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Biomedical subjects

R Stuart-Harris

Publications and source records attributed to R Stuart-Harris.

At least 37 records · Page 2Linked to original sources

Renal phosphate threshold and response to pamidronate in humoral hypercalcaemia of malignancy.

The effect of a single dose of pamidronate was studied in 15 patients with hypercalcaemia of malignancy. All patients were hydrated with saline 24 h before and 48 h after treatment. The dose of pamidronate was 30-90 mg intravenously, depending on corrected calcium level after hydration. Patients were retrospectively divided into two groups according to response to pamidronate. Corrected calcium fell to normal or below the upper limit of normal within a median of 3 days after treatment in 7 well controlled patients. In 8 poorly controlled patients corrected calcium failed to return to normal and in 7 of these, corrected calcium increased within 8 days of treatment. The best single indicator of a potent renal mechanism for the hypercalcaemia and also a poor response to pamidronate was a low renal phosphate threshold. Negative isotopic bone scans were also more common in poorly controlled patients.

Bone Neoplasms↗

Focal encephalopathy after cisplatin therapy.

Focal encephalopathy after cisplatin therapy, although described previously, is a rare adverse effect. Recently, four patients who received cisplatin therapy at our institution developed focal encephalopathy which manifested itself as cortical blindness, aphasia with seizures, aphasia with hemianopia and a focal seizure, respectively, shortly after the administration of cisplatin. Each episode occurred while the patients were febrile with neutropenia although no evidence of central nervous system infection was found. The neurological symptoms occurred after at least two courses of cisplatin therapy (minimum total cisplatin dose, 300 mg/m2) and three of the four patients also were noted to have hypomagnesaemia. In each case, the neurological deficit resolved and two patients received further cisplatin therapy without a recurrence of the neurological symptoms. Our experience suggests that focal encephalopathy that is associated with cisplatin therapy may resolve completely with supportive measures alone and need not preclude further therapy with cisplatin.

Adolescent↗

Empiric single agent or combination antibiotic therapy for febrile episodes in neutropenic patients: an overview.

Febrile episodes during chemotherapy-induced neutropenia are a frequent cause of morbidity and mortality in cancer patients. Empiric antibiotic therapy commencing at the onset of fever is selected according to three principles: intravenous therapy is used to rapidly achieve bactericidal serum levels, antibiotics with appropriate antibacterial spectra are required, and combinations of antibiotics have been preferred for their synergistic activity. Initial empiric monotherapy with single antibiotics such as imipenem which have a sufficiently broad antibacterial spectrum in their own right are potentially as efficacious as conventional combination therapies. Granulocytopenic periods complicated by fever are significantly longer in patients receiving chemotherapy for leukaemia than in patients undergoing treatment for lymphoma and solid tumours. However, defervescence of fever following commencement of antibiotic therapy occurs equally rapidly in these three groups. The persistent granulocytopenia leaves leukaemic patients at greatest risk of breakthrough or second infections. These patients therefore appear to be the most likely to benefit from the clinical use of haemopoietic growth factors such as granulocyte and granulocyte-macrophage colony-stimulating factor.

Agranulocytosis↗

A phase I-II study of ifosfamide in combination with adriamycin in the treatment of adult soft tissue sarcoma.

Fifty-four patients with advanced soft tissue sarcoma were treated with a combination of ifosfamide (5 g/m2) and adriamycin (40-60 mg/m2) at 3 weekly intervals. Of the 50 evaluable patients a response was seen in 11 (22%) patients (3 complete and 8 partial responses), stabilization of disease occurred in 17 patients and the remaining 22 patients progressed whilst on treatment. Of the 22 patients receiving adriamycin 60 mg/m2 12 (55%) required a dose reduction due to toxicity compared to 11 (39%) of the 28 patients who received 40 mg/m2. For the patients who had a response the median relapse-free interval was 7 months (range 2-17+) and the overall median survival was 12 months (range 5-29+). The combination does not appear to show an advantage over either drug used as a single agent.

