OBJECTIVES: To compare the efficacy and safety of two filgrastim formulations for controlling chemotherapy-induced neutropenia and to evaluate the non-inferiority of the test drug relative to the originator. METHODS: This phase III non-inferiority study had a randomized, multicenter, and open-label design. The patients were randomized at a ratio of 1:1 with a follow-up period of 6 weeks for each patient. In both study arms, filgrastim was administered subcutaneously at a daily dose of 5 mg/kg body weight. The primary endpoint was the rate of grade 4 neutropenia in the first treatment cycle. The secondary endpoints were the duration of grade 4 neutropenia, the generation of anti-filgrastim antibodies, and the rates of adverse events, laboratory abnormalities, febrile neutropenia, and neutropenia of any grade. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of the test drug compared with the originator drug; the upper limit of the 90% confidence interval (CI) for the rate of neutropenia between the two groups (12.61%) was lower than the established margin of non-inferiority. The two treatments were similar with respect to the secondary endpoints and safety. CONCLUSION: The efficacy and safety profile of the test drug were similar to those of the originator product based on the rate of grade 4 neutropenia in the first treatment cycle. This study supports Anvisa’s approval of the first biosimilar drug manufactured by the Brazilian industry (Fiprima¯).

OBJETIVOS: Correlacionar a presença de recidiva local de câncer de mama com a expressão de CD105 em carcinomas primários de mama, e a expressão da ciclooxigenase-2 nos carcinomas primários de mama e nos respectivos linfonodos axilares. MÉTODOS: Estudo com uma coorte histórica de 72 mulheres entre 29 e 67 anos com diagnóstico de carcinoma ductal infiltrante de mama, estadio II, tipo histológico não especial com seus linfonodos axilares respectivos, que tiveram diagnóstico e tratamento cirúrgico no Hospital Nossa Senhora da Conceição, no período de 2001 a 2002. Análise imunoistoquímica do CD105 e COX-2 no tumor primário, da COX-2 nos linfonodos axilares e da recidiva local. RESULTADOS: Das 72 mulheres analisadas com tumores primários, 40 tinham linfonodos axilares positivos e 32 eram negativos; para cada tumor primário, foi escolhido apenas um linfonodo axilar. O grau histológico dos tumores foi I (n=4), II (n=41) e III (n=27). Quinze pacientes apresentaram recidiva local em um período médio de 26 meses (IC 95% 24-28). A presença da COX-2 nos tumores primários foi verificada em 52 casos, e a presença de CD105 em 34 casos, mas não foram considerados fatores prognósticos independentes para recidiva (p=0,203 e p=0,145, respectivamente). A sobrevida para pacientes com expressão da COX-2 em linfonodos axilares (metastáticos ou não metastáticos) foi de 19 meses, contra 28,3 meses para pacientes COX-2 negativa (p<0,0001). CONCLUSÃO: A expressão positiva da COX-2 em linfonodos axilares (positivos ou não) parece ser um fator prognóstico independente para sobrevida livre de doença.

OBJECTIVE: To verify the expression of CD105 in primary breast cancer, and the expression of cyclooxygenase-2 in primary breast cancer and in the respective axillary lymph nodes. METHODS: Seventy two women from 18 to 80 years of age, with a diagnosis of Ductal Infiltrative Breast Cancer, stage II, histological type non special, with their respective axillary lymph nodes were submitted to surgical treatment at the "Hospital Nossa Senhora da Conceição" between 2001 and 2002. Immunohistochemical analyses of CD 105 in the primary breast cancer and of COX 2 in the local axillary lymph node were compared for local recurrence. RESULTS: Of the 72 patients with primary tumors, 40 had positive axillary lymph nodes, while 32 were negative. For each primary tumor, only one lymph node was analyzed. . Fifteen patients had local recurrence after 26 months (CI 95% 24-28). Presence of COX-2 in the primary tumors was verified in 52 cases, and presence of CD105 in 34 cases. These independent prognostic factors were not correlated to local recurrence (P= 0.203 e P=0.145, respectively). The period free of local recurrence for patients with positive expression of COX-2 in axillary lymph nodes (with metastasis or not) was of 19 months, while patients with negative expression had a 28.3 months long period free of local recurrence. CONCLUSION: The positive expression of COX-2 in axillary lymph nodes (either positive or negative) seems to be an independent prognostic factor for local recurrence.