Impact of concurrent radiotherapy on chemotherapy total dose and dose intensity in patients with early breast cancer.

AIMS AND BACKGROUND: A retrospective analysis was conducted to evaluate the tolerability as well as the impact of concurrent adjuvant CMF chemotherapy and radiation therapy on total CMF dose and dose intensity. METHODS: The medical records of 59 patients who had received conservative or radical surgery for breast cancer were analyzed. All patients had been assigned to 6 cycles of "1,8 CMF" adjuvant chemotherapy and concomitant radiation therapy. Total drug dose and dose intensity were calculated. Toxicity was recorded scored according to WHO criteria. RESULTS: A total of 355 cycles was administered. Fifty of 59 patients received at least 85% of the programmed chemotherapy total dose, the median value being 100% (range, 42-100). The median relative dose intensity was 0.97 (range, 0.42-1.01). Forty-four of 59 (75%) patients experienced grade 3-4 neutropenia (20 febrile neutropenia) and 29 (49%) required G-CSF support. CONCLUSIONS: This retrospective analysis showed that it is possible to give concurrent CMF and breast radiation while ensuring adequate chemotherapy total doses and dose intensities to most patients. However, G-CSF support is required in a significant proportion of patients.

Human neutrophil oxidative bursts and their in vitro modulation by different N-acetylcysteine concentrations.

Reactive oxygen species released by activated polymorphonuclear leukocytes as an expression of their defensive function are considered to be a major source of the cytotoxic oxidant stress, that triggers a self-sustaining phlogogenic loop in the respiratory system. N-Acetylcysteine (CAS 616-91-1, NAC), a known mucolytic drug, possesses also antioxidant properties, but it undergoes a rapid and extensive first-pass metabolism resulting in low tissue availability. Thus to further improve the NAC bioavailability a single oral administration of 1200 mg NAC has been recently proposed. This study has been performed to investigate in vitro by means of luminol amplified chemiluminescence the ability of the concentration of 35 mumol/l NAC available after single oral administration of 1200 NAC to interfere with human neutrophil oxidative burst evoked by both corpuscolate and soluble stimulants, in comparison with 16 mumol/l NAC, the serum concentration obtainable after single oral administration of 600 mg NAC. At concentrations of 16 and 35 mumol/l, NAC significantly reduced in a concentration-dependent manner the activation of polymorphonuclear neutrophils (PMNs) oxidative bursts induced by all of the stimulants (C. albicans, formyl-methionyl-leucyl-phenylalanine (fMLP), phorbol myristate acetate (PMA)). This effect was also present in cell-free systems, thus confirming the scavenger activity of these two concentrations of NAC. The fact that no effects were seen on PMN phagocytosis and bacterial killing indicates that NAC has no negative influence on other PMN functions such as antimicrobial activity.