Phase II trial of bisantrene in previously treated patients with ovarian carcinoma: a Southwest Oncology Group Study.
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Adult↗
Biomedical subjects
J D Cowan
Publications and source records attributed to J D Cowan.
A randomized trial of doxorubicin, mitoxantrone and bisantrene in advanced breast cancer (a South West Oncology Group Study).
New agents with increased activity and/or reduced toxicity are needed for the treatment of advanced breast cancer. The anthracene derivatives mitoxantrone and bisantrene had significant activity and acceptable toxicity in phase II trials. In an ongoing phase III trial we have now randomized 150 patients with advanced breast cancer to either doxorubicin (60 mg/m2), mitoxantrone (14 mg/m2) or bisantrene (260 mg/m2) i.v. q 3 weeks with re-randomization for cross-over at the time of progression to determine the relative efficacy and toxicity of these three agents. To be eligible, patients must have had only one previous chemotherapy regimen. ER positive patients must have failed endocrine therapy. Patients with CHF or severe cardiac disease were ineligible. In this preliminary evaluation, 117 patients are evaluable for response and 110 for toxicity. Median age for all patients is 58 years (range 26-78). The majority (86%) are postmenopausal. Fifty-nine percent percent of the patients have visceral dominant disease. Estrogen receptor is positive in 37%, negative in 39% and unknown in 24% of patients. Median performance status (SWOG) is 1, range 0-2. Objective responses have been observed on each arm (doxorubicin 9/35, mitoxantrone 6/38, bisantrene 6/44). Thirty-two patients are evaluable for cross-over response (doxorubicin 2/13, mitoxantrone 1/11, bisantrene 0/8). The predominant toxicity is leukopenia with a nadir WBC count less than 2000 in 45% of all courses administered. Leukopenia is similar with the three drugs. Significant nausea, vomiting and alopecia are common with doxorubicin and uncommon with the other agents. Congestive heart failure has been observed in one patient (doxorubicin). Definitive conclusions regarding the efficacy and toxicity of these agents await the completion of this trial.
Adult↗
Predictive value of trypan blue exclusion viability measurements for colony formation in a human tumor cloning assay.
Specimens (173) were evaluated to assess the predictive value of cell viability as measured by Trypan Blue exclusion on colony formation in a human tumor cloning system. Overall, there was no significant correlation between Trypan Blue exclusion-determined viability and colony formation in soft agar for these specimens (p = 0.43). This lack of significant correlation was maintained for primary, metastatic, solid, and fluid tumor specimens. These data suggest that, in this soft agar system, specimens containing cells with low Trypan Blue exclusion viability should not be excluded from testing, and that it may not be advantageous to plate on the basis of "viable cells" as measured by Trypan Blue exclusion.
Cell Survival↗
Addison's disease due to metastatic carcinoma.
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Addison Disease↗
Bisantrene, an active drug in patients with advanced breast cancer.
We have previously reported that bisantrene has significant activity against a variety of tumors in the human tumor soft agar cloning assay. An update of that experience reveals that 26% of evaluable human breast cancer specimens were sensitive to bisantrene, which had activity equivalent or superior to that of doxorubicin. Because of the preclinical activity of bisantrene and its activity in the cloning assay, bisantrene was studied in a phase II clinical trial of 30 patients with advanced breast cancer refractory to standard agents. Six patients (20%) had objective complete or partial regressions, including one patient with complete regression of lymphangitic lung metastases lasting greater than 18 months, confirming the antitumor activity of this compound. Two of the six responding patients had failed doxorubicin treatment, implying a lack of complete cross-resistance. Bisantrene toxicity was acceptable in most patients, with reversible myelosuppression being the most frequent side effect. Phase III trials of this promising new agent are warranted.
Adult↗
Use of a human tumor cloning system to screen retinoids for antineoplastic activity.
