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J D Cowan

Publications and source records attributed to J D Cowan.

At least 19 recordsLinked to original sources
PubMed1991

Randomized trial of doxorubicin, bisantrene, and mitoxantrone in advanced breast cancer: a Southwest Oncology Group study.

Four hundred eleven women with metastatic breast cancer were randomly assigned to receive either 60 mg/m2 doxorubicin (130 patients), 320 mg/m2 bisantrene (146 patients), or 14 mg/m2 mitoxantrone (135 patients). The doses were given intravenously every 3 weeks with a cross-over design to determine their relative efficacy and toxicity. To be eligible, patients must have had one previous chemotherapy regimen, and patients who were estrogen receptor positive must have failed endocrine therapy. There were 365 patients assessable for response and 399 assessable for toxic effects. The median age was 57 years; 18% were premenopausal or perimenopausal. Visceral dominant disease was present in 66% of the patients. Ninety-seven percent of the patients had a disease-free interval from diagnosis to first recurrence of less than 1 year. The response rate was 28% with doxorubicin, 13% with bisantrene, and 14% with mitoxantrone (P = .004). Median time to treatment failure was 133 days with doxorubicin, 66 days with bisantrene, and 68 days with mitoxantrone (logrank P = .06). The median survival was 315 days for doxorubicin, 290 days for bisantrene, and 177 days for mitoxantrone (logrank P = .04), although survival at 2 years was similar for all three agents. There were five responses in the 66 patients crossed over to doxorubicin and one response each for patients crossed over to bisantrene (39 patients) or mitoxantrone (63 patients). Toxicity leading to discontinuance of therapy was more common with doxorubicin, and discontinuance of therapy was due primarily to patient's request or cardiotoxicity. The major dose-limiting toxic effect for all three agents was leukopenia. Nausea and vomiting, mucositis, and alopecia were more severe with doxorubicin. Congestive heart failure developed in nine patients treated with doxorubicin, zero patients treated with bisantrene, and two patients treated with mitoxantrone. A decrease in the left ventricular ejection fraction, as defined by moderate to severe Alexander grade changes, was more common in patients treated with doxorubicin (doxorubicin-treated patients = 20%, bisantrene-treated patients = 5%, and mitoxantrone-treated patients = 10%). This study demonstrates that bisantrene and mitoxantrone have only modest activity in metastatic breast carcinoma. The activity of doxorubicin is greater than that of the other two agents, but at a cost of increased toxicity.

Adenocarcinoma↗
PubMed1988

Neural nets.

Explore the source record for details and available documents.

Animals↗
PubMed1987

Phase II evaluation of bisantrene hydrochloride in refractory malignant melanoma. A Southwest Oncology Group Study.

Patients with a pathologically proven diagnosis of malignant melanoma were entered into a phase II trial of bisantrene. Eligibility criteria included: measurable, metastatic disease; performance status 0-2 SWOG; and adriamycin total cumulative dose of less than 400 mg/m2. The initial bisantrene dosing schedule was 260 mg/m2 every three weeks for good risk patients. Due to the absence of an objective response and the lack of severe toxicity in the first 25 bisantrene treated patients, the starting dose was increased to 300 mg/m2 for good risk patients. Fifty-one patients received a median of two bisantrene courses (range 1-11 courses). Leukopenia was the major toxicity. Fifteen (68%) of the 22 good risk, intermediate dose patients (260 mg/m2), and 8 (80%) of the 10 good risk, high dose patients (300 mg/m2) evaluable for toxicity experienced mild-severe leukopenia. None of the 51 patients experienced a complete or partial response to bisantrene. Median survival was 3.3 months. We conclude that bisantrene is ineffective in the treatment of metastatic melanoma.

Adult↗
PubMed1986

Simultaneous in vitro drug sensitivity testing on tumors from different sites in the same patient.

A human tumor cloning assay was used to analyze drug sensitivity profiles for 99 pairs of tumor samples taken simultaneously from the same patient. These pairs included two areas of the same primary (12 pairs), primary tumor versus metastasis (29 pairs), and metastasis versus metastasis (45 pairs). In addition, to assess variability in the culture and sensitivity techniques, 13 specimens were divided equally and processed twice. One hundred fourteen evaluable drug sensitivity tests were performed on the specimen pairs. Drug sensitivity profiles for the same specimen processed twice demonstrated good agreement (P = 0.03). Sensitivity profiles from two different areas of the same primary were also quite similar (P = 0.002). However, when one sampled a primary tumor and its metastasis for drug sensitivity testing, the agreement (in terms of percent survival) was poor (P = 0.84). Agreement was also poor for drug sensitivity profiles of one metastasis versus another metastasis (P = 0.39). This heterogeneity in drug sensitivity profiles of primary versus metastasis and of metastasis versus metastasis could account for some of the false positives and false negatives noted in clinical correlation trials with the cloning assay. It may also have implications for adjuvant treatment programs where chemosensitivity of the primary tumor can be determined, but will probably not be predictive for chemosensitivity of the micrometastases.

Antineoplastic Agents↗
PubMed1986

A phase II study of bisantrene in malignant lymphomas. A Southwest Oncology Group Study.

