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Biomedical subjects

L H Baker

Publications and source records attributed to L H Baker.

At least 127 records · Page 7Linked to original sources

A phase I-II study of maytansine utilizing a weekly schedule.

Maytansine, a new ansa macrolide antitumor antibiotic, was administered to a total of 107 patients in a Phase I-II study. Dose-limiting toxic reactions which occurred at 0.75-1.0 mg/M2 in both Phase I and II were neurologic and consisted primarily of lethargy/weakness (a debilitation syndrome) and paresthesias. Gastrointestinal and neurologic toxic reactions increased in frequency and severity as a function of dose. Myelosuppression, while infrequent, occurred only in previously treated patients. Changes in liver function tests were subclinical. Two partial remissions were observed at a dose-level of 0.5 mg/M2 in Phase I:1 patient with squamous cell carcinoma of the lung responded for five weeks, while the other patient with adenocarcinoma of the lung responded for four weeks. One partial remission, lasting 14 weeks was seen in Phase II in a patient with malignant melanoma treated at dose-level of 1.0 mg/M2. All responses were in heavily pretreated patients. pairs of small bowel biopsy specimen used to define the mitotic index demonstrated peak mitotic arrest at 24 hours in contrast to vinca alkaloids which appear to have a peak mitotic arrest at 12-24 hours.

Adult↗

Cyclophosphamide, vincristine, adriamycin, and DTIC (CYVADIC) combination chemotherapy for the treatment of advanced sarcomas.

One hundred and forty adult patients with advanced sarcomas (125 soft tissue and 15 bone) were treated with a combination chemotherapy regimen consisting of cyclophosphamide, vincristine, Adriamycin, and DTIC (CYVADIC). There were 21 (15%) complete and 45 (32%) partial responders, with an overall response rate of 47%. The response rate was 50% (17% complete) for patients with soft tissue sarcomas compared with 20% (none complete) for patients with bone sarcomas. The median duration of response was 9.5 months (range, 1-40+ months) for complete responders and 7 months (range, 1-31 months) for partial responders. The median time to achieve response was 9 weeks and the median number of courses of therapy to response was three. The median survival time was 16 months for responders compared with 7 months for nonresponders (P = 0.001). The most responsive tumor types were neurofibrosarcoma, rhabdomyosarcoma, leiomyosarcoma, fibrosarcoma, and angiosarcoma. Pulmonary and soft tissue metastases were more responsive than bone and liver metastases. CYVADIC toxicity was predominantly limited to myelosuppression, vomiting, fever of unknown origin, and neuropathy. CYVADIC is an effective combination chemotherapy regimen in the treatment of advanced sarcomas.

Antineoplastic Agents↗

Pharmacokinetics of 5-fluorouracil administered orally, by rapid intravenous and by slow infusion.

Pharmacokinetic studies of 5-fluorouracil (5-FUra) were performed on 18 patients divided into three groups: seven patients were given 5-FUra i.v. by rapid injection; five patients received the drug p.o.; and six patients were treated by continuous i.v. infusion for 96 hr. The results showed rapid i.v. injection to be manifested by high early levels of drug achieved both in plasma and bone marrow with a rapid fall afterwards. Administration of 5-FUra p.o. gave rise to erratic plasma values due to greater variability in absorption, whereas 96-hr i.v. infusions showed constant levels of the drug in plasma and significantly (50- to 1000-fold) less 5-FUra in bone marrow. The main difference observed between rapid injection and slow infusion in the kinetics of the drug was the very high level of 5-FUra reached by rapid injection in plasma and bone marrow, which was of short duration (min) when compared to the low sustained levels observed during infusion. This route-dependent pharmacokinetic profile is consistent with the reported absence of myelosuppression in prolonged infusion and may be related to the resultant lower levels of 5-FUra achieved in bone marrow.

Adenocarcinoma↗

Phase I-II clinical trial of gallium nitrate (NSC-15200).