Retinoid analogs are being actively evaluated as antitumor agents in man. A human tumor cloning system was used to assess the antineoplastic activity of all-trans-retinoic acid, all-trans-retinol and 13-cis-retinoic acid. The effect of retinoids on the formation of tumor colony forming units (T-CFU) was surveyed for 67 different human tumors. These analogs showed minor activity in a variety of neoplasms. The decrease in T-CFU varied between histologic tumor types and between tumor of the same type. No significant difference between retinoid analogs was noted.
Antineoplastic Agents↗
Comparative cytotoxicity of adriamycin, mitoxantrone and bisantrene as measured by a human tumor cloning system.
A human tumor cloning system was used to assess the cytotoxicity of adriamycin, mitoxantrone and bisantrene at concentrations that are equitoxic in man. There were 989 specimens evaluable for drug sensitivity analysis. Overall, adriamycin showed in vitro cytotoxicity (greater than or equal to 50% decrease in tumor colony forming units) 14% of the time; mitoxantrone, 21% of the time; and bisantrene, 31% of the time. Three hundred ninety-nine of these evaluable specimens were simultaneously tested against more than one of the agents, providing 631 two-way drug comparisons. For these comparisons, there was lack of co-resistance 27-34% of the time, with mitoxantrone being more active than adriamycin (p less than .05) and bisantrene being more active than adriamycin (p less than .01) or mitoxantrone (p less than .01). These data suggest that comparative and sequential clinical use of these agents should be investigated.
Anthracenes↗
The effects of the ionophore A23187 on pattern formation in the alga Micrasterias.
We have used the divalent cation ionophore A23187 to investigate the hypothesis that cytoplasmic localization of Ca2+ is responsible for localized growth in the alga Micrasterias. In a preliminary study we found that, of the major salts contained in the cell's medium, only CaCl2 was needed for normal development. In cells developing in the presence of A23187 and extracellular Ca2+, we postulated that the ionophore would induce a spatially uniform influx of Ca2+ that would overwhelm endogenous Ca2+ gradients. When developing cells were treated with A23187 and 2 mM CaCl2, we observed a delocalization of the cell's normal pattern of wall deposition. This effect was less pronounced when cells were exposed to A23187 and 2 mM MgCl2. These results support the hypothesis that localized regions of high Ca2+ concentration normally mediate localized expansion of tip-growing lobes in Micrasterias.
Anti-Bacterial Agents↗
Testing the escape hypotheses. Alcohol helps users to forget their feelings.
Several hypotheses suggest that alcohol is often used to "escape"--to forget unpleasant feelings resulting from personal problems or social stresses. To test alcohol's effects on memory for feelings, 1.1 ml/kg of alcohol (A) or placebo (P) was given in two sessions, 48 hours apart, to 32 subjects divided into four equal drug groups (P-P, P-A, A-P, A-A). The subjects filled out the Profile on Mood States (POMS) after drug ingestion in session 1 while experiencing and learning these emotions. Their memories were tested when they tried to replicate these POMS ratings after drug ingestion in session 2. Alcohol given before memory testing decreased accuracy on each of the six POMS scales, especially Fatigue. However, alcohol did not impair memory for previously learned verbal and pictorial stimuli, and it produced no measurable changes in current feelings. These findings indicate that the impairment of memory for feelings may be a newly discovered specific pharmacological effect of alcohol.
Adult↗
Outline of a theory for the ontogenesis of iso-orientation domains in visual cortex.
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Afferent Pathways↗
Localized effects of spatial frequency adaptation.
The spatially localized threshold-elevation aftereffect of spatial-frequency adaptation was measured by using localized, aperiodic test patterns that have bandpass Fourier transforms. At a given retinal location, the threshold-elevation curves are consistent with the fatigue of size-turned mechanisms with center-surround sensitivity profile. Only a few different sizes of such mechanisms were required to fit the local results. The local aftereffect was also measured as a function of eccentricity near the fovea. The results indicate that the threshold-elevation aftereffect of spatial-frequency adaptation is not spatially homogeneous.
Adaptation, Ocular↗
Intrahepatic artery 5-fluorouracil and mitomycin-C in previously untreated patients with hepatic metastases from colorectal carcinoma.
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Adult↗
Phase II trial of mitoxantrone in previously untreated patients with colorectal adenocarcinoma: A Southwest Oncology Group Study.