Forty evaluable patients with malignant lymphoma (ML) were treated with bisantrene at a dose of 260 mg/m2 every 3 weeks (18 patients) or 208 mg/m2 every 3 weeks (22 patients). The initial dose rate was determined on the basis of expected myelosuppression. Patients were heavily pretreated and had advanced disease (92% had stage IV). The overall response rate was 10% and included 1 partial response (PR) in 17 patients with Hodgkin's disease (HD), 1 PR and 1 complete response (CR) in 5 patients with favorable histology in non-Hodgkin's lymphoma (NHL), and 1 PR in 18 patients with unfavorable histology in NHL. Neutropenia (WBC less than or equal to 3000 cells/microliter) was the most common toxicity, occurring in 50% of patients. Phlebitis was a common side effect in patients treated with bisantrene administered by way of peripheral veins. Bisantrene has limited activity in heavily pretreated patients with HD or unfavorable histology in NHL. The role of bisantrene for treatment of NHL with favorable histology or for treatment at an earlier point in the natural history of ML is unknown.

Anthracenes↗
PubMed1986

Direct effects of the hypoxic cell sensitizer misonidazole on colony formation in a human tumor cloning assay.

The human tumor cloning assay as described by Hamburger and Salmon was utilized to study the direct antitumor effects of the hypoxic cell sensitizer misonidazole (MISO). Cells from 106 tumor specimens directly obtained from patients were exposed to MISO at clinically achievable drug concentrations (0.5 mM). Of 30 evaluable tumors, seven specimens (23%) showed a less than or equal to 50% decrease of TCFU's. In vitro sensitivity to MISO was noted in human breast cancer, renal cancer, non small-cell lung cancer, and adenocarcinoma of unknown primary site. A dose response relationship was demonstrated in a subset of experiments including 6 patient's tumors and one human breast cancer cell-line. An analysis relating MISO sensitivity or resistance to the results obtained with other, simultaneously tested standard anticancer drugs indicated that tumors exhibiting a less than or equal to 50% decrease of TCFU's in the presence of MISO were also likely to be sensitive to other cytotoxic drugs. In summary, our data suggest that the 'nitroimidazoles' may exert clinically significant direct antitumor effects in individual tumors. The human tumor cloning assay may have potential to evaluate these direct effects of MISO-analogues and other new radiosensitizers currently being tested in clinical trials.

Antineoplastic Agents↗
PubMed1985

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↗
PubMed1979

Temporal oscillations in neuronal nets.

A model for the interactions of cortical neurons is derived and analyzed. It is shown that small amplitude spatially inhomogeneous standing oscillations can bifurcate from the rest state. In a periodic domain, traveling wave trains exist. Stability of these patterns is discussed in terms of biological parameters. Homoclinic and heteroclinic orbits are demonstrated for the space-clamped system.

Brain↗
PubMed1979

A mathematical theory of visual hallucination patterns.

Neuronal activity in a two-dimensional net is analyzed in the neighborhood of an instability. Bifurcation theory and group theory are used to demonstrate the existence of a variety of doubly-periodic patterns, hexagons, rolls, etc., as solutions to the field equations for the net activity. It is suggested that these simple geometric patterns are the cortical concomitants of the "form constants" seen during visual hallucinosis.

Action Potentials↗
PubMed1979

Further evidence for four mechanisms mediating vision at threshold: sensitivities to complex gratings and aperiodic stimuli.

It is now generally accepted that several mechanisms mediate contrast detection at threshold. Many attempts to measure the bandwidths of these mechanisms using subthreshold summation have yielded estimates suggesting very narrow frequency tuning. We have measured thresholds for three classes of stimuli: gratings containing two sinusoidal components, sums of "difference of Gaussian" (DOG) patterns, and square waves. The results of the subthreshold summation experiments with gratings are consistent with those of other studies. All of these thresholds can be predicted by a model requiring only four center-surround-type mechanisms at each retinal locus. These mechanisms have a full bandwidth at a half-height of about 1.75 octaves. Quantitative prediction of sensitivities depends critically upon spatial probability summation. It is this spatial nonlinearity that yields these somewhat conterintuitive results. The much narrower bandwidths inferred by others are due to the assumption of linearity used in their analyses.

Computers↗
PubMed1975

Osteomyelitis in children: comparison of hematogenous and secondary osteomyelitis.

SUMMARY: A review of osteomyelitis in 54 patients treated at the Dr. Charles A. Janeway Child Health Centre over a 4-year period revealed equal frequencies of secondary and hematogenous osteomyelitis. Although the clinical picture in patients with hematogenous osteomyelitis was classic, patients with secondary osteomyelitis presented with an altered clinical response. Patients with secondary osteomyelitis have a history of an antecedent puncture wound or an inadequately treated contiguous focus of infection; antistaphylococcal antimicrobial therapy was ineffective for most because gram-negative bacilli were isolated in this group of patients. In contrast to patients with hematogenous osteomyelitis, who frequently respond to intensive antimicrobial therapy, those with secondary osteomyelitis will frequently require surgical intervention to eradicate the infection.

Abscess↗