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Biomedical subjects

L H Baker

Publications and source records attributed to L H Baker.

At least 91 records · Page 5Linked to original sources
PubMed1985

Epidemiological findings in a brain-tumor cluster in western Missouri.

A cluster of seven primary brain neoplasms was identified in a town of 3000 population during the 10-year period from 1973 to 1982. With six deaths, this represents an age-adjusted mortality rate 4.1 times greater than expected. No other neoplasms were found to be in excess of the anticipated incidence in this town. When brain-tumor mortality rates in 36 other towns of approximately the same population were calculated, only one other town was found to have an excessive rate. All seven tumors in this study were histologically verified: six were diagnosed as glioblastoma multiforme. Interviews were conducted with patients or next-of-kin to obtain the exposure histories of the patients. A number of respondents reported occupational or residential exposure either to a shoe factory or to one of the several chicken hatcheries in the town. Many of the patients ate fish from local ponds that had previously been used as coal mining strip pits. Two patients were siblings. None of the patients had a history of significant head trauma. This unique situation may provide an opportunity to learn more about environmental risk factors for brain neoplasia. Further epidemiological studies are planned.

Adult↗
PubMed1985

Treatment of non-small cell bronchogenic carcinoma with vinblastine and mitomycin: a Southwest Oncology Group Study.

Forty-five patients with stage III M1 non-small cell bronchogenic carcinoma were treated with vinblastine (1 mg/m2 by iv bolus twice a day on 2 consecutive days) plus mitomycin (10 mg/m2 on Day 1). This treatment was repeated at 3-week intervals for three courses. Consolidation therapy with doxorubicin and cisplatin at doses of 50 mg/m2 each was administered to responders every 4 weeks for two courses, with subsequent vinblastine and mitomycin maintenance therapy every 6 weeks. Eleven partial remissions (24%) were achieved, with a median duration of remission of 16 weeks (range, 8-32) and a median survival of 19 weeks. No differences were seen in median duration of remission or survival by cell type or performance status.

Adenocarcinoma↗
PubMed1984

Response of chronic myelogenous leukemia patients to COAP-splenectomy. A Southwest Oncology Group study.

Eighty-seven patients from 18 institutions with a confirmed diagnosis of chronic myelogenous leukemia were registered on a Southwest Oncology Group protocol for multiagent induction and single-agent maintenance chemotherapy, with randomization to an immunotherapy arm. Elective surgical splenectomy was performed for 42 patients at the completion of 3 months of induction therapy. Final analysis of the study revealed statistically significant survival advantages were correlated with age, splenectomy, the absence of hepatic leukemic infiltrate at the time of splenectomy, and race.

Adolescent↗
PubMed1984

High-performance liquid chromatographic determination of nafazatrom in human plasma using fluorescence detection.

A rapid, sensitive, and selective high-performance liquid chromatographic assay was developed for determination of the pyrazole derivative nafazatrom (Bay g 6575, NFZ) in human plasma. Separation was obtained using a normal-phase Si-60 column and a mobile phase of methylene chloride--methanol (90:10, v/v) containing 0.25% water. The fluorescence of NFZ was monitored at excitation and emission wavelengths of 232 and 362 nm, respectively. The recovery of NFZ extracted from plasma with methylene chloride was 109 +/- 5% (mean +/- S.D.) in the concentration range from 5.0 to 500 ng/ml. The assay was applied to the determination of plasma concentrations of NFZ following administration of the compound to patients in a Phase I clinical trial.

Chromatography, High Pressure Liquid↗
PubMed1984

Phase I and pharmacologic evaluation of nafazatrom in patients with cancer.

Nafazatrom was evaluated in escalating daily oral doses ranging from 0.25 to 8.0 g/m2 without producing significant toxicities. Malabsorption proved dose limiting at 8.0 g/m2 as a single daily dose, but splitting the same total dose into two or four doses circumvented this problem. Doses of 2.0 g/m2 at 6-h intervals or 4.0 g/m2 every 12 h are reasonable for Phase II and adjuvant trials. Pharmacologic evaluation of nafazatrom confirmed malabsorption at the highest single daily dose level tested and suggests that absorption was impaired in patients with extensive liver metastases.

