protein) is a known factor regulating the inflammatory response that may have regenerative effects during tissue recovery from injury. We investigated whether apoE deficiency reduces the healing effect of alanyl-glutamine (Ala-Gln) treatment, a recognized gut-trophic nutrient, during tissue recovery after 5-FU-induced intestinal mucositis. APOE-knockout (APOE-/-) and wild-type (APOE+/+) C57BL6J male and female mice (N=86) were given either Ala-Gln (100 mM) or phosphate buffered saline (PBS) by gavage 3 days before and 5 days after a 5-fluorouracil (5-FU) challenge (450 mg/kg, via intraperitoneal injection). Mouse body weight was monitored daily. The 5-FU cytotoxic effect was evaluated by leukometry. Intestinal villus height, villus/crypt ratio, and villin expression were monitored to assess recovery of the intestinal absorptive surface area. Crypt length, mitotic, apoptotic, and necrotic crypt indexes, and quantitative real-time PCR for insulin-like growth factor-1 (IGF-1) and B-cell lymphoma 2 (Bcl-2) intestinal mRNA transcripts were used to evaluate intestinal epithelial cell turnover. 5-FU challenge caused significant weight loss and leukopenia (P<0.001) in both mouse strains, which was not improved by Ala-Gln. Villus blunting, crypt hyperplasia, and reduced villus/crypt ratio (P<0.05) were found in all 5-FU-challenged mice but not in PBS controls. Ala-Gln improved villus/crypt ratio, crypt length and mitotic index in all challenged mice, compared with PBS controls. Ala-Gln improved villus height only in APOE-/- mice. Crypt cell apoptosis and necrotic scores were increased in all mice challenged by 5-FU, compared with untreated controls. Those scores were significantly lower in Ala-Gln-treated APOE+/+ mice than in controls. Bcl-2 and IGF-1 mRNA transcripts were reduced only in the APOE-/--challenged mice. Altogether our findings suggest APOE-independent Ala-Gln regenerative effects after 5-FU challenge.

Animals , Female , Male , Antimetabolites, Antineoplastic/adverse effects , Apolipoproteins E/deficiency , Dipeptides/pharmacology , Fluorouracil/adverse effects , Intestinal Mucosa/drug effects , Mucositis/drug therapy , Apoptosis/drug effects , Body Weight , Dipeptides/therapeutic use , Insulin-Like Growth Factor I/analysis , Intestinal Mucosa/pathology , Leukocyte Count , Lymphoma, B-Cell , Mitosis/drug effects , Mucositis/chemically induced , Mucositis/pathology , Random Allocation , Real-Time Polymerase Chain Reaction , Reproducibility of Results , Time Factors , Treatment Outcome
Article in Korean | WPRIM | ID: wpr-58252


BACKGROUND/AIMS: The purpose of this study was to investigate the efficacy and safety of irinotecan based FOLFIRI chemotherapy as a second-line treatment after failure of FOLFOX-4 chemotherapy in patients with advanced gastric cancer. METHODS: Fifty-two patients who were pathologically diagnosed with unresectable gastric cancer and received FOLFIRI chemotherapy after failure of FOLFOX-4 chemotherapy between September 2005 and February 2012 were enrolled in this study. Data were collected by retrospectively reviewing the medical records. The response to chemotherapy was assessed every 3 cycles by World Health Organization criteria and long term survival was analyzed. The toxicities were evaluated for every course of chemotherapy according to National Cancer Institution (NCI) toxicity criteria version 3.0. RESULTS: Median age of the patients was 57 years. Median overall survival (OS) and time to progression (TTP) were 7.8 and 5 months, respectively. The number of patients showing complete remission, partial remission, stable disease, and progressive disease were 0 (0.0%), 9 (17.3%), 30 (57.7%), and 13 (25.0%), respectively. The overall response rate was 17.3%. During a total of 345 cycles, anemia worse than NCI toxicity grade 3 occurred in 2.9%, leukopenia in 20.3%, neutropenia in 12.2%, and thrombocytopenia in 1.5%. Patients with less organ involvement by metastasis, less than 34 U/mL of CA 19-9 and good responsiveness to third cycle of second line chemotherapy were associated with longer OS and TTP. CONCLUSIONS: FOLFIRI chemotherapy has a modest efficacy with acceptable toxicities in patients with advanced gastric cancer as a second-line treatment. Further well-controlled studies are needed to elucidate the efficacy of FOLFIRI chemotherapy as second-line treatment in patients with advanced stomach cancer.

