Toxicity of single- vs. fractionated-dose ifosfamide in non-small cell lung cancer: a multi-center study.
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Biomedical subjects
Publications and source records attributed to L R Morgan.
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This study tested the feasibility of using oral ifosfamide to treat bronchogenic carcinoma and compared the pharmacokinetics of intravenous and oral doses of the drug. Patients with advanced bronchogenic carcinoma were evaluated for toxicities associated with oral ifosfamide therapy. Pharmacokinetics for various oral and intravenous doses of ifosfamide were determined by a gas-liquid chromatographic assay of plasma and urine samples. Toxicities associated with oral ifosfamide therapy were minimal. Calculated pharmacokinetics parameters are listed, with the half-lives varying from 0.5 to 4.6 h. Oral ifosfamide therapy was determined to be feasible, and further studies are justified to assess the pharmacokinetics of the optimum dosage and scheduling regimens.
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To see whether urine enzyme activities could be used as an index in evaluating the disease status of leukemia patients, we examined the activities of four enzymes: arylsulfatases A(AS-A) and B(AS-B), alkaline phosphatase (AP), and lactate dehydrogenase (LDH). AP and LDH showed no consistent patterns. The activities of AS-A and AS-B correlated well with the patient's clinical status, increasing during progression of disease and decreasing toward normal activities during responses to therapy, as judged from bone marrow cellularity and differential. Among 23 untreated patients with a histologic diagnosis of acute leukemia we found increased activities of the urine enzymes in these proportions: AS-A in 23 patients (100%), AS-B in 22 (95.7%), AP in 7 (30.4%), and LDH in 10 (43.5%). Five patients in remission from acute leukemia had normal activities for all four enzymes. In one patient in remission for more than one year, a rise in urinary arylsulfatase activity preceded observable bone marrow relapse by 4 months. Unlike that of serum of urine lysozyme and serum copper, the determination of urine arylsulfatase activities appears to be a consistent, useful indicator of response to antileukemic therapy. In contrast to the determination of polyamines, the quantitation of arylsulfatase activity is achieved with greater ease and with instrumentation available in most clinical laboratories.
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5-Flourouracil (5-FU) and methyl-CCNU have demonstrated separate sensitivities in carcinoma of the large bowel. This study was an attempt to see if methyl-CCNU versus methyl-CCNU plus 5-FU would demonstrate different responses in advanced colorectal carcinoma. Forty-nine patients have been evaluated, 14 receiving methyl-CCNU and 35 receiving 5-FU plus methyl-CCNU. One partial response has been seen with methyl-CCNU alone in a patient with liver metastasis. Thirteen partial responses have been noted in patients treated with the two-drug combination. There was a significant difference in the median survival of the responders versus the nonresponders for the two-drug group. Side effects were expected: nausea and vomiting, leukopenia, and thrombocytopenia. Plasma carcinoembryonic antigen and urine arylsulfatase were measured in all patients and correlated well with response.
Tamoxifen (NSC-180973; ICI-46474) can provide palliation to patients with advanced breast cancer whose tumors contain estrogen-binding proteins (EBP). The drug is most effective in patients with bone metastasis and minimal prior therapy. In the present study, 72 patients with advanced breast cancer were evaluated for their response to oral tamoxifen therapy administered at a dose of 20 mg twice daily. Twenty-eight of 72 patients (38%) demonstrated objective responses to tamoxifen therapy. For patients with a positive EBP and no prior chemotherapy, eight of 11 (74%) responded. No patient possessing a tumor negative for EBP achieved a remission. Patients with tumors that possessed normal arylsulfatase B and glucose-6-phosphate dehydrogenase enzyme activities responded most favorably to tamoxifen therapy. These results demonstrate that tamoxifen is effective in the treatment of patients with advanced breast cancer, and EBP and specific enzymes might be useful in selecting the patients for hormone manipulation.
Arylsulfatase B activity has been determined in 24-hour urine samples from 243 patients with colorectal cancer. Elevated activity of the enzyme was obsereved in 172 out of 243 (71%) patients. Employing Dukes' modified classification of colorectal cancer, urine arylsulfatase B activity was elevated in Dukes' A lesions-1/8 (12%), Dukes' B lesions-24/43 (55%). Dukes' C lesions-89/111 (80%), and Dukes' D lesions-66/81 (82%). Arylsulfatase B activity in urine, when elevated, may be used to follow response to therapy since in those patients with elevated urine arylsulfatase B values who subsequently responded to therapy, the enzyme values became or approached normal. Urine arylsulfatase B activity also correlated with plasma carcinoembryonal antigen (CEA) as a diagnostic indicator of colorectal cancer in 33/46 (71%) patients. In contrast to the urinary findings, arylsulfatase B activity in tumor tissue was elevated in only 24% (27/110) of the specimens of colorectal cancer. It was also found that in a group of 55 patients treated with 5-fluorouracil, all of the 13 patients that showed objective response to therapy had activities of arylsulfatase B in the tumor tissue within the normal range for large bowel mucosa. Nevertheless, 22 to 26 of the 43 patients that did not respond also presented values in the normal range. The roles of lysosomal enzymes in colorectal cancer are discussed.
At the present time several techniques of bone grafting for restoration of mandibular defects are being employed. These methods are well established by clinical trials and animal research. Other methods are in the experimental stage. Regardless of the technique utilized it remains paramount that the surgeon plan the initial procedure with great care as each failure results in diminished blood supply to the graft bed and makes subsequent procedures less likely to succeed. The well known principles of bone grafting involve establishing good nutritional status of the patient, proper preparation of the graft bed by insuring adequate soft tissue and adequate blood supply, elimination of infection from the graft bed, provision of adequate fixation and immobilization of the graft, and careful closure of soft tissues to prevent hematoma formation. These principles remain inviolable if the procedure is to succeed.
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