Randomized placebo-controlled evaluation of hydrazine sulfate in patients with advanced colorectal cancer.

PURPOSE: Hydrazine sulfate is a controversial agent that was originally studied in cancer patients approximately 20 years ago. Based on a series of recent trials that suggested that this drug might have utility in cancer patients, we conducted this study. PATIENTS AND METHODS: Patients with metastatic colorectal cancer were randomized to receive hydrazine sulfate or placebo in a double-blinded manner. Protocol patients did not concurrently receive any other systemic antineoplastic treatment. RESULTS: There were 127 assessable patients entered onto this clinical trial. Data from the study showed trends both for poorer survival and for poorer quality of life (QL) in the hydrazine group. There were no significant differences in the two study arms with regard to anorexia or weight loss. CONCLUSION: This trial failed to demonstrate any benefit for hydrazine sulfate.

Aminoglycoside forecasting in neutropenic patients with cancer.

To validate the population pharmacokinetic parameters of aminoglycoside disposition in patients with cancer, a retrospective evaluation of predictive performance of a Bayesian program was performed in 155 patients from 1986 to 1989 who received amikacin, gentamicin or tobramycin. Each patient received 1 of the 3 drugs and had initial drug concentration determination, with a second set of drug concentrations drawn < or = 14 days after the initial dose. Predictions of 64 amikacin, 144 gentamicin and 102 tobramycin concentrations were generated using 1-compartment model pharmacokinetic parameters, serum creatinine values, patients' dosage history and demographic data. The mean (+/- SD) observed (and predicted) serum concentrations for amikacin were 18.9 +/- 14.8 mg/L (17.2 +/- 14.1 mg/L); for gentamicin were 4.49 +/- 3.58 mg/L (4.26 +/- 3.33 mg/L) and for tobramycin were 4.52 +/- 3.70 mg/L (4.05 +/- 3.49 mg/L) [p > 0.05]. Results demonstrated minimal bias with a mean error in gentamicin concentrations of -0.236 (95% CI -0.533: 0.0613). Significant (p < 0.05) under prediction occurred in concentrations of tobramycin [-0.474 mg/L (95% CI -0.842: -0.0107)] and amikacin [-1.77 mg/L (95% CI -3.42: -0.114)]. Good precision is indicated by a mean squared error for gentamicin of 3.35 mg/L (95% CI 1.70: 4.99) and for tobramycin of 3.64 mg/L (95% CI 1.83: 5.44). Fair precision is demonstrated by amikacin [46.1 mg/L (95% CI 27.3: 65.0)]. Similar results were shown in a separate peak/trough analysis. These data indicate that aminoglycoside pharmacokinetics in patients with cancer can be predicted with minimal bias and good precision using a Bayesian forecasting program for gentamicin and tobramycin.

Evaluation of factors associated with stability of anticoagulation therapy.

Eighty-two patients receiving long-term warfarin therapy provided 199.34 patient-years of data that were evaluated to determine if certain variables could identify those who might be monitored safely at less frequent intervals. Most patient demographics, social habits, medical histories, indications for anticoagulation, and concurrent therapy were not useful in discriminating between patients with stable (n = 67) and unstable (n = 15) anticoagulation. A few trends were noted, but they failed to achieve statistical significance. Patients who never achieved stability (the unstable group) tended to be younger than those who did (p 0.13). Among the stable patients, those with a diagnosis of deep vein thrombosis or pulmonary embolus, or with elevated alanine aminotransferase values, were significantly more likely to require a dosage change. The probability of requiring a dosage change at monthly visits did not correlate with the time required to become stable, but it did correlate inversely with the duration of stable anticoagulation. This probability declined from almost 16% when monitoring frequency was first extended to monthly intervals to less than 8% at 2 months of stable anticoagulation, and tended to decline further with longer periods of stable therapy. Of the 67 patients who became stable, 23 did not require a dosage change during an average of 526 days of follow-up. Among the 44 stable patients who required a dosage change, the mean time to the change was 250 days after becoming stable. Few complications occurred, almost all of them early in therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

The safety and effectiveness of long-term warfarin therapy in an anticoagulation clinic.

Whenever long-term anticoagulation is prescribed, the risks of such therapy must be evaluated accurately. Whether these risks are influenced by the duration of therapy, the indication for therapy, patient demographics and social habits, or the use of an anticoagulation clinic is controversial. This study examined the occurrence rates of major hemorrhage, minor hemorrhage, and thromboembolic events among an inception cohort of 82 patients receiving long term-warfarin therapy in an anticoagulation clinic. During 199.34 patient-years of observation, there were 4 major hemorrhages (0.0201/patient-year), 31 minor hemorrhages (0.1555/patient-year), and 7 thromboembolic events (0.0351/patient-year). Although each type of event tended to occur during the first 6 months of therapy, this trend was not statistically significant. Failure to demonstrate statistically significant influence of any of the evaluated variables may have been due to the unusually low rate of complications, a finding that may reflect the safety of anticoagulant therapy when managed by a specialized clinic.

Transdermal fentanyl in the management of cancer pain in ambulatory patients: an open-label pilot study.

We performed an open-label pilot study to define analgesic efficacy, acceptability, and toxicity of transdermal fentanyl in an ambulatory population of patients with cancer pain. Our 7-day study included 35 patients, all of whom had failed a trial of an opioid analgesic conventionally used for moderate pain. Patients received either a 25 micrograms/hr or 50 micrograms/hr fentanyl transdermal patch depending on prior opioid dose. Pain was measured daily utilizing visual analogue (VAS) and categorical (CAT) scales. Hours of nighttime sleep, quality of life, toxicities, and use of rescue medication were also assessed. There was a 24%-29% reduction in mean VAS and CAT pain scores as compared with the baseline and a 25% increase in mean hours of nighttime sleep. Fifty-nine percent of those patients responding (46% of all study patients) were satisfied to very satisfied with the analgesia provided by transdermal fentanyl. Six percent of all study patients were not at all satisfied with the pain relief obtained. Toxicities were similar to those seen with other opioids. No patient developed severe sedation or respiratory depression. The 25-50 micrograms/hr patch appears to be a safe starting dosage in ambulatory patients previously receiving opioids conventionally used for moderate pain.

Hepatic artery chemoembolization therapy for hepatic tumors.

Patients with hepatocellular carcinomas who undergo chemoembolization therapies require skilled perioperative nursing care that addresses their knowledge deficits about chemoembolization techniques, their anxieties related to chemoembolization procedures and adverse effects, and their impaired mobility resulting from the presence of arterial lines and the progression of the cancer. Perioperative nursing participation in chemoembolization procedures is an example of the expanded role of today's OR nurse.

Cancer-related issues for women.

Tobacco and diet account for almost two-thirds of all cancer-related deaths and are among the most correctable risk factors. Up to 35% of cancer-related deaths could be avoided if appropriate screening measures were used. Research on the use of vaccines to treat or prevent cancer has intensified. Pharmacists can play a major role in women's health by acting as patient advocates, serving as referral sources, and recommending supportive care.