Adolescent↗

Patient treatment preference in advanced breast cancer: a randomized cross-over study of doxorubicin and mitozantrone.

Twenty-two patients with advanced breast cancer participated in a randomized cross-over study of one cycle each of doxorubicin followed 3 weeks later by mitozantrone or vice versa. Before further treatment, patients selected which drug they wished to continue. Of 18 patients completing the study, 13 chose to continue mitozantrone, 2 doxorubicin and 3 had no preference (P = 0.007). Patients were told to assume similar efficacy of the two drugs and drug preference was based primarily on side-effects. Patient self-assessment of quality of life and physician assigned toxicity scores both indicated that nausea and vomiting, appetite and alopecia were significantly worse following doxorubicin than after mitozantrone. Except for alopecia, no significant period or carry-over effects were noted although the power of the study to detect such interactions was low. This study design may prove useful in enabling patients to select their preference between two treatments of similar efficacy.

Adult↗

Chemotherapy for small cell lung cancer: induction and reinduction with VOCA.

Sixty-five patients with small cell lung cancer were treated with VP16, vincristine, cyclophosphamide, and doxorubicin (VOCA) intravenously at three-week intervals. Patients with limited disease received four cycles with responders receiving radiation to the primary site and prophylactic cranial irradiation. Patients with extensive disease received chemotherapy only. Of 59 patients evaluable for chemotherapy response, eight (14%) achieved complete remission and 30 (51%) partial remission. Major side-effects included myelosuppression, alopecia, nausea, and vomiting. Reinduction with VOCA at relapse yielded objective or subjective response in four of seven patients. This regimen is active in small cell lung cancer and was well tolerated by patients. Reinduction of response was possible in a small number of patients retreated and may provide useful palliation for those who relapse when treatment is discontinued.

Adult↗

Carboplatin (CBDCA, JM-8) and VP-16-213 in previously untreated patients with small-cell lung cancer.

The efficacy and toxicity of carboplatin 100 mg/m2, administered intravenously (IV) daily X 3, and VP-16-213 120 mg/m2, IV daily X 3, administered every 28 days for six courses, was assessed in 94 (36 limited stage, 58 extensive stage) previously untreated patients with small-cell lung cancer. Mediastinal irradiation using 50 Gy in 25 fractions was given to all limited-stage patients with a complete (CR) or partial response (PR) after three chemotherapy courses. Cranial irradiation was administered to all patients with CR. Objective responses were seen in 77% (CR 40%, PR 37%) of patients with limited-stage and 58% (CR, 9%; PR, 49%) with extensive-stage disease. Median relapse-free survival for objective responders with limited stage was 14.6 months and 7.9 months for extensive-stage patients. Median relapse-free survival following CR was 15.4 months and 8.5 months for PR. Median survival was 15.3 months for limited-stage and 8.1 months for extensive-stage patients. The combination was well tolerated with mild nausea or less (World Health Organization [WHO] grade 0 or 1) in 62% of patients and minimal mucositis, renal, neurotoxicity, or ototoxicity. Neutropenia less than 1.0 X 10(9)/L (WHO grade 3 or 4) was seen in 63% of patients, with two deaths from infection while neutropenic. The combination of carboplatin and VP-16-213 is a new, active program with low toxicity when applied intensively in previously untreated patients with small-cell lung cancer.

Adult↗

Extraskeletal Ewing's sarcoma: a clinical, morphological and ultrastructural analysis of five cases with a review of the literature.

In 1969 it was recognised that tumors with light microscopic appearances indistinguishable from Ewing's sarcoma of bone may arise in extraskeletal sites (extraskeletal Ewing's sarcoma). Here, we review the available literature and report five new cases. All five received combined modality therapy with combination chemotherapy and radiotherapy to the primary site followed by surgical excision in two. All attained complete remission; after a median follow-up of 26 months, three remain disease-free but two have relapsed and died. Our experience, in accord with previous series, suggests that extraskeletal Ewing's sarcoma compared with its bony counterpart tends to occur in older subjects, has a similar incidence in males and females, usually presents with a painless mass and readily responds to combined modality therapy. We detected no light or electron microscopic features to denote a histogenetic origin. However, we suspect extraskeletal Ewing's sarcoma may occur more frequently than previously supposed.