Adult , Aged , Female , Humans , Male , Middle Aged , Anemia/etiology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Camptothecin/adverse effects , Disease Progression , Fluorouracil/adverse effects , Kaplan-Meier Estimate , Leucovorin/adverse effects , Neoplasm Staging , Organoplatinum Compounds/adverse effects , Retrospective Studies , Stomach Neoplasms/drug therapy , Treatment Outcome
Indian J Dermatol Venereol Leprol ; 2014 Spt-Oct ; 80 (5): 427-430
Article in English | IMSEAR | ID: sea-154926


A 55-year-old woman on treatment with capecitabine and paclitaxel for breast carcinoma presented with history of a tingling sensation in her hands and feet with a progressive burning sensation. She also noted discomfort, minimal pain and stiffness while holding objects. On examination, there was patchy hyperpigmentation of both the palms and soles, and the dorsa of hands and feet. This was accompanied by a thickening of the skin more over the knuckles and toes. In addition there was a moist desquamation around the toes and over the palmar creases and a bluish discoloration of the lunulae of both thumbnails. She was diagnosed with hand and foot syndrome and started on pyridoxine and emollients. The finding of keratoderma noted in our patient is not seen commonly in hand and foot syndrome.

Antimetabolites, Antineoplastic/adverse effects , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Female , Fluorouracil/adverse effects , Fluorouracil/analogs & derivatives , Foot , Hand , Humans , Hyperpigmentation/chemically induced , Keratoderma, Palmoplantar/chemically induced , Middle Aged , Paresthesia/chemically induced , Syndrome
Invest. clín ; 55(2): 185-202, jun. 2014. ilus, tab
Article in Spanish | LILACS | ID: lil-749976


Debido a la inespecificidad de los síntomas, el cáncer gástrico (CG) es diagnosticado frecuentemente en etapas avanzadas, lo que da cuenta de los altos índices de mortalidad debido a esta neoplasia a nivel mundial. El esquema de tratamiento adyuvante o neoadyuvante en los países occidentales incluye el uso de fluoropirimidinas citotóxicas y compuestos de platino formadores de aductos en el ADN. La respuesta clínica al tratamiento con estos fármacos depende principalmente de la sensibilidad del tumor, la cual a su vez está condicionada por el nivel de expresión de los blancos terapéuticos y de las enzimas de reparación del ADN. Sumado a esto, algunos polimorfismos de línea germinal en genes asociados al metabolismo y a la respuesta a estos fármacos, han mostrado asociación con respuestas pobres y con el desarrollo de eventos adversos, incluso con resultados fatales. La identificación de biomarcadores genómicos, en la forma de polimorfismos genéticos o la expresión diferencial de genes específicos asociados a la respuesta quimioterapeútica ha sido motivo de intensa investigación como base para la aplicación de la farmacogenómica en el establecimiento de una terapia farmacológica racional y personalizada del CG. Sin embargo, ante la eventual aplicación de la farmacogenómica en el ámbito clínico, es necesario establecer el valor pronóstico real de dichos biomarcadores mediante los estudios de asociación genotipo-fenotipo, así como su prevalencia en el contexto de cada población de pacientes. Estos aspectos son indispensables al evaluar la relación costo-efectividad de la introducción de los productos de la medicina genómica predictiva en el tratamiento del CG.

