RESUMO
Neoadjuvant chemotherapy has practical and theoretical advantages over adjuvant chemotherapy strategy in breast cancer (BC) management. Moreover, metronomic delivery has a more favorable toxicity profile. The present study examined the feasibility of neoadjuvant metronomic chemotherapy in two cohorts [HER2+ (TraQme) and HER2− (TAME)] of locally advanced BC. Twenty patients were prospectively enrolled (TraQme, n=9; TAME, n=11). Both cohorts received weekly paclitaxel at 100 mg/m2 during 8 weeks followed by weekly doxorubicin at 24 mg/m2 for 9 weeks in combination with oral cyclophosphamide at 100 mg/day (fixed dose). The HER2+ cohort received weekly trastuzumab. The study was interrupted because of safety issues. Thirty-six percent of patients in the TAME cohort and all patients from the TraQme cohort had stage III BC. Of note, 33% from the TraQme cohort and 66% from the TAME cohort displayed hormone receptor positivity in tumor tissue. The pathological complete response rates were 55% and 18% among patients enrolled in the TraQme and TAME cohorts, respectively. Patients in the TraQme cohort had more advanced BC stages at diagnosis, higher-grade pathological classification, and more tumors lacking hormone receptor expression, compared to the TAME cohort. The toxicity profile was also different. Two patients in the TraQme cohort developed pneumonitis, and in the TAME cohort we observed more hematological toxicity and hand-foot syndrome. The neoadjuvant metronomic chemotherapy regimen evaluated in this trial was highly effective in achieving a tumor response, especially in the HER2+ cohort. Pneumonitis was a serious, unexpected adverse event observed in this group. Further larger and randomized trials are warranted to evaluate the association between metronomic chemotherapy and trastuzumab treatment.
Assuntos
Humanos , Descontaminação/métodos , Geobacillus stearothermophilus/efeitos dos fármacos , Peróxido de Hidrogênio/administração & dosagem , Controle de Infecções/métodosRESUMO
Neoadjuvant chemotherapy has practical and theoretical advantages over adjuvant chemotherapy strategy in breast cancer (BC) management. Moreover, metronomic delivery has a more favorable toxicity profile. The present study examined the feasibility of neoadjuvant metronomic chemotherapy in two cohorts [HER2+ (TraQme) and HER2- (TAME)] of locally advanced BC. Twenty patients were prospectively enrolled (TraQme, n=9; TAME, n=11). Both cohorts received weekly paclitaxel at 100 mg/m(2) during 8 weeks followed by weekly doxorubicin at 24 mg/m(2) for 9 weeks in combination with oral cyclophosphamide at 100 mg/day (fixed dose). The HER2+ cohort received weekly trastuzumab. The study was interrupted because of safety issues. Thirty-six percent of patients in the TAME cohort and all patients from the TraQme cohort had stage III BC. Of note, 33% from the TraQme cohort and 66% from the TAME cohort displayed hormone receptor positivity in tumor tissue. The pathological complete response rates were 55% and 18% among patients enrolled in the TraQme and TAME cohorts, respectively. Patients in the TraQme cohort had more advanced BC stages at diagnosis, higher-grade pathological classification, and more tumors lacking hormone receptor expression, compared to the TAME cohort. The toxicity profile was also different. Two patients in the TraQme cohort developed pneumonitis, and in the TAME cohort we observed more hematological toxicity and hand-foot syndrome. The neoadjuvant metronomic chemotherapy regimen evaluated in this trial was highly effective in achieving a tumor response, especially in the HER2+ cohort. Pneumonitis was a serious, unexpected adverse event observed in this group. Further larger and randomized trials are warranted to evaluate the association between metronomic chemotherapy and trastuzumab treatment.
Assuntos
Administração Metronômica , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Terapia Neoadjuvante , Receptor ErbB-2 , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/química , Carcinoma Ductal de Mama/patologia , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Síndrome Mão-Pé/etiologia , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Gradação de Tumores , Paclitaxel/administração & dosagem , Pneumonia/etiologia , Estudos Prospectivos , Receptores de Estrogênio/análise , TrastuzumabRESUMO
1. The CARDIAC study, a world-wide cross-sectional epidemiological study on the relationship between alimentary factors and cardiovascular diseases, provided the initial evidence of ethnic differences in salt sensitivity; this was because despite much less urinary sodium excretion in Tanzania than in Brazil and the Japanese, the prevalence of hypertension was relatively higher in Tanzania than in the latter two populations. 2. To investigate this difference in salt sensitivity, a standardized clinical experiment was carried out: six to 13 male volunteers were placed on 2500 kcal basal diets containing 3 g salt/day. Eighteen grams of salt were added daily from the sixth to the 11th day in Tanzania and Brazil, while 22 g of salt were added in Japan. 3. Salt loading induced a significant rise in systolic blood pressure (SBP) on the second day of the high salt period (HSP) in Japan, the second and third day of HSP in Brazil, and all days of HSP in Tanzania. 4. Salt sensitivity was seen in 16.7% of the participants in Japan, 36.4% in Brazil and 46.2% in Tanzania. Further analysis of the effect of salt on blood pressure (BP) was carried out using the data from the CARDIAC study by multiple regression analysis. A within-centre comparison of fatty acid was also made. 5. The regression analysis revealed that the relationship of salt and blood pressure is more positively tight in Tanzania than Brazil and Japan after controlling for other confounding variables. Fatty acids in serum phospholipids contain significantly more palmitic acid and showed lower P/S ratios than those from Brazil and Japan.