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  • Chlordiazepoxide  (1)
  • performance status  (1)
  • 1
    ISSN: 1432-2072
    Keywords: Morphine ; Rats ; Operant behavior ; Antinociception ; Tolerance ; Chlordiazepoxide ; Cumulative dose-response functions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The development of tolerance to behavioral effects of morphine was investigated in rats that responded on a two-lever, multiple-trial, multiple differential-reinforcement-of-low-rate fixed-ratio (mult DRL FR) schedule of food presentation. Stable performances were maintained when sessions were conducted just twice per week. The effects of cumulative doses of morphine (1.0–8.0 mg/kg) or chlordiazepoxide (CDP; 4.0–32.0 mg/kg) were evaluated once per week; saline injections were given in the intervening sessions. The effects of saline and morphine on nociception were also evaluated in hot-plate tests conducted on the same subjects 15 min after selected operant sessions. Initially, morphine produced dose-related decreases in response rates and reinforcement rates in the DRL and FR components as well as significant increases in hot-plate response latencies. Following weekly administration of morphine (1.0–8.0 mg/kg) for 10 weeks, there was little or no tolerance to its effects on operant behavior. In contrast, complete tolerance developed to the antinociceptive effects of morphine. These results suggest that tolerance to various behavioral effects of morphine may be dissociated, and that the loss of reinforcement may be insufficient by itself to produce tolerance to effects of morphine on operant behavior. Additionally, whereas CDP initially produced only dose-related decreases in DRL and FR response rates, following weekly morphine the smaller doses of CDP (4.0–16.0 mg/kg) produced increases in response rates. Finally, the effects of cumulative doses of morphine did not differ significantly from the effects of noncumulative doses of the drug.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1569-8041
    Keywords: colorectal cancer ; CPT-11 ; oxaliplatin ; pancreatic cancer ; performance status
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:To determine the dose-limiting toxicity of CPT-11 incombination with oxaliplatin, and the maximal tolerated dose (MTD) and therecommended dose (RD) of CPT-11 using an every two weeks schedule. Patients and methods:The study was designed to evaluate escalateddoses of CPT-11 starting at 100 mg/m2 with a fixedclinically-relevant dose of 85 mg/m2 oxaliplatin given every twoweeks. Results:Twenty-three patients and 186 cycles were evaluable fortoxicity (median per patient: 7, range: 1–13). Grade 3oxaliplatin-induced neurotoxicity was cumulative and limiting in 39%(9 of 23) of patients. The MTD of CPT-11 was 200 mg/m2, withincomplete neutrophil recovery at day 15 as limiting toxicity. At the RD (175mg/m2 of CPT-11): no grade 4 neutropenia was seen in the two firstcycles; 30% of patients experienced grade 3–4 diarrhea. Febrileneutropenia (3.2% of all cycles) was 3-fold more frequent inperformance status (PS) 2 than in PS 0–1 patients. Among elevencolorectal cancer (CRC) patients, three complete and four partial responseswere documented, including in three 5-fluorouracil (5-FU) refractory patients. Conclusion:To combine CPT-11 175 mg/m2 and oxaliplatin85 mg/m2 every two weeks is feasible in an outpatient setting, andvery active in 5-FU resistant CRC patients. A dose of 150 mg/m2CPT-11 is recommended in PS 2 patients.
    Type of Medium: Electronic Resource
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