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Biomedical subjects

S G Allan

Publications and source records attributed to S G Allan.

At least 19 recordsLinked to original sources

Adjuvant chemotherapy for non-metastatic osteosarcoma of the extremities in two New Zealand cancer centres.

BACKGROUND: Adjuvant chemotherapy significantly improves survival of patients with non-metastatic osteosarcoma but most of the data come from trials conducted in major international cancer centres. AIM: To review the efficacy and toxicity of an adjuvant chemotherapy regimen used in two regional cancer centres in New Zealand. METHODS: Retrospective review of patients treated for non-metastatic high-grade osteosarcoma of the extremities. The regimen (POMA) consists of high-dose-methotrexate 8 g/m2 and vincristine 1.5 mg/m2 (maximum 2 mg) on days 1 and 8 followed by folinic acid then doxorubicin 50 mg/m2 and cisplatin 100 mg/m2 on day 15. This cycle was repeated every 35 days. Following amputation patients received six cycles while in selected patients two cycles were planned prior to limb salvage surgery followed by a further four cycles. Actuarial survival was calculated using the Kaplan-Meier method. RESULTS: Twenty patients were treated with POMA between 1986 and 1993. Amputation was performed in 16 patients and limb-salvage surgery in four. Sixteen patients (80%) remain alive with no evidence of disease at a median follow-up of 40 months. Thirteen patients (65%) have been continuously disease-free. Actuarial survival at five years is 70%. Seven patients relapsed, six in lungs, of whom four underwent pulmonary metastasectomy; three of these remain free of disease 31, 35 and 40 months later. There was no local relapse. The toxicity of POMA is significant but tolerable. CONCLUSION: The results obtained at two regional cancer centres in New Zealand using POMA compare favourably to those achieved in clinical trials performed at major international cancer centres.

Adolescent↗

Ondansetron reduces chemotherapy induced nausea and vomiting refractory to standard antiemetics.

Ondansetron, a selective 5HT3 (serotonin) antagonist, was used in patients refractory to standard antiemetics. Seventy-five patients receiving chemotherapy without cisplatin were given ondansetron 4 mg IV and 4 mg orally immediately prior to chemotherapy, then 8 mg orally after six and 12 hours, followed by 8 mg orally eight hourly during days 2-5. Complete control of vomiting occurred in 52 patients (69%) on the first day and 45 patients (60%) on days 2-5. Sixty patients (80%) preferred ondansetron to their previous antiemetics. The efficacy of ondansetron was maintained over multiple chemotherapy cycles. Ondansetron was also given to 16 patients receiving cisplatin chemotherapy. They received 8 mg IV immediately prior to chemotherapy followed by an infusion of 1 mg/hr for 8 hr, with 8 mg orally at the end of the infusion and then 8 mg orally eight hourly during days 2-6. Some control of vomiting (less than = 5 vomits) was achieved in eight patients (50%) on the first day and in 14 patients (87%) on subsequent days. Eight patients (50%) preferred ondansetron to their previous antiemetics. Adverse events with ondansetron were frequent but mild, with constipation and headache being most common. Ondansetron is highly effective in patients refractory to standard antiemetics, especially after noncisplatin chemotherapy.

Adult↗

Antiemetics.

This article explores recent knowledge on the physiology and neuropharmacology of the emetic process. It seeks to outline the indications for specific antiemetic drugs and where their actions are targeted. Much of the information for the role of antiemetic drugs has come from experience with antiemetics in patients receiving cytotoxic chemotherapy. The role of the new 5-HT3 receptor antagonists is outlined, with special reference to ondansetron.

Antiemetics↗

Does dexamethasone enhance control of acute cisplatin induced emesis by ondansetron?