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Adenocarcinoma↗
Detection of recurrent breast cancer.
Most clinicians attempt to identify and treat recurrent breast cancer at the earliest sign of relapse. In an effort to better define the usefulness of commonly used clinical and laboratory tools in evaluating patients after mastectomy, we retrospectively analyzed 120 cases and reviewed the literature. One hundred fifteen sites of metastatic disease were identified in 55 patients, with bone, lung, liver, and skin most common. History and physical examination disclosed 66% of these metastatic events. Of 36 patients with probable bone involvement, 15 were identified by bone scan while asymptomatic. Of 31 patients with evidence of pulmonary metastases, 12 were entirely asymptomatic when identified with a screening chest roentgenogram. In contrast, 36 of 45 hepatic, cutaneous, lymphatic, central nervous system, and ocular metastases were suggested by purely clinical findings. We conclude that basic clinical skills (ie, history-taking and physical examination) are two most important means by which we identify patients with recurrent breast cancer. While chest roentgenogram and bone scan may uncover metastases in asymptomatic patients, liver function tests and radionuclide scans of brain and liver have very low yield in patients clinically free of organ involvement.
Bone Neoplasms↗
Specificity and plasticity of retinotectal connections: a computational model.
A computational model is presented which simulates the development and regeneration of orderly connections between retinal fibers and tectal cells in frogs and goldfish. The model distinguishes two aspects of retinotectal connectivity: (1) the contact adhesion between retinal fibers and tectal cells as mediated by fixed chemospecific markers and (2) the formation of modifiable synapses between them. Chemospecificity is assumed to be an intrinsic property of both the retina and tectum and is modeled as a graded distribution of a binding determinant or marker. Synapse formation depends upon the timing of neural activity as well as on the intinsic chemospecificity of retinotectal contacts. In addition to the normal development and regeneration of the retinotectal map, the model simulates the compressed, expanded, translocated, and rotated maps that have been found in surgically manipulated contexts. There examples of plasticity in the retinotectal map can be simulated without assuming any changes in the marker distributions. Moreover, the model demonstrates that a very shallow gradient of a single marker suffices to organize retinotectal connections in a variety of contexts.
Afferent Pathways↗
Bone marrow necrosis.
Extensive bone marrow necrosis is an unusual histologic finding most commonly identified after autopsy. We describe a patient with poorly differentiated lymphocytic lymphoma who manifested pancytopenia and marrow necrosis. Bone marrow scanning with 99mTc-sulfur-minicolloid provided a noninvasive means to assess the extent of marrow damage. Our patient's condition improved clinically following cytotoxic chemotherapy demonstrating that marrow necrosis may be associated with a treatable disease.
Adult↗
An immunologic network.
The immune system is a complex network of molecules and cells specifically connected by the complementarity of receptors for antigen and receptors for receptors. The network includes multiple positive- and negative-feedback loops, which modulate the type, magnitude, and duration of responses. The great challenge is to devise ways to manipulate the system specifically to induce effective autoimmunity to cancer, to prevent allograft rejection, and to turn off undesirable responses in allergies and autoimmune diseases. Recognition of the immune system as a network helps to explain why these objectives are so difficult and why manipulation of multiple components to achieve desired regulation may be required. But presumably manipulation must be focused on connectivity between receptor for epitope and receptor for receptor to achieve a high degree of specific regulation.
Animals↗
Defeated and joyless: potential measures of change in drug abuse characteristics.
Defeated and Joyless scales were developed from a questionnaire given to 54 normal, 53 alcoholic, and 28 opiate addict subjects. The Defeated scale differentiates the alcoholics and addicts from normals but not from each other, whereas the Joyless scale differentiates addicts from both alcoholics and normals. When shown to 48 college students, a film about poverty increased the Joyless score, as well as other measures, but had little effect on the Defeated score. These scales appear to distinguish between self-concept (Defeated) and mood (Joyless) components of hypophoria, an affective disorder hypothesized to be associated with drug abuse.
Adult↗