Gallium nitrate (NSC-15200), a group IIIa metal salt, was evaluated in a phase I-II clinical trial, In phase I trial, exploring bolus administration of the drug at 3-week intervals, dose-limiting renal toxicity was observed at doses exceeding 700 mg/m2. Hematological toxicity was minimal. Ototoxicity was observed in one patient. A phase-II trial was initiated evaluating the drug at 700 mg/m2 given at 2- and 3-week intervals. Antitumor responses were observed in one patient with soft-tissuesarcoma and in two patients with small cell carcinoma of the lung. In two of these responders, pretreatment 67Ga scan was positive. Further clinical trials with the drug appear indicated, utilizing the every 2 week schedule. Pretreatment hydration combined with osmotic diuresis may ameliorate potential nephrotoxicity.

Adult↗

Transfer factor.

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Animals↗

Autopsy diagnosis of Legionnaires' disease in immunosuppressed patients. A paleodiagnosis using Giemsa stain (Wohlbach modification).

A diffuse pneumonia characterized by short Giemsa-stained, gram-negative rods that were not cultured was diagnosed at autopsy in the fall of 1975 in three immunosuppressed patients who had had renal transplants. An acute fibrinous exudate was found, with macrophages, neutrophils, and numerous short bacilli in each inflamed alveolus as shown by Giemsa's stain (Wohlbach modification). Transplantation was stopped for 1 month. The institutional infection control committee discussed the cases, and increased observation. After the Legionnaires' disease agent was identified in 1977, the bacteria were stained by Dieterle's method and identified as Legionnaires' disease bacteria by direct fluorescent antibody test. No further cases have been identified in the succeeding 62 renal transplantations at this medical center. Although Wohlbach's modification of Giemsa has given consistently good staining of the Legionnaires' disease bacterium in our cases, unclarified factors may interfere with good staining, and the May-Grünwald Giemsa stain was unsatisfactory.

Adult↗

Use of VM-26 as a single agent in the treatment of renal carcinoma.

VM-26 was administered to 13 patients with metastatic adenocarcinoma of the kidney. Twelve of the 13 patients were assessable. The remaining patient was nonevaluable due to early death as defined in the protocol. No responses were observed in any of the 12 patients. Nonhematological toxicity was mild except for one instance of life-threatening hypotension, occurring during the infusion of VM-26. Significant leukopenia (less than 3000/mm3) occurred in 29% of courses and significant thrombocytopenia (less than 100,000/mm3) occurred in 14% of courses. Further studies using VM-26 in renal cell carcinoma do not seem warranted.

Adenocarcinoma↗

Mitomycin-C alone and in combination with infused 5-fluorouracil to the treatment of disseminated gastrointestinal carcinomas.

One hundred and thirty-two previously untreated patients with metastatic adenocarcinoma of the gastrointestinal (GI) tract were randomized to receive either a 120-hr infusion of 5-fluorouracil (5FU) with mitomycin-C or mitomycin-C alone. Superiority of the combination treatment was demonstrated with remissions in 30 out of 82 (37%) patients versus 9 out of 50 (18%) with the single drug treatment (P = 0.02). The median survial with 5FU--mitomycin-C was 29 weeks, as opposed to 20 weeks with mitomycin-C alone (P = 0.03). The combination produced significantly more severe myelotoxicity than the single drug, and jaundiced patients experienced more myelosuppression than non-jaundiced patients with both treatments.

Adenocarcinoma↗

Measuring clinical competence of medical students.

Evidence of clinical competence for medical students entering the clinical clerkships at the University of Kansas College of Health Sciences is established by passing two different examinations: a 100 item multiple choice examination and a videotaped history and physical examination by each student of a simulated patient, being rated by that patient and two examiners. In 1976 the class of 196 medical students took an average 1.85 written examinations per student. With 70% or better constituting a passing score, 30.6% passed on the first attempt, 55.6% the second, 11.2% the third and 2.5% the fourth. Each student passed the televised practical examination and had the opportunity to review his or her videotape with a critiqued data base and the examiners' and simulated patient's evaluations in hand. Correlation coefficients for all 196 students between scores of written examinations, medicine tutors, examiners and professional patients revealed weak but significant correlations between the assessments of examiners and medical tutors and assessments of examiners and written examination scores, but not between other evaluations. This scheme of proof of competence appears to be objective and direct, and serves the convenience of both students and teaching staff.

