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Biomedical subjects

B F Issell

Publications and source records attributed to B F Issell.

At least 37 records · Page 2Linked to original sources
PubMed1983

Disposition of orally administered 14C-prednimustine in cancer patients.

A single oral solution dose (40 mg/m2) of 14C-prednimustine was administered to each of four cancer patients. Plasma, urine, and feces were collected at appropriate times and analyzed for total radioactivity. Plasma samples were analyzed for prednimustine. Peak plasma levels of radioactivity (1-3 micrograms 14C-prednimustine equivalents) occurred at 1.5-3 h in three patients and at 5-6 h in one patient. No intact prednimustine was detected in the plasma; this means that if present, it would be at a concentration of 0.02 micrograms/ml or less and would account for less than 1% of the total drug-related material at the time of peak plasma levels. Solvent-extractable metabolites had a plasma half-life of about 8 h or less. By 24 h essentially all the plasma radioactivity appeared to be covalently bound, and it was eliminated slowly with an estimated terminal elimination half-life of about 10 days. Rapid urinary excretion occurred in the first 24 h, and 40%-60% of the dose was recovered in the urine in 72 h. Although prednimustine was well absorbed, the ester was subject to extensive presystemic metabolism and was not present in the systemic circulation after oral administration.

Adenocarcinoma↗
PubMed1982

The podophyllotoxin derivatives VP16-213 and VM26.

VP16-213 and VM26 are compounds with definite anticancer activity in specific tumor types. Despite 10 years of clinical development the full impact of these compounds in current cancer therapy requires further study. There is no conclusive evidence that one compound is superior to the other in any specific tumor type. The composite activities suggest possible differences in certain cancers such as small cell anaplastic lung cancer, lymphoma, leukemia, bladder and ovarian cancer, but sufficiently adequate studies to determine this have not been reported for any tumor. Understanding the basic pharmacology of these compounds should also be considered of high priority since it is obvious that there is much to learn in this area and further clarification should allow improved clinical utilization. It is hoped that the presentations and discussions of the First International Symposium will generate a new wave of interest in future podophyllotoxin research and development.

Animals↗
PubMed1982

Etoposide (VP16-213) and teniposide (VM26) comparative in vitro activities in human tumors.

In order to determine if any inherent sensitivity differences may exist between VP16-213 and VM26 individual human tumors were grown in vitro and drug sensitivities were determined using the soft agar clonogenic assay method. Only nine of the 34 tumors tested so far showed a differing sensitivity to VP16-213 and VM26 as measured by a 25% or greater colony number reduction. However in none of these tumors did this added reduction result in a 70% decrease over control plate colony numbers. As yet we have been unable to demonstrate any clinically meaningful inherent in vitro sensitivity difference between VP16-213 and VM26 in any tumor type tested.

Antineoplastic Agents↗
PubMed1982

Dibromodulcitol plus bleomycin compared with bleomycin alone in head and neck cancer.

Advanced recurrent squamous cell head and neck cancer patients were prospectively randomized to receive or not receive dibromodulcitol 10 mg/kg PO weekly for 8 consecutive weeks in addition to bleomycin chemotherapy. Patients initially entered in the study received bleomycin 15 mu/m2 three times weekly for 8 weeks. This was later changed to 15 mu/m2 twice weekly for 8 weeks because of unacceptable stomatitis. Most patients had relapsed following surgery and/or radiotherapy, but none had received prior chemotherapy. A2 : 1 randomization in favor of the dibromodulcitol-containing therapy was used. There were 12 partial responses in the 44 evaluable patients receiving the combination (27%), and 4 partial responses in the 18 patients receiving single-agent bleomycin chemotherapy (22%). This difference was not statistically significant. Response durations were also relatively short for both therapies. Within the limitations of this study, we were unable to demonstrate that patient benefit resulted from the addition of dibromodulcitol to bleomycin chemotherapy for this patient population.

Adult↗
PubMed1982

A phase I and clinical pharmacology study of intravenously administered carminomycin in cancer patients in the United States.

Carminomycin (CMN) was administered i.v. to 44 patients with a variety of nonhematological cancers every 4 weeks at doses of 15, 20, 22.5, and 25 mg/sq m. Granulocytopenia was the dose-limiting toxicity. The median granulocyte count for previously untreated patients receiving 22.5 mg/sq m was 0.962 cells/microliters, and for previously treated patients receiving 20 mg/sq m it was 0.420 cell/microliters. Moderate to severe phlebitis was associated with drug administration in 50% of cases. Nausea, vomiting, and alopecia were mild. Three of nine patients who received a total CMN dose of greater than or equal to 100 mg/sq m (mean, 132 mg/sq m) developed unexplained decreases in radionuclide cardiac ejection fraction, with one patient developing decreased QRS amplitude and congestive heart failure at a total dose of 160 mg/sq m. CMN is rapidly metabolized to carminomycinol. The elimination half-lives of CMN and carminomycinol are 6 to 10 and 50 hr, respectively. CMN was found to be a more potent inhibitor of human granulocyte-macrophage colony-forming units than was carminomycinol. Objective partial responses were seen in two of seven previously untreated patients with non-small cell lung cancer and one of three patients with squamous cell carcinoma of the head and neck previously untreated with chemotherapy.

