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Biomedical subjects

S Cheeseman

Publications and source records attributed to S Cheeseman.

7 recordsLinked to original sources

Caelyx (stealth liposomal doxorubicin) in the treatment of advanced breast cancer.

Anthracyclines are amongst the most active drugs in the treatment of breast cancer. Stealth liposomal doxorubicin (Caelyx, Doxil, Alza Pharmaceuticals Inc.) is a promising new agent under investigation for the treatment of breast cancer and other solid tumours. The liposomal encapsulation alters drug pharmacokinetics and leads to a marked change in toxicity profile compared to non-liposomal doxorubicin. The results of recently completed and ongoing clinical trials in breast cancer are reviewed.

Antineoplastic Agents↗

Phase II study of oral topotecan in advanced non-small cell lung cancer.

This study was designed to assess the activity of oral topotecan (TPT) in patients with advanced non-small cell lung cancer previously untreated with chemotherapy. Eligible patients had inoperable stage III or stage IV non-small cell lung cancer and were chemotherapy-naive. Other inclusion criteria were Eastern Cooperative Oncology Group performance status 0, 1, or 2, adequate bone marrow, and renal and hepatic function. Of 30 patients, 29 were assessable for response. Oral TPT was administered for 5 days every 21 days for up to six cycles unless disease progression or unacceptable toxicity occurred. Patients received a dose of 2.3 mg/m2/day for the first cycle. Dose modification for subsequent cycles was based on tolerability. Patients completed symptom questionnaires every 3 weeks. Pharmacokinetics were evaluated in all patients during cycle 1. Three patients had radiological responses with a reduction in tumor size of 30-40%. No patients achieved complete or partial responses to treatment. Thirteen patients had a stable disease (43.3%), and the median survival was 39.9 weeks with a 1-year survival of 33.3%. At the time of analysis, 27 patients had died. Median time to progression was 12.3 weeks. Treatment was well tolerated. A total of 125 cycles of treatment were completed. Twelve patients (40%) experienced grade III/IV neutropenia. Five patients (16.6%) had grade III/IV anemia. There were two episodes of grade III/IV thrombocytopenia. The main nonhematological toxicities consisted of grade III nausea (13%) and grade III vomiting (13%). The most frequently reported disease-related symptoms at baseline were dyspnea, cough, and fatigue. There was a subsequent improvement in patient scores of dyspnea in 17% of patients, 31% showed improvement in cough, and 32% showed improvement in fatigue. The mean area under the curve of TPT following 2.3 mg/m2 p.o. was 51.6 ng.h/ml (%SD, 25%). The area under the curve of TPT on day 1 of the first cycle was correlated with the percentage fall in leukocytes. Although oral TPT at the applied dose and schedule showed modest activity as a single agent, almost one-half of the patients had a stable disease, and median time to progression was 12.3 weeks. The overall median survival was a promising 39.9 weeks, and useful palliation of symptoms was seen.

Administration, Oral↗

Development and validation of a sensitive solid-phase extraction and high-performance liquid chromatography assay for the novel antitumour agent CT2584 in human plasma.

A HPLC assay and solid-phase extraction technique from human plasma has been developed and validated for the novel anticancer agent CT2584, 1-(11-dodecylamino-10-hydroxyundecyl)-3,7-dimethylxanthine, which has recently completed a phase I trial at the Christie Hospital, Manchester under the auspices of the CRC phase I/II committee. Following addition of CT2576, 1-(11-octylamino-10-hydroxylundecyl)-3,7-dimethylxanthine, as internal standard, a solid-phase extraction cartridge (100 mg cyanopropyl) was used to isolate the drug CT2584 from human plasma. Analysis was performed by reversed-phase chromatography. CT2576 was used as internal standard at a concentration of 4 microg ml(-1) for the quantification of CT2584 from plasma for the duration of this work. The lower limit of quantification for the drug CT2584 in buffer using this assay was found to be 0.0122 microM (0.008 microg ml(-1)) and 0.048 microM (0.027 microg ml(-1)) when extracted from human plasma.

Antineoplastic Agents↗

Ovarian Burkitt lymphoma: pelvic pain in a woman with AIDS.

BACKGROUND: Non-Hodgkin lymphomas, a common AIDS-defining manifestation of human immunodeficiency virus (HIV), are aggressive, advanced at diagnosis, and tend to involve extranodal sites. Burkitt lymphoma comprises approximately 20% of AIDS-related non-Hodgkin lymphomas. Sites frequently affected by the disease include the central nervous system, bone marrow, gastrointestinal tract, and mucocutaneous tissue. Gonadal involvement is less common; reports of testicular lymphomas in adult males with AIDS have been sporadic. Ovarian involvement in AIDS-related lymphoma is exceedingly rare and usually involves pediatric patients. CASE: We report an unusual case in which disseminated Burkitt lymphoma presented as pelvic pain in a 32-year-old woman with AIDS. At laparoscopy, the ovaries were unremarkable in appearance but at the upper limits of normal size. However, extreme friability of the left ovary led to hemorrhage and oophorectomy. Pathologic evaluation of the ovary resulted in the diagnosis of Burkitt lymphoma. CONCLUSION: With improved survival because of antiretroviral therapy, the incidence of AIDS-related lymphomas is expected to rise. Lymphoma should be considered in the differential diagnosis of women with AIDS with perplexing abdominal or pelvic symptoms.

Adult↗

Nevirapine resistance mutations of human immunodeficiency virus type 1 selected during therapy.

Drug susceptibility and mutations in the reverse transcriptase (RT) gene were analyzed with 167 virus isolates from 38 patients treated with nevirapine, a potent nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) RT. Resistant isolates emerged quickly and uniformly in all patients administered nevirapine either as monotherapy or in combination with zidovudine (AZT). Resistance developed as early as 1 week, indicating rapid turnover of the virus population. The development of resistance was associated with the loss of antiviral drug activity as measured by CD4 lymphocyte counts and levels of HIV p24 antigen and RNA in serum. In addition to mutations at amino acid residues 103, 106, and 181 that had been identified by selection in cell culture, mutations at residues 108, 188, and 190 were also found in the patient isolates. Sequences from patient clones documented cocirculating mixtures of populations of different mutants. The most common mutation with monotherapy, tyrosine to cysteine at residue 181, was prevented from emerging by coadministration of AZT, which resulted in the selection of alternative mutations. The observations documented that, under selective drug pressure, the circulating virus population can change rapidly, and many alternative mutants can emerge, often in complex mixtures. The addition of a second RT inhibitor, AZT, significantly altered the pattern of mutations in the circulating population of HIV.

Antiviral Agents↗

Blueprint for integrating nurse extenders in critical care.

As more and more hospitals use the techniques of work restructuring to reduce their operating budget, no nursing department can escape change. Intensive care units can effectively and economically change skill mix by using a design that incorporates essential staff input and a structured educational program. Implementing a Patient Care Specialty Technician role in critical care serves as a driving force to control costs while maintaining quality care and patient satisfaction.

Cost Control↗