Adult↗

Role of aminoglutethimide in male breast cancer.

Five men with advanced breast cancer were treated with aminoglutethimide (AG) plus replacement dose hydrocortisone. None of the 4 patients with intact testes responded, although 3 did so subsequently to tamoxifen. The previously orchidectomized patient responded to aminoglutethimide for 14 months. Oestrone and oestradiol were suppressed by AG in all patients, but not to the levels achieved by orchidectomy. AG produced substantial further oestrogen suppression in the orchidectomized patient and should only be used after orchidectomy.

Aminoglutethimide↗

Mitoxantrone as first-line chemotherapy in advanced breast cancer: results of a collaborative European study.

Mitoxantrone (Novantrone; dihydroxyanthracenedione) is a substituted anthraquinone with a spectrum of activity similar to doxorubicin in experimental tumors. One hundred and seventy three patients with advanced breast cancer and no prior cytotoxic therapy for advanced disease entered a phase II study of mitoxantrone, 14 mg/m2 i.v. repeated every 3 weeks. At the time of this analysis 116 patients were evaluable. Eight patients achieved a complete response and 27 a partial response, the overall response rate being 30% (95% confidence limits: 22-39%). The median time until response was recorded was 15 weeks. The median duration of response was 74+ weeks and the median time to progression or death for all 116 patients was 22+ weeks. Mitoxantrone was well tolerated with myelosuppression as the dose-limiting toxicity. The most frequent non-haematological toxicities were nausea and vomiting (65%) but they were rarely severe. Total alopecia occurred in only 6% of the patients. Four patients developed clinically significant evidence of cardiotoxicity after cumulative mitoxantrone doses of 174-256 mg/m2. Thus, mitoxantrone offers comparable efficacy and less acute toxicity than the most active single agents currently available in the treatment of advanced breast cancer.

Adult↗

A comparison of the endocrine effects of low dose aminoglutethimide with and without hydrocortisone in postmenopausal breast cancer patients.

The endocrine effects of 125 mg (low dose) aminoglutethimide (AG) twice daily (b.d.) were compared with those of 125 mg AG + 20 mg hydrocortisone (HC) b.d. in 23 and 45 postmenopausal patients with advanced breast cancer, respectively. The patients in each group were drawn from two separate populations, but the mean age and weight of the groups were similar and there were no significant differences between the pretreatment serum levels of the hormones investigated. Serum oestrone and oestradiol levels were suppressed by both treatments, but there was a significantly greater suppression by AG + HC. This greater suppression is probably due to the observed increase in serum androstenedione (i.e. precursor) levels with AG alone, whilst with AG + HC these levels were found to be reduced. In terms of suppression of serum oestrogen levels it is of benefit to combine low dose AG with HC.

Adult↗

Observations on the pharmacokinetics of low dose aminoglutethimide in patients with advanced breast cancer.

Serum aminoglutethimide (AG) and N-acetylaminoglutethimide (NAG) concentrations were measured by high pressure liquid chromatography (HPLC) in 24 postmenopausal women with advanced breast cancer receiving increasing doses of oral AG. Patients received 62.5 mg b.d., 125 mg b.d., 250 mg b.d., and 500 mg b.d. of AG alone, and 500 mg b.d. of AG combined with hydrocortisone (HC) 20 mg b.d. Dose was increased at monthly intervals. Each dose increment was accompanied by a significant rise in serum AG and NAG levels (P less than 0.05). The addition of HC to the dose of 500 mg b.d. of AG did not alter serum AG or NAG concentrations significantly. Although serum AG and NAG levels appeared to increase linearly with dose, serum NAG increased significantly more slowly, leading to a fall in the NAG:AG ratio during therapy. The NAG:AG ratio appeared to stabilise only after about 6 months of treatment.

Aged↗