RESUMEN
Taste alteration (dysgeusia), an underrecognized toxicity associated with taxane-based chemotherapy (TaxCh), lacks standard treatment. We investigated prevention of dysgeusia with oral glutamine in patients undergoing first-time TaxCh. Adult patients were randomized to receive either 30 g/day glutamine or placebo (maltodextrin) from day 1 of TaxCh. Dysgeusia was measured daily with a visual analogue scale (VAS). On each chemotherapy cycle, objective (sour, sweet, salty, bitter) and subjective (four-category scale) taste and toxicity (National Cancer Institute Common Toxicity Criteria, v.3) were assessed. Stomatitis and zinc deficiency were treated. For primary outcomes, repeated dysgeusia scores were analyzed with a linear mixed model. Repeated data on each objective or subjective taste item were analyzed with a generalized estimating equation. Of 52 patients randomized, 41 completed treatment (median study duration, 74 days). At baseline, the glutamine (n = 21) and placebo (n = 20) groups were comparable for age (64 years), gender (32% men), tumor types, chemotherapy (docetaxel, 44%; paclitaxel, 56%), schedule (weekly, 78%; 3-weekly, 22%), treatment intention (15% adjuvant), dysgeusia (VAS, 11/100), and taste recognition (88%). Twenty-four patients had peripheral neuropathy grades 1-2; none had grade 3. Glutamine and placebo were not different for maximal dysgeusia and increase from baseline, with an insignificant linear time effect. Separate subgroup analyses for patients with baseline dysgeusia < or =11 or >11 did not alter the results. Objective or subjective taste tests were not different, neither were adverse events. Compared with placebo, oral glutamine did not prevent or decrease subjective taste disturbances or altered taste perception associated with TaxCh. The role of glutamine in supportive care of taxane-associated dysgeusia seems limited.
Asunto(s)
Antineoplásicos/efectos adversos , Disgeusia/tratamiento farmacológico , Glutamina/uso terapéutico , Neoplasias/tratamiento farmacológico , Paclitaxel/efectos adversos , Gusto/efectos de los fármacos , Taxoides/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Docetaxel , Método Doble Ciego , Disgeusia/inducido químicamente , Femenino , Glutamina/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Factores de Riesgo , Taxoides/administración & dosificación , Resultado del TratamientoRESUMEN
BACKGROUND: Dendritic cell (DC)-based immunotherapy is a promising approach to augment tumor antigen-specific T cell responses in cancer patients. However, tumor escape with down-regulation or complete loss of target antigens may limit the susceptibility of tumor cells to the immune attack. Concomitant generation of T cell responses against several immunodominant antigens may circumvent this potential drawback. In this trial, we determined the immunostimulatory capacity of autologous DC pulsed with multiple T cell epitopes derived from four different prostate-specific antigens in patients with advanced hormone-refractory prostate cancer. PATIENTS AND METHODS: Autologous DC of HLA-A*0201(+) patients with hormone-refractory prostate cancer were loaded with antigenic peptides derived from prostate stem cell antigen (PSCA(14-22)), prostatic acid phosphatase (PAP(299-307)), prostate-specific membrane antigen (PSMA(4-12)), and prostate-specific antigen (PSA(154-163)). DC were intradermally applied six times at biweekly intervals followed-in the case of an enhanced immune response-by monthly booster injections. Immune monitoring during the time of ongoing vaccinations (12-59 weeks) included ex vivo ELISPOT measurements, MHC tetramer analysis and in vitro cytotoxicity assays. RESULTS: Of the initial six patients, three qualified for long-term multi-epitope DC vaccination. This regime was tolerated well by all three patients. The vaccination elicited significant cytotoxic T cell responses against all prostate-specific antigens tested. In addition, memory T cell responses against the control peptides derived from influenza matrix protein and tetanus toxoid were efficiently boosted. Clinically, the long-term DC vaccination was associated with an increase in PSA doubling time. CONCLUSIONS: DC-based multi-epitope immunotherapy with repeated boosting in men with hormone-refractory prostate carcinoma is feasible and generates efficient cellular antitumor responses.
Asunto(s)
Antígenos de Neoplasias/inmunología , Vacunas contra el Cáncer/inmunología , Carcinoma/tratamiento farmacológico , Células Dendríticas/trasplante , Inmunoterapia Adoptiva/métodos , Neoplasias de la Próstata/tratamiento farmacológico , Fosfatasa Ácida , Anciano , Antígenos de Superficie/inmunología , Carcinoma/inmunología , Células Dendríticas/inmunología , Proteínas Ligadas a GPI , Glutamato Carboxipeptidasa II/inmunología , Antígenos HLA-A/inmunología , Antígeno HLA-A2 , Humanos , Epítopos Inmunodominantes/inmunología , Masculino , Glicoproteínas de Membrana/inmunología , Persona de Mediana Edad , Proteínas de Neoplasias/inmunología , Antígeno Prostático Específico/inmunología , Neoplasias de la Próstata/inmunología , Proteínas Tirosina Fosfatasas/inmunologíaRESUMEN
GOALS OF WORK: The aim of this study was to evaluate the occurrence of chemotherapy-induced nausea and vomiting (CINV) and its effect on patients' ability to carry out daily life activities following moderately to highly emetogenic, first-cycle chemotherapy in routine practice in cancer centers of four different European countries. PATIENTS AND METHODS: This was a prospective, cross-sectional, nonrandomized, self-assessment study in 249 patients enrolled from cancer centers in Spain, Austria, Germany, and Switzerland. The study population consisted of 78% women, with a mean age of 54. Breast, lung, and ovarian cancers made up 75% of all cancers in the study. Patients received a mean of 2.0 chemotherapy agents and 2.5 antiemetic drugs. MAIN RESULTS: A total of 450 emetic episodes experienced by 243 patients was recorded over 5 days following chemotherapy, with an average of 1.8 episodes per patient (range: 0-28). A higher percentage of patients (38%) suffered from delayed compared to acute emesis (13%). Between 42% and 52% of all patients suffered from nausea (visual analogue scale > or = 5 mm) on any one day, peaking at day 3. Using the Functional Living Index for Emesis (FLIE) questionnaire, 75% of patients with nausea and 50% with vomiting reported a negative impact of these conditions on performance of daily living. CONCLUSIONS: CINV remains a significant problem in routine practice, particularly in the delayed phase posttreatment. Overall, CINV had a negative impact on patients' daily life.