Adult↗
PubMed1981

Serum zinc levels in lung cancer patients.

Serum zinc concentrations were determined in 26 extensive squamous cell lung cancer patients and were tested for correlations with survival, response to therapy, nutritional status indices, and various host defense characteristics. Subnormal serum zinc levels were found in 24 of the 26 patients. The mean serum zinc concentration was 43.2/micrograms 100 ml +/- 3.6 S.E.M. (normal = 80-100 micrograms/100 ml). A significant (P = 0.007) survival advantage was demonstrated for those patients with pretreatment zinc concentrations greater than 45 micrograms%, but serum zinc levels did not correlate with response to chemotherapy (also significantly affecting survival). Decreased serum zinc concentrations were significantly associated with decreased neutrophil migration measured by the skin window technique and with decreased triceps skin fold thickness but not with any of the other host defense and nutritional induces measured. These data suggest that further studies are indicated to examine the role of serum zinc concentration as a possible sensitive prognostic characteristic and to determine if zinc administration may be of therapeutic benefit in cancer patients.

Adult↗
PubMed1981

Zinostatin and doxorubicin. A combination phase I study.

Because of encouraging single-agent activity for both zinostatin and doxorubicin in hepatocellular cancer, a phase I tolerance study with these drugs in combination was undertaken. The dose of zinostatin given daily for 5 consecutive days and repeated every 6 weeks was fixed at 2250 units/M2. The starting dose of doxorubicin was 45 mg/m2 on days 1 and 22 of every 6-week cycle, but this was escalated or deescalated by increments of 33% as tolerated. The occurrence of unpredictable severe and prolonged cumulative myelosuppressive toxicity in most patients resulted in considerable management difficulties. In addition, three patients developed congestive heart failure at cumulative doxorubicin doses ranging from 195 to 270 mg/m2 and two patients developed possible drug-related nephrotoxicity. Until reasons for the pharmacogenetic variability observed with zinostatin are defined, combination studies employing this drug are not recommended.

Antibiotics, Antineoplastic↗
PubMed1980

Amsacrine (AMSA).

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Aminoacridines↗
PubMed1980

Mezlocillin for treatment of infections in cancer patients.

Mezlocillin, at a dose of 3 g intravenously over a 2-h period every 4 h, was used for the treatment of 92 episodes of documented infections in 75 myelosuppressed cancer patients. The response rate in 59 evaluable bacterial infections was 46%. Eight of 23 patients with septicemia (35%) responded. The response rates for Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli, the three most common gram-negative infections, were 42, 64, and 70%, respectively. Mezlocillin was well tolerated; the only toxicity attributable to this antibiotic was a skin rash in one patient. The formation of a false-positive urine protein reaction by mezlocillin was noted. This study demonstrated that mezlocillin administered as a single agent was effective against some infections in myelosuppressed cancer patients. The response rate for Klebsiella sp. infections was especially encouraging. However, because it had limited or little activity against many infections, especially those caused by P. aeruginosa and Staphylococcus aureus, the general use of mezlocillin as a single agent for treatment of infections in immunocompromised cancer patients cannot be recommended.

Adolescent↗
PubMed1978

Maytansine.

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Animals↗
PubMed1978

Clinical pharmacology of mezlocillin.

Mezlocillin is a new broad-spectrum semisynthetic penicillin that has shown encouraging in vitro activity against the infecting organisms most likely to cause mortality and morbidity in cancer patients receiving chemotherapy. The serum clearances and urine recoveries of mezlocillin, ampicillin, and carbenicillin were compared after the intravenous administration of single 3-g doses. The peak mean serum concentrations of mezlocillin and carbenicillin were 269 and 278 mug/ml, respectively, whereas the peak ampicillin level was lower at 167 mug/ml. The terminal half-life of mezlocillin, 66 min, was not significantly different from those of ampicillin and carbencillin (63 and 77 min, respectively). Recoveries of mezlocillin, ampicillin, and carbenicillin from urine over 6-h periods after drug dosage were 45, 61, and 80%, respectively. A further study in 11 cancer patients examined serum maintenance levels of mezlocillin when 3-g doses were given intravenously every 4 h for at least 7 consecutive days. After 3 days of therapy, the mean serum concentrations were maintained above 50 mug/ml. Although therapeutic efficacy was not an objective of this study, all of three documented bacterial infections were cured, and no serious toxicity was encountered.

Adolescent↗
PubMed1978

Combination chemoimmunotherapy for extensive non-oat cell lung cancer.

In a prospective randomized trial, sc Corynebacterium parvum (C. parvum) immunotherapy did not significantly affect the responses and survival of 49 non-oat cell lung cancer patients receiving isophosphamide and adriamycin chemotherapy. Remissions (tumor regression greater than 50%) were seen in five of 23 patients receiving an intensive C. parvum schedule and in three of 26 patients receiving a nonintensive C. parvum schedule (22% versus 12%). Median survival was 20 weeks for patients given intensive C. parvum and 23 weeks for patients given nonintensive C. parvum. This study did demonstrate the importance of pretherapy immunocompetence, performance status, and weight loss as predictors for survival. Weight loss was the most significant prognostic factor. Performance status was closely associated with weight loss but skin reactivity to dermatophytin predicted independently and was the second most important prognostic characteristic.

Adenocarcinoma↗