Clinical Competence↗

Phase I--II study of intermittent bolus administration of DTIC and actinomycin D in metastatic malignant melanoma.

Twenty-six patients with disseminated malignant melanoma were treated with intermittent bolus DTIC and actinomycin D in an escalating dose schedule, starting at 650 and 1 mg/m2 respectively. Courses were repeated at 3--4-week intervals. Twenty four patients were evaluable for toxicity and 22 were evaluable for response. Two patients (9%) had a complete remission lasting 7+ and 14 months, and three patients (14%) had a partial remission lasting 2+, 5+, and 14+ months. Nausea and vomiting, lasting 24 hours, was observed in 88% of patients, while diarrhea was noted in 17%. Stomatitis and alopecia were less frequently observed. All responses occurred at nonmyelosuppressive doses and in patients with visceral-predominant metastases. This schedule offers the patient the convenience of single-day treatment and less prolonged gastrointestinal intolerance. Further evaluation of this drug combination and schedule would appear to be indicated.

Adult↗

Clinical trial of rubidazone in advanced squamous cell carcinoma of the lung and adenocarcinoma of the large intestine.

Sixteen patients with disseminated squamous cell carcinoma of the lung and 26 patients with adenocarcinoma of the colon and rectum were given rubidazone. Only one partial remission was observed in a previously untreated patient who had local recurrence of a rectal adenocarcinoma. The main toxic effects observed in previously treated patients consisted of leukopenia and thrombocytopenia. Also observed were anorexia, nausea, vomiting, alopecia, fever, and chills. Cardiotoxicity was observed in one patient after a total dose of 720 mg/m2 of rubidazone. It is concluded that rubidazone is a relatively inactive compound in the management of these two diseases.

Adenocarcinoma↗

Mitomycin C, vincristine, and bleomycin therapy for advanced cervical cancer.

The Southwest Oncology Group has treated 130 patients with advanced disseminated uterine cervical carcinoma no longer amenable to therapy with further radiation or surgery. Patients received one of three different schedules of mitomycin C, vincristine and bleomycin. A twice weekly schedule of bleomycin and vincristine produced response in 60% of patients. An infusion bleomycin schedule produced response in 39% of patients and a once weekly vincristine bleomycin schedule produced a 25% response rate (45% overall). Responding patients lived significantly longer than nonresponders (30 vs 18 weeks). Toxicities encountered included leukopenia, thrombocytopenia, peripheral neuropathy, gastrointestinal upset, dermatitis, and alopecia. We believe two of the schedules utilized represent an improvement in producing tumor remission induction in this previously recognized refractory carcinoma.

Adult↗

Dose response evaluation of adriamycin in human neoplasia.

Because patients treated with 60-90 mg/m2 every three to four weeks reach cardiotoxic doses of 550 mg/m2 within 36 weeks, prolonged treatment with Adriamycin is limited. The purpose of this study was to determine whether lower doses could be given over longer periods without loss of efficacy. Good risk patients treated with 75, 60, or 45 mg/m2 had remission rates of 25, 27, and 19%; poor risk patients treated with 50 and 25 mg/m2 had remission rates of 16 and 12% respectively. Although a dose response was identified, there were no statistically significant differences in remission rates, durations of remission, or toxicities in the dose schedules studied. Irreversible congestive heart failure occurred in five patients with cumulative doses of 240-390 mg/m2. Unless rapid remission induction is urgent, we recommend 60 mg/m2 X four doses and measurement of myocardial function if treatment is to continue.

Adult↗