Gastric cancer (GC) is often diagnosed at later stages due to the lack of specificity of symptoms associated with the neoplasm, causing high mortality rates worldwide. The first line of adjuvant and neoadjuvant treatment includes cytotoxic fluoropyrimidines and platin-containing compounds which cause the formation of DNA adducts. The clinical outcome with these antineoplastic agents depends mainly on tumor sensitivity, which is conditioned by the expression level of the drug targets and the DNA-repair system enzymes. In addition, some germ line polymorphisms, in genes linked to drug metabolism and response to chemotherapy, have been associated with poor responses and the development of adverse effects, even with fatal outcomes in GC patients. The identification of genomic biomarkers, such as individual gene polymorphisms or differential expression patterns of specific genes, in a patient-by-patient context with potential clinical application is the main focus of current pharmacogenomic research, which aims at developing a rational and personalized therapy (i.e., a therapy that ensures maximum efficacy with no predictable side effects). However, because of the future application of genomic technologies in the clinical setting, it is necessary to establish the prognostic value of these genomic biomarkers with genotype-phenotype association studies and to evaluate their prevalence in the population under treatment. These issues are important for their cost-effectiveness evaluation, which determines the feasibility of using these medical genomic research products for GC treatment in the clinical setting.

Humans , Antineoplastic Agents/pharmacokinetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Stomach Neoplasms/drug therapy , Antineoplastic Agents/adverse effects , Antineoplastic Agents/classification , Biomarkers , Biological Transport/genetics , Biotransformation/genetics , Combined Modality Therapy , Drug Combinations , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacokinetics , Deoxycytidine/therapeutic use , Drug Resistance, Neoplasm/genetics , Enzymes/genetics , Ethnicity/genetics , Fluorouracil/adverse effects , Fluorouracil/analogs & derivatives , Fluorouracil/pharmacokinetics , Fluorouracil/therapeutic use , Gastrectomy , Mexico , Molecular Targeted Therapy , Organoplatinum Compounds/pharmacokinetics , Oxonic Acid/pharmacokinetics , Patient Selection , Pharmacogenetics , Precision Medicine , Prodrugs/pharmacokinetics , Stomach Neoplasms/genetics , Stomach Neoplasms/surgery , Tegafur/pharmacokinetics
Arch. med. interna (Montevideo) ; 35(2): 37-47, jul. 2013. ilus
Article in Spanish | LILACS | ID: lil-722865


La cardiotoxicidad por fármacos quimioterápicos es un efecto adverso frecuente y esperado. En este sentido se ha creado una especialización, la cardiooncología, que tiene como principal objetivo la prevención de estos efectos. La forma de expresión de este fenómeno es muy variada, pudiendo manifestarse como: insuficiencia cardíaca, hipertensión arterial, eventos coronarios agudos y/o trastornos del ritmo. La clave en la prevención está en la idividualización del riesgo cardiotóxico de cada paciente (en base a factores reconocidos como edad, sexo, irradiación mediastinal previa, tipo de fármaco, dosis acumulada, cardiopatía asociada previamente) y el riesgo potencial cardiotóxico de cada quimioterápico. En este sentido se han creado algoritmos de actuación fundamentados en la monitorización y el inicio de tratamiento precoz y oportuno de cada efecto, previniendo el mal mayor en cada paciente.

Humans , Male , Female , Antineoplastic Agents/toxicity , Drug-Related Side Effects and Adverse Reactions , Cardiovascular Diseases/etiology , Alkylating Agents , Antibodies, Monoclonal , Antineoplastic Agents, Alkylating/adverse effects , Antineoplastic Agents, Alkylating/toxicity , Antineoplastic Agents/adverse effects , Anthracyclines/adverse effects , Anthracyclines/toxicity , Fluorouracil/adverse effects , Fluorouracil/toxicity , Protein Kinase Inhibitors , Toxoids/adverse effects , Toxoids/toxicity
An. bras. dermatol ; 88(5): 732-738, out. 2013. tab, graf
Article in English | LILACS | ID: lil-689729