Adult↗
PubMed1984

Clinical pharmacokinetics of high-dose mitomycin C.

The pharmacokinetic profile of high-dose mitomycin C was determined in blood plasma and urine of twelve patients with advanced malignancies in a program including autologous bone marrow transplantation. A total dose of 60 mg/m2 was given, either as a single 60-min infusion or divided into infusions of 30 mg/m2 on each of 2 days or 15 mg/m2 on each of 4 days. One group was given 15-min infusions. Samples of blood plasma and urine were analyzed by high-performance liquid chromatography. Drug concentrations in plasma followed a biphasic pattern, with a terminal elimination half-life of 45 min. This half-life value and other parameters were unaffected by dose level, infusion time, and repeated doses. The lower peak plasma concentrations following 30 mg/m2 given as 60-min infusions compared to the same dose given over 15 min may have accounted for a dramatic drop in the incidence of a severe hemorrhagic colitis. Mitomycin C was excreted in urine at about the same rate as it was eliminated from plasma, but a larger percentage of the dose appeared in urine after 15-min infusions than after 60-min infusions. The pharmacokinetic profile, together with clinical observations, suggests that the dose-limiting toxicity of mitomycin C may be related to peak drug levels, and that both these levels and the toxicity are lessened as the infusion time is increased.

Animals↗
PubMed1984

Phase II clinical evaluation of AZQ in adenocarcinoma of the lung.

Twenty patients with advanced measurable adenocarcinoma of the lung were treated with AZQ 20 mg/m2 weekly for 4 weeks, followed by a 2-week rest. No complete or partial responses were observed. Stabilization was observed in seven individuals, lasting 6-32+ weeks, with a median of 6 weeks. Toxicity was limited to reversible myelosuppression. We conclude that AZQ administered at this dose and schedule has no significant activity against advanced adenocarcinoma of the lung.

Adenocarcinoma↗
PubMed1984

Vindesine in patients with metastatic malignant melanoma: a Southwest Oncology Group study.

A phase II study using vindesine (3 mg/m2 by slow intravenous push at seven to 14 day intervals) was carried out in 42 patients with metastatic melanoma. There was one complete remission (2.5%) of greater than 12 months duration; seven partial remissions (17.5%) of two, three, three, four, five, six and eight months duration; 11 with no change (27.5%) of one to 10 months duration; and 21 (52.5%) patients with increasing disease. Toxicity included neutropenia, neurotoxicity, phlebitis and cellulitis at the site of injection, alopecia, fever and chills, myalgias, and gastrointestinal toxicity. It was concluded that vindesine does have activity in some patients with metastatic malignant melanoma. Further studies in previously untreated patients are warranted.

Adult↗
PubMed1983

Treatment of six cases of mesothelioma with doxorubicin and cisplatin.

Six patients with unresectable malignant mesothelioma were treated with chemotherapy consisting of doxorubicin and cisplatin every 3 weeks. One patient with paratesticular mesothelioma metastatic to lungs entered complete remission for 8 months; his disease has relapsed but he is alive 32 months after initiation of chemotherapy. One patient with peritoneal mesothelioma achieved partial response for 12 months. Two patients with pleural mesothelioma achieved a partial response of 5- and 6-month durations, respectively. Two patients with pleural mesothelioma failed to respond to this regimen. Thus, four of six patients responded to doxorubicin-cisplatin chemotherapy. These preliminary results merit further study and confirmation; future investigations of cisplatin alone are necessary to better define the role of this agent in mesothelioma.

Adult↗
PubMed1983

Phase I trial of aclacinomycin-A. A clinical and pharmacokinetic study.

