PURPOSE: We performed a phase I/II dose-escalation trial of cyclophosphamide, mitoxantrone, and 5-fluorouracil (CNF) in combination with human recombinant granulocyte-colony-stimulating factor (G-CSF, filgrastim) in patients with advanced breast cancer. The objectives of this trial were (1) to gain experience with filgrastim given to patients with advanced breast cancer and receiving standard-dose CNF, and (2) to determine the maximum tolerated dose of CNF that could be given with filgrastim support by incremental dose escalation of two components of the CNF regimen, cyclophosphamide and mitoxantrone. METHODS: Four patients who had received prior therapy for advanced disease received standard-dose CNF with filgrastim support. Sequentially enrolled patients who had received no prior chemotherapy for advanced disease were treated with standard-dose CNF without filgrastim (5 patients), standard-dose CNF with filgrastim (15 patients), or were entered into sequential cohorts of 3-6 patients to be treated with increasing doses of CNF with filgrastim support (29 patients). RESULTS: The maximum tolerated doses that could be given with filgrastim support were 1500 mg/ml cyclophosphamide, 20 mg/m2 mitoxantrone, and 500 mg/m2 5-FU. Overall, 7 complete (14%) and 13 partial responses (26%) were observed. Despite the use of filgrastim, repeated cycles of CNF at doses of 2000 mg/m2 cyclophosphamide, 25 mg/m2 mitoxantrone, and 500 mg/m2 5-FU could not be given because of neutropenia and thrombopenia. Among 18 patients with bidimensionally measurable disease there were 3 complete (17%) and 5 partial (28%) responses. The median progression-free survival of all patients was 236 days (34 weeks). CONCLUSION: The use of filgrastim allows CNF to be given at approximately twice the dose intensity of "standard"-dose CNF. Because nonhematopoietic toxicity was not dose-limiting, further dose escalation of this regimen might be possible with more effective hematopoietic support. The response rate and survival of patients treated in this study were within the range expected with standard-dose chemotherapy.

Adult↗

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The activation in vitro of porcine pancreatic prophospholipase A2 by lysosomal enzymes.

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Animals↗

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Electroencephalographic power spectrum analysis as a monitor of anesthetic depth in horses.

Electroencephalographic (EEG) power spectrum analysis was performed in 18 conscious, adult horses for evaluation as control values for EEG data obtained during anesthesia. Computer-processed total amplitudes for the frequency range 0 to 32 Hz were mainly between 400 and 600 microV, with 80% spectral edge frequency between 16.6 and 32.5 Hz. The highest electrical activity was in the delta band (41.3 +/- 4.4% of total amplitude); there was a less pronounced activity in the beta (34.2 +/- 5.2%), theta (13.6 +/- 1.5%), and alpha (10.0 +/- 1.0%) bands. The applicability of EEG power spectrum analysis as a guide to depth of anesthesia was evaluated in four horses by comparing simultaneously recorded EEG data and clinical signs of anesthesia. Global changes in cerebrocortical electrical activity were detected with a single, monopolar (left frontoatlanto-occipital) EEG lead. Increasing depth of halothane anesthesia was accompanied by a pronounced shift in EEG activity from beta to theta and delta frequency bands, a decrease in 80% spectral edge frequency from 21.5 +/- 2.4 Hz to 12.6 +/- 2.2 Hz, a reduction in the beta/delta ratio of fractional amplitudes from 2.37 +/- 0.84 to 0.49 +/- 0.04, and a slight inconsistent increase in total amplitude from 96.1 +/- 37.3 microV to 185.5 +/- 53 microV. These results show that changes in the clinical signs of anesthetic depth in horses can be described numerically by use of EEG power spectrum analysis.

Anesthesia, General↗