BACKGROUND: Actinic keratosis is a frequent lesion which occurs in sunlight exposed areas. Diclofenac sodium and 5-Fluorouracil are effective, non-invasive and easy-to-apply topical treatment options. OBJECTIVES: To assess and compare the effectiveness of 3% diclofenac sodium associated with 2.5% hyaluronic acid and of 5% 5-Fluorouracil for the treatment of actinic keratosis, as well as the patient's degree of satisfaction and tolerability. METHODS: 28 patients with a clinical diagnosis of actinic keratosis were randomized to receive diclofenac sodium or 5-Fluorouracil and were clinically assessed before and after treatment as well as 8 weeks after the end of treatment. Modified versions of the Investigator and Patient Global Improvement Scores were used. RESULTS: The average number of lesions in the diclofenac sodium group before and after treatment was 13.6 and 6.6 (p<0,001), respectively, while it was 17.4 and 3.15 (p<0.001) in the 5-Fluorouracil group. There was a significant reduction in the number of lesions in the 5-Fluorouracil group in relation to the diclofenac sodium group (p<0.001). To the non-blinded physician, there was a higher satisfactory therapeutic response in the 5-Fluorouracil group (p<0.001); to the blinded physician, there was a higher satisfactory response in this same group, although not statistically significant (p=0.09). There was a high degree of satisfaction in both groups (73% in the diclofenac sodium group and 77% in the 5-Fluorouracil group; p=0.827). Regarding adverse effects, the diclofenac sodium group presented a higher degree of satisfaction (93.3% vs 38.4%; p=0.008). Erythema, edema, crusts and itching were significantly higher in the 5-Fluorouracil group. CONCLUSION: We concluded that 5-Fluorouracil was more effective; however, it showed lower tolerability than diclofenac sodium. .

FUNDAMENTOS: Ceratose actínica é uma lesão frequente que ocorre em áreas de exposição solar. Diclofenaco sódico e 5-Fluorouracil são opções de tratamento tópico efetivo, não invasivo e de fácil aplicação. OBJETIVOS: Avaliar e comparar a efetividade do diclofenaco sódico 3% associado ao ácido hialurônico 2,5% e do 5-fluorouracil 5% no tratamento de ceratose actínica, assim como a tolerabilidade e o grau de satisfação do paciente. MÉTODOS: 28 pacientes com diagnóstico clínico de ceratoses actínicas foram randomizados para receber diclofenaco sódico ou 5-fluorouracil e foram avaliados clinicamente antes, ao término e após 8 semanas do tratamento. Utilizou-se o Escore de Melhora Global do Investigador e do Paciente, ambos modificados. RESULTADOS: A média de lesões no grupo do diclofenaco sódico antes e depois do tratamento foi de 13,6 e 6,6 (p<0,001) e no grupo do 5-fluorouracil foi de 17,4 e 3,15 (p<0,001). Houve uma diminuição significativa no número de lesões no grupo do 5-fluorouracil em relação ao grupo do diclofenaco sódico (p<0,001). Para o médico não cegado houve uma resposta terapêutica satisfatoriamente maior no grupo do 5-fluorouracil (p<0,001); para o cegado, houve uma maior resposta nesse mesmo grupo, porém não significativa (p=0,09). Houve alta satisfação com o tratamento em ambos os grupos (73% no diclofenaco sódico e 77% no 5-fluorouracil; p=0,827). Já em relação aos efeitos adversos, o grupo do diclofenaco sódico apresentou taxa de satisfação maior (93,3% vs 38,4%; p=0,008). Eritema, edema, crostas e prurido foram significativamente maiores no tratamento com 5-fluorouracil. CONCLUSÕES: Concluímos que o 5-fluorouracil foi mais efetivo, ...

Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Dermatologic Agents/administration & dosage , Diclofenac/administration & dosage , Fluorouracil/administration & dosage , Keratosis, Actinic/drug therapy , Administration, Cutaneous , Chi-Square Distribution , Dermatologic Agents/adverse effects , Diclofenac/adverse effects , Fluorouracil/adverse effects , Patient Satisfaction , Time Factors , Treatment Outcome
Rev. gaúch. enferm ; 34(3): 110-116, set. 2013. tab
Article in Portuguese | LILACS, BDENF | ID: lil-695263


Objetivou-se avaliar a qualidade de vida (QV) de mulheres com câncer de mama em tratamento quimioterápico e identificar a ocorrência de náuseas e vômitos durante o tratamento. Os dados foram coletados com a aplicação do instrumento da Organização Europeia de Pesquisa e Tratamento de Câncer, EORTC-QLQ-C30, na versão em português, bem como do módulo para câncer de mama BR-23, aplicados antes, no meio e ao final do tratamento. Das 79 mulheres incluídas, 93% apresentaram náuseas e 87% vômitos pelo menos uma vez durante o tratamento. A QV apresentou pequena diminuição durante o tratamento. O coeficiente alfa de Cronbach para cada aplicação dos questionários foi de 0,890492, 0,936392 e de 0,937639. A disponibilidade de informações sobre o tratamento e de orientações quanto ao manejo da náusea e do vômito é crucial para o gerenciamento adequado das toxicidades da quimioterapia.

Evaluar la calidad de vida (QOL) de las mujeres con cáncer de mama durante la quimioterapia e identificar el acontecimiento de náuseas y vómitos durante el tratamiento. Se recogieron datos con la aplicación del instrumento de la Organización Europea para la Investigación y Tratamiento del Cáncer, EORTC-QLQ-C30 versión en portugués y módulo para el cáncer de mama BR-23 aplicado antes, en la mitad y al final del tratamiento. Se incluyeron 79 mujeres, el 93% tuvo náuseas, el 87% vómitos al menos una vez durante el tratamiento. La QOL presentó una ligera disminución durante el tratamiento. El coeficiente alfa de Cronbach para cada aplicación de los cuestionarios fue 0.890492, 0.936392 y 0.937639. La disponibilidad de informaciones sobre el tratamiento y directrices sobre el manejo de la náusea y vómito es fundamental para la correcta gestión de las toxicidades de la quimioterapia.

The aim of this study was to assess the quality of life (QoL) of women with breast cancer during chemotherapy and to identify the incidence of nausea and vomiting during the treatment. Data were assessed with the application of the instrument of the European Organization for Research and Treatment of Cancer, EORTC-QLQ-C30 Portuguese version and breast cancer module BR-23, which was applied before, in the middle and in the end of the treatment. The participants were 79 women, of which 93% had nausea and 87% had vomited at least once during the treatment. QoL showed a slight decrease during treatment. Cronbach's alpha for each application of the questionnaires was 0.890492, 0.936392 and 0.937639. The availability of treatment information and guidelines on the management of nausea and vomiting is crucial for the proper management of the toxicities of chemotherapy.

Adult , Aged , Female , Humans , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/drug therapy , Nausea/chemically induced , Vomiting/chemically induced , Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/nursing , Breast Neoplasms/psychology , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Epirubicin/administration & dosage , Epirubicin/adverse effects , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Nausea/nursing , Nausea/psychology , Prospective Studies , Quality of Life , Surveys and Questionnaires , Severity of Illness Index , Socioeconomic Factors , Taxoids/administration & dosage , Vomiting/nursing , Vomiting/psychology
Indian J Cancer ; 2013 Jan-Mar; 50(1): 58-64
Article in English | IMSEAR | ID: sea-147321


Aims: To compare the clinical and pathologic assessment of response to neoadjuvant chemotherapy and describe the various histopathologic changes observed. Materials and Methods: We studied a group of 40 patients with locally advanced breast cancer who had their initial workup in the form of clinico-imaging assessment of the size and pretreatment biopsy from the lesion. All the patients received two to six cycles of neoadjuvant chemotherapy, either cyclophosphamide 50 to 60 mg/m 2 IV, doxorubicin 40 to 50 mg/m 2 IV and 5-fluorouracil 500 to 800 mg/m 2 IV (CAF) or cyclophosphamide, epirubicin, and 5-fluorouracil (CEF). Clinical and pathologic assessment of response to chemotherapy was done based on the UICC guidelines. Result: Complete clinical response (cCR) was seen in 10% cases (4/40), thirty percent patients had (12/40) partial response and 60% (24/40) had stable disease after neoadjuvant chemotherapy. Pathologic complete response (pCR) with no evidence of viable tumor was observed in 20% patients (8/40). Fifteen patients (37.5%) showed partial response and 42.5% patients (17/40) had a stable disease. No patient progressed during the course of chemotherapy. Changes in the tumor type were observed following chemotherapy, most common being the mucinous change. Histologic changes like dyscohesion, shrinkage of tumor cells, elastosis, collagenization, necrosis, lymphocytic reaction, giant cell response are some of the common observations seen following treatment with neoadjuvant chemotherapy. Conclusion: Pathologic assessment of response to neoadjuvant chemotherapy is a better predictor than the clinical response. The chemotherapy drugs can be modified based on the response observed after 1-2 cycles of neoadjuvant, the response being based on both tumor and patient's responsiveness.