Aclacinomycin-A is a new anthracycline antibiotic with a broad spectrum of antitumor activity in animals. Compared to doxorubicin, it was found to produce less cardiotoxicity and alopecia. A Phase I trial of aclacinomycin-A given as a weekly 15 min IV infusion was conducted in 20 previously treated patients with advanced solid tumors. Four dose levels ranging from 40 to 100 mg/m2 were studied; myelotoxicity was dose-limiting at 85 and 100 mg/m2. Other toxicities were moderate to severe nausea and vomiting in 9 patients, mild phlebitis in 2 patients, and mild abnormality of liver function tests in 3 patients. No cardiac or renal toxicities were seen, but two partial responses were observed. The pharmacokinetic profile of aclacinomycin-A in plasma and urine was studied in 3 patients given 65 mg/m2 using a high performance liquid chromatography assay. The data obtained were consistent with a two compartment model of drug disposition with initial and terminal half-life values of 6.6 min and 13.3 h, respectively. The major fluorescent metabolite was eliminated with a terminal half-life of 25 h. Two metabolites as well as the parent drug were excreted in the urine as less than 10% of the doses given. This pharmacokinetic profile is similar to that of other anthracyclines, although aclacinomycin-A appears to have lower blood levels than doxorubicin given at equivalent doses. On this weekly schedule, the recommended dose is 65 mg/m2 for Phase II trials.

Aclarubicin↗
PubMed1983

Phase II evaluation of rubidazone (NSC-164011) in advanced carcinoma of the breast. A Southwest Oncology Group study.

The SWOG carried out a Phase II evaluation of rubidazone in patients with advanced breast cancer. Good risk patients were given rubidazone 150 mg/m2 IV every three weeks. Poor risk patients were given a 25% dose reduction at the start of treatment. Rubidazone dose was increased or decreased depending on toxicity. One patient went into complete remission, four had partial remission and nine had stable disease. Forty-two patients showed increased disease on treatment. No cardiotoxicity was seen, but other common toxicities noted included mostly mild to moderate myelosuppression, nausea, vomiting and alopecia. This study failed to indicate significant antitumor activity of rubidazone in patients with advanced breast carcinoma.

Aged↗
PubMed1983

Combination chemotherapy with mitomycin C, adriamycin, and cyclophosphamide (MAC) in stage III and IV ovarian cancer.

Twenty-nine patients with stages III and IV epithelial carcinomas of the ovary were treated with a combination of mitomycin-C, adriamycin, and cyclophosphamide (MAC). A 62% response rate (CR + PR) was observed in previously untreated patients with a median survival of responding patients of 100+ weeks, compared to 29 weeks for nonresponding patients (p less than 0.001). Toxicity was acceptable with moderate to severe but manageable myelosuppression. Prospective, randomized trials comparing this drug combination to others with demonstrated efficacy are indicated.

Cyclophosphamide↗
PubMed1983

Phase I evaluation and pharmacokinetics of aziridinylbenzoquinone using a weekly intravenous schedule.

Quinone derivatives have shown intensive antitumor activity in a broad variety of neoplasias. Aziridinylbenzoquinone is designed to have adequate lipid solubility to attain useful drug concentrations in the central nervous system. A Phase I study of aziridinylbenzoquinone was conducted in 32 patients with advanced solid cancers. The drug was given as a slow i.v. injection on Days 1, 8, 15, and 22 of a 42-day cycle with a 2-week rest. Five dose levels ranging from 5 to 20 mg/sq m were studied, with 3 to 10 patients treated at each level; a total of 156 doses were administered. The major toxicity was myelosuppression with the median nadir in platelet and white blood cells occurring at Days 15 to 27 of the cycle, and first appearing at doses greater than 10 mg/sq m. Anemia was first seen at the 10-mg/sq m dose level, occurring between Days 22 and 40. Nonmyelosuppressive toxic effects included nausea and vomiting, anorexia, diarrhea, stomatitis, slight alopecia, and transient fever. The highest tolerated dose was 20 mg/sq m, the recommended dose for Phase II studies. Plasma and urine pharmacokinetics were studied in 17 patients by a high-pressure liquid chromatography method. Plasma decay curves could be fitted to a two-compartment open-system model with an overall average alpha and beta half-life values of 10.5 +/- 6.28 min and 16.90 +/- 8.63 (S.D.) hr. Aziridinylbenzoquinone levels were determined in urine samples of 12 patients, but less than 0.1% of the dose was excreted in the 0- to 4-hr sample of two patients, and none was detected in the urine of 10 patients.

Antineoplastic Agents↗