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  • 1
    ISSN: 1432-0843
    Keywords: Cisplatin ; 5-Fluorouracil ; Interferon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To determine the maximum tolerated dose (MTD) of escalating doses of interferon-α-2b (IFN, Intron A) with 5-fluorouracil (5-FU) and cisplatin (DDP) in patients with advanced cancer, 15 patients were accrued between May 1990 and July 1991. Primary sites were unknown (3), colorectal (3), head and neck (2), lung (2), gynecologic (1), gallbladder (1), sarcoma (1), anal canal (1) and pancreas (1). IFN was given s.c. on days 1–5 and then three times weekly with DDP (75 mg/m2, day 1) and 5-FU [750 mg/m2, days 1–5, continuous infusion (CI) on a 28-day cycle. The first two patients treated at level I (3×106 U/m2 s.c.) experienced possible neurotoxic deaths [massive cerebrovascular accident (CVA) and metabolic encephalopathy], and patient 3 had a grade 4 toxicity of performance status decline. Analysis of these events led us to exclude the enrollment of patients on i.v. morphine and of those with prior exposure to DDP. This resulted in grade 3 toxicity in terms of nausea, vomiting, fatigue and leukopenia but in no further CNS event. All patients were evaluable for toxicity but only ten were evaluable for response. Only two partial responses were seen, one in a patient with an unknown primary tumour and one in a patient with head and neck cancer. The combination of IFN is possible with 5-FU and DDP. The recommended dose of IFN is 2×106 U/m2 s.c. in patients with no prior exposure to DDP or i.v. morphine, given together with 5-FU (750 mg/m2, days 1–5, CI) and DDP (75 mg/m2, day 1) on a 28-day cycle.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0843
    Keywords: Key words Ifosfamide enantiomers ; N-Dechloroethylation ; Metabolism ; Enantioselective pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The pharmacokinetics of the R and S enantiomers of ifosfamide (IFF) and of its 2- and 3-N-dechloroethylated metabolites (2-DCE-IFF and 3-DCE-IFF) were investigated in 14 cancer patients treated with a 3-h infusion of (R,S)-IFF (3 g/m2) with mesna uroprotection. An enantioselective gas chromatographic-mass spectrometric (GC-MS) assay was used to determine the concentrations in plasma and urine. The AUCs of (R)-IFF were significantly larger than those of (S)-IFF (2480±200 vs 1960±150 μM . h). The terminal half-lives (7.57±0.99 h) and mean residence times (11.17±1.10 h) of (R)-IFF were significantly longer than those of (S)-IFF, 6.03±0.82 h and 9.37±0.88 h, respectively. The mean volume of distribution at steady state of (R)-IFF (25.68±0.80 l/m2) was slightly smaller than that of (S)-IFF (27.35±0.89 l/m2). While the renal clearances of (R)-IFF and (S)-IFF were similar, the nonrenal clearance was significantly lower for (R)-IFF (30.20±2.70 vs 41.40±3.55 ml/m2 per min) as was total clearance (41.52±2.90 vs 52.37±3.75 ml/m2 per min). The AUC values for all of the DCE metabolites from (S)-IFF were significantly greater than those from (R)-IFF with 47% of the measured AUC accounted for by DCE from (S)-IFF compared to only 20% for (R)-IFF. Therefore, the enantioselective difference in IFF elimination can be partially explained by differences in N-dechloroethylation.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0843
    Keywords: Key words Cisplatin ; 5-Fluorouracil ; Interferon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To determine the maximum tolerated dose (MTD) of escalating doses of interferon-α-2b (IFN, Intron A) with 5-fluorouracil (5-FU) and cisplatin (DDP) in patients with advanced cancer, 15 patients were accrued between May 1990 and July 1991. Primary sites were unknown (3), colorectal (3), head and neck (2), lung (2), gynecologic (1), gallbladder (1), sarcoma (1), anal canal (1) and pancreas (1). IFN was given s.c. on days 1–5 and then three times weekly with DDP (75 mg/m2, day 1) and 5-FU [750 mg/m2, days 1–5, continuous infusion (CI) on a 28-day cycle. The first two patients treated at level I (3×106 U/m2 s.c.) experienced possible neurotoxic deaths [massive cerebrovascular accident (CVA) and metabolic encephalopathy], and patient 3 had a grade 4 toxicity of performance status decline. Analysis of these events led us to exclude the enrollment of patients on i.v. morphine and of those with prior exposure to DDP. This resulted in grade 3 toxicity in terms of nausea, vomiting, fatigue and leukopenia but in no further CNS event. All patients were evaluable for toxicity but only ten were evaluable for response. Only two partial responses were seen, one in a patient with an unknown primary tumour and one in a patient with head and neck cancer. The combination of IFN is possible with 5-FU and DDP. The recommended dose of IFN is 2×106 U/m2 s.c. in patients with no prior exposure to DDP or i.v. morphine, given together with 5-FU (750 mg/m2, days 1–5, CI) and DDP (75 mg/m2, day 1) on a 28-day cycle.
    Type of Medium: Electronic Resource
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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