Her 2 neu metflstatic breast cancer; low dose sequential docetaxel - capecitabine chemotherapy as first line treatment a clinical trial of cancer research group Pakistan

To evaluate the efficacy and toxicity of low dose sequential docetaxel-capecitabine chemotherapy as first line treatment of HER 2 negative metastatic breast cancer [MBC]. Experimental Study, Clinical Trial. Three different oncology centers, collaborating under the Cancer Research Group Pakistan. From June 2006 to December 2007. Female breast cancer patients with visceral or visceral and bone metastases and a KPS > 70 were eligible. Results: 38 patients were enrolled. Median age was 49 years [Range 32-70]. With docetaxel treatment, CR was seen in 06 [16%] patients and PR in 20 [53%] with an overall response rate of 69%. Stable disease was seen in 10 [26%] and PD in 02 [05%]. Four out of six complete responses were in patients with liver metastases. Thirty six patients received capecitabine. Thirty were evaluable for response. Capecitabine added one CR [3.33%] and six partial responses [20%]. Two patients [6.67%] who had a partial response to docetaxel relapsed during capecitabine treatment. As a result at the completion of the therapy CR was seen in 07 patients [18.42%], PR in 23 patients [60.53%] with SD and PD in, 4 patients [10.53%] each. An overall RR of 78.94% was seen. Median time to progression was 10.9 months [range, 3-22 months] and at a median follow up time of 24 months [range, 16 -34 months] 13 patients have died with an overall survival probability of docetaxel -capecitabine sequential therapy of 0.68. Significant docetaxel specific grade 3/4 toxicities included neutropenia and diarrhea in 14 [36.84%] and 03 [07.89%] respectively. Febrile neutropenia was seen in 06 [15.79%]. Capecitabine specific significant grade 3 toxicities included hand-foot syndrome in three patients [8.33%] and diarrhea in 2 [5.56%]. Stomatitis, dermatitis, fatigue was seen in one patient [2.78%] each. This treatment schedule of low dose sequential docetaxel - capecitabine is an effective first line treatment of HER 2 negative MBC that provides good overall response rate, manageable toxicity and improved survival

Variation in sister chromatid exchange frequencies and cell-cycle kinetics between human whole blood and plasma leukocyte cultures

Os efeitos da concentraçäo de bromodeoxiuridine (BUdR) e o comprimento do período de síntese (S) na freqüência basal de intercâmbios de cromátides irmäs (SCEs)e na taxa de proliferaçäo de culturas de sangue total (WBC) e de leucócitos plasmáticos (PLC) humanos foram estudados. Um método imunofluorescente foi usado para induzir a diferenciaçäo de cromátides irmäs. Este método emprega uma baixa concentraçäo de BUdR para a marcaçäo de cromossomos durante o primeiro ciclo celular in vitro (3,3µM), e o anticorpo monoclonal anti-BUdR conjugado com fluoresceína isotiocianada (FITC) para detecçäo. Permitiu-se que WBC e PLC crescessem durante o primeiro ciclo celular (48h) na presença de BUdR; o meio de cultura foi entäo substituído pelo meio de cultura sem BUdR e as células foram cultivadas por um ciclo celular adicional (24h) até a colheita (72h). Os cromossomos foram contrastados com iodeto de propidium DAPI. PLC mostrou no mínimo um aumento em dobro na freqüência de SCE sobre os valores de WBC e a paralela, independente da concentraçäo de BUdR no meio de cultura, pelo menos na faixa do análogo de base empregada (3,3µM-33,0µM). Além disso, uma estimativa do comprimento do período S, feita pela análise da proporçäo de diferentes tempos de colheira, revelou que PLC tem um período S marcadamente extenso, comparado a WBC. Conseqüentemente, a taxa de deslocamento de fork do DNA de linfócitos em PLC poderia ser mais lenta que em WBC, resultando em um aumento na freqüência de SCE destas culturas.