Biomarkers, Pharmacological/metabolism , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Carcinoma, Ductal/drug therapy , Carcinoma, Ductal/pathology , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Disease-Free Survival , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Epirubicin/administration & dosage , Epirubicin/adverse effects , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Middle Aged , Neoadjuvant Therapy , Predictive Value of Tests , Prognosis , Treatment Outcome
Indian J Cancer ; 2013 Jan-Mar; 50(1): 25-30
Article in English | IMSEAR | ID: sea-147316


Objective: The aim of this retrospective study was to find out the role of neo-adjuvant chemotherapy (NACT) in changing the management and outcome of advanced hypopharyngeal cancer patients. Materials and Methods: This is a retrospective analysis of 59 treatment naïve, advanced hypopharyngeal cancer patients presenting to our tertiary care center from April 2010 to October 2011. NACT was given as two (platinum with taxane) or three drug with (platinum, taxane with 5-flurouracil [5 FU]) as 3 weekly regimen with cisplatin and docetaxel as 75 mg/m 2 each, 5-FU as 1000 mg/m 2 . NACT was either given with the intent of achieving: (1) surgical resection (extensive soft tissue disease, oropharyngeal involvement, extensive disease with cartilage erosion) or (2) organ preservation (Bulky disease with inner cartilage erosion, exolaryngeal disease without cartilage erosion, large N3 nodes). Results: The mean age of this population was 55 years. Most (83%) of the patients had pyriform sinus (PFS) involvement. 69% patients had Stage IVa disease, 21% Stage IVb and 10% Stage III. The overall response rate was 66%, including 06% complete responses and 60% partial responses. Following NACT, resectability was achieved in 30% (10/33) and organ preservation protocol was planned after NACT in 73% (19/26) patients. The main toxicities were neutropenia (grade 3, 4, 04%; febrile neutropenia, 4%), mucositis 5%, diarrhea 5%. The median progression free survival was 20 months. Conclusions: NACT can be useful in patients with oropharyngeal involvement to achieve surgical resection and larynx preservation in patients with bulky T3 disease.

Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bridged-Ring Compounds/administration & dosage , Bridged-Ring Compounds/adverse effects , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/therapy , Cisplatin/administration & dosage , Cisplatin/adverse effects , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Follow-Up Studies , Humans , Hypopharyngeal Neoplasms/mortality , Hypopharyngeal Neoplasms/surgery , Hypopharyngeal Neoplasms/therapy , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Neutropenia/etiology , Platinum/administration & dosage , Platinum/adverse effects , Retrospective Studies , Survival Analysis , Taxoids/administration & dosage , Taxoids/adverse effects , Young Adult
Indian J Cancer ; 2013 Jan-Mar; 50(1): 1-8
Article in English | IMSEAR | ID: sea-147312


Impact Factor for 2013 is 1.131 Click here to download free Android Application for this and other journals Click here to view optimized website for mobile devices Journal is indexed with MEDLINE/Index Medicus and Science Citation Index ExpandedShare on facebookShare on twitterShare on citeulikeShare on connoteaShare on googleShare on linkedinMore Sharing Services MINI SYMPOSIUM: HEAD NECK CANCER Year : 2013 | Volume : 50 | Issue : 1 | Page : 1-8 Induction chemotherapy in technically unresectable locally advanced oral cavity cancers: Does it make a difference? VM Patil1, V Noronha1, VK Muddu1, S Gulia1, B Bhosale1, S Arya2, S Juvekar2, P Chatturvedi3, DA Chaukar3, P Pai3, A D'cruz3, K Prabhash1 1 Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India 2 Department of Radio-Diagnosis, Tata Memorial Hospital, Mumbai, Maharashtra, India 3 Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India Date of Web Publication 20-May-2013 Correspondence Address: K Prabhash Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra India DOI: 10.4103/0019-509X.112263 PMID: 23713035 » Abstract Background: Locally advanced and unresectable oral cavity cancers have a poor prognosis. Induction might be beneficial in this setting by reducing tumor bulk and allowing definitive surgery. Aim: To analyze the impact of induction chemotherapy on locally advanced, technically unresectable oral cavity cancers. Materials and Methods: Retrospective analysis of patients with locally advanced oral cavity cancers, who were treated with neoadjuvant chemotherapy (NACT) during the period between June 2009 and December 2010. Data from a prospectively filled database were analyzed for information on patient characteristics, chemotherapy received, toxicity, response rates, local treatment offered, patterns of failure, and overall survival. The statistical analysis was performed with SPSS version 16. Results: 123 patients, with a median age of 42 years were analyzed. Buccal mucosa was the most common subsite (68.30%). Three drug regimen was utilized in 26 patients (21.10%) and the rest received two drug regimen. Resectability was achieved in 17 patients treated with 3 drug regimen (68.00%) and 36 patients receiving 2 drug regimen. Febrile neutropenia was seen in 3 patients (3.09%) receiving 2 drug regimen and in 9 patients (34.62%) receiving 3 drug regimen. The estimated median OS was not reached in patients who had clinical response and underwent surgery as opposed to 8 months in patients treated with non-surgical modality post NACT (P = 0.0001). Conclusion: Induction chemotherapy was effective in converting technically unresectable oral cavity cancers to operable disease in approximately 40% of patients and was associated with significantly improved overall survival in comparison to nonsurgical treatment.

Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bridged-Ring Compounds/administration & dosage , Bridged-Ring Compounds/adverse effects , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Induction Chemotherapy , Male , Middle Aged , Mouth Neoplasms/drug therapy , Mouth Neoplasms/pathology , Mouth Neoplasms/surgery , Neoadjuvant Therapy , Neutropenia/etiology , Platinum/administration & dosage , Platinum/adverse effects , Retrospective Studies , Taxoids/administration & dosage , Taxoids/adverse effects , Young Adult
Pakistan Journal of Pharmaceutical Sciences. 2013; 26 (5): 1013-1022
in English | IMEMR | ID: emr-138424


The purpose of the study is evaluation and assessment of parameters of cardiac toxicity in patients subjected to 5-FU based chemotherapy. Cardiac morbidity is a reported outcome in different 5FU/LV regimens; however none of them are definite or proximate. The bimonthly regimen of high dose leucovorin is reported to be less toxic and more effective as compared to the monthly regimen of low dose leucovorin. We report the detailed assessment of few cardiac parameter of toxicity in patients of advanced colorectal carcinoma subjected to two Schedules of high and low dose Folinic Acid, 5-Fluorouracil, bolus and continuous infusion. The correlation of elevated cardiac biomarkers, angina and hypertension is comparatively assessed in patients with normal general status, hyperglycemia and known cardiac disorders subjected to two different 5FU based chemotherapeutic regimen

Humans , Female , Male , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma/drug therapy , Hypertension/chemically induced , Leucovorin/adverse effects , Heart Diseases/chemically induced , Fluorouracil/adverse effects , Biomarkers/blood , Blood Pressure/drug effects , Prospective Studies , Risk Factors , Time Factors , Treatment Outcome
Article in English | WPRIM | ID: wpr-127493


BACKGROUND/AIMS: Hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil and cisplatin for intractable advanced hepatocellular carcinoma (HCC) may have survival benefits. We aimed to determine the efficacy and safety of HAIC for advanced HCC as first-line therapy. METHODS: A total of 54 patients who received only HAIC with 5-fluorouracil (750 mg/m2 on days 1-4) and cisplatin (25 mg/m2 on days 1-4) for advanced HCC from Jan. 2009 to Dec. 2011 were selected. According to Child-Pugh class, the overall survival (OS), progression-free survival (PFS), and adverse events after HAIC were investigated retrospectively. RESULTS: Median OS and PFS between the Child-Pugh A group (n=24) and the Child-Pugh B/C group (n=30) were 8.7 (95% confidence interval [CI]: 4.7-12.7) vs. 3.7 months (95% CI: 2.0-5.3), and 7.1 (95% CI: 3.8-10.4) vs. 3.6 months (95% CI: 2.0-5.2), respectively. Although median OS and PFS were not statistically significant between the two groups (P=0.079, P=0.196), the Child-Pugh class B/C tended to influence poor OS. Serious adverse events > or = grade 3 occurred frequently in both groups (83.3 vs. 96.7%, P=0.159). Responders (22.2%, complete or partial response) significantly differed in median OS, compared to non-responders (13.1 vs. 4.4 months, P=0.019). Achievement of complete or partial response was an independent prognostic factor of OS (hazard ratio: 0.4, 95% CI: 0.2-0.8, P=0.011). CONCLUSIONS: Achievement of response after HAIC provide a survival benefit in patients with advanced HCC, but HAIC should be administered cautiously in patients with Child-Pugh class B/C, because of a relatively low survival and high incidence of serious adverse events.

Adult , Aged , Female , Humans , Male , Middle Aged , Anemia/etiology , Antineoplastic Agents/adverse effects , Carcinoma, Hepatocellular/drug therapy , Cisplatin/adverse effects , Diarrhea/etiology , Disease-Free Survival , Drug Therapy, Combination , Fluorouracil/adverse effects , Infusions, Intra-Arterial , Kaplan-Meier Estimate , Liver Neoplasms/drug therapy , Neutropenia/etiology , Retrospective Studies , Severity of Illness Index , Thrombocytopenia/etiology , Treatment Outcome
Article in English | IMSEAR | ID: sea-144659


Background & objectives: Interferon alpha 2b (IFNα2b) has been reported to regulate several immune functions efficiently to enhance the cytotoxic activity of NK and T cells towards various forms of tumours. The objective of the present study was to evaluate the efficacy of IFNα2b in overcoming disease induced and/or treatment associated imunosuppression of tongue squamous cell carcinoma (TSCC) patients undergoing chemotherapy for better clinical outcome. Methods: Seven TSCC patients under cisplatin + 5-fluorouracil chemotherapy in combination with IFNα2b were assessed for various immunohaematological parameters before treatment, after chemotherapy and after IFNα2b therapy. Results: Deterioration of the haematological and immune responses was detected in immunosuppressed TSCC patients after chemotherapy. IFNα2b treatment led to a recovery in these parameters in most of the patients. Greater number of T/NK cells and enhanced secretion of type 1 cytokines were also noted. Haematological complications were reduced after completion of the therapy. Immune- and haematostimulation were also observed in patients with partial response. No positive clinical response was detected in one patient. Interpretation & conclusions: IFNα2b appears to be an effective immunostimulator having clinical impact to combat the immunosuppression in TSCC patients. Successful immunostimulation by IFNα2b may help TSCC patients in clinical improvement. The findings of this preliminary study need to be confirmed on a large number of patients with TSCC.

Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/immunology , Cisplatin/adverse effects , Cisplatin/therapeutic use , Flow Cytometry , Fluorouracil/adverse effects , Fluorouracil/therapeutic use , Humans , Immune Tolerance/drug effects , Interferon-alpha/pharmacology , Killer Cells, Natural/drug effects , Killer Cells, Natural/immunology , Recombinant Proteins/pharmacology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , Tongue Neoplasms/drug therapy , Tongue Neoplasms/immunology