OBJECTIVE: To determine the contribution of dexamethasone to the efficacy of the 5-hydroxytryptamine antagonist ondansetron in control of cisplatin induced nausea and vomiting. DESIGN: Randomised double blind crossover study. SETTING: Two cancer centres in teaching hospitals, one in the United Kingdom and the other in Germany. SUBJECTS: 100 patients (53 men and 47 women) new to cisplatin chemotherapy, 84 of whom completed two consecutive courses of chemotherapy. INTERVENTIONS: Patients were given intravenous dexamethasone (20 mg) or physiological saline with intravenous ondansetron 8 mg before cisplatin, then ondansetron 1 mg/h for 24 hours. Oral ondansetron 8 mg was taken three times daily on days 2-6. MAIN OUTCOME MEASURES: Incidence of complete or major control of emesis (0-2 episodes in the 24 hours after chemotherapy). RESULTS: Complete or major control was obtained in 49 out of 71 (69%) of patients after receiving ondansetron plus dexamethasone compared with 40 out of 71 (56%) when they were given ondansetron alone (p = 0.012). This effect was most pronounced in the first 12 hours after chemotherapy. Patients receiving the combination also had significantly less nausea. Of the 53 patients who expressed a preference, 38 (72%) preferred the combination treatment (p = 0.002) to ondansetron alone. The effect of ondansetron on delayed emesis was less pronounced. CONCLUSIONS: Dexamethasone makes a significant contribution to the efficacy of ondansetron in the control of acute platinum induced emesis.

Acute Disease↗

Phase I study of the anthrapyrazole biantrazole: clinical results and pharmacology.

In a phase I study the anthrapyrazole biantrazole (Warner-Lambert Company) was given to 41 patients with tumour refractory to existing therapy. The drug was given i.v. weekly for 3 weeks, with a 3-week interval between courses. At the 1st week a full pharmacokinetic study was performed, and at weeks 2 and 3, blood samples were taken at 1 and 6 h following treatment to check for drug accumulation. Biantrazole pharmacokinetics were linear with respect to the AUC (r = 0.924) over the full range of doses studied (4-36 mg/m2) but exhibited large inter-patient variations at each dose level. Elimination was triphasic, comprising two rapid early phases and a long terminal half-life (mean, 14.1 +/- 7.8 h). There was no evidence of drug accumulation over the 3-week treatment period. Approximately 12% of the parent drug was excreted unchanged in the urine together with two non-circulating, more water-soluble metabolites. Biantrazole was well tolerated but did cause moderate emesis at doses of greater than 18 mg/m2 and mild alopecia. The dose-limiting side effect was leucopenia, with no other major toxicity being observed. One patient developed biventricular failure that was not clearly related to biantrazole administration. On the present schedule, the recommended dose of biantrazole is 24 mg/m2. No response were seen in this patient population.

Adolescent↗

A 10-year experience of tamoxifen as primary treatment of breast cancer in 100 elderly and frail patients.

Between 1977 and 1983 100 elderly women (median 76.3 years) with breast cancer were treated with tamoxifen as primary therapy. The median follow-up is 59 months. Sixty-eight responded (40 CR and 28 PR) with median response durations of 47 months and 26 months respectively. Twenty-two patients had disease stabilization for a median of 15.5 months and 10 had progressive disease. The median time to best response was 13.5 weeks for patients achieving CR and 14 weeks for those with PR. Oestrogen receptor values were obtained in 37 patients of which two patients had no ER detectable. Sixty-seven per cent of ER-unknown patients responded compared with 74% of ER-rich. Likelihood of response did not appear to depend upon T-stage or age. Survival was better than that of an unmatched historical group treated with surgery/radiotherapy and compares favourably with recent reports. Although 35% have died of breast cancer, 25% died of other causes and 22% remained free of recurrence at the time of reporting or at death. Only 11% underwent subsequent mastectomy/lumpectomy and the most frequent subsequent treatments were radiotherapy to the breast (32%) and further hormonal therapies (40%). Tamoxifen is a practical primary therapy of breast cancer in elderly and frail women obviating the need for surgery in a high proportion of cases.

Aged↗

Prognosis at presentation of small cell carcinoma of the lung.

Prognostic factors in 411 patients with small cell lung carcinoma have been retrospectively analysed. Univariate analysis of continuous variables showed that prognosis was worse with deteriorating performance status, extensive disease, positive bone scan, increasing age, elevated total white cell count, alkaline phosphatase, lactate dehydrogenase, and decreased serum chloride and albumin. Low serum sodium was less clearly associated with poor survival. Cox multivariate regression showed that performance status, disease extent, age and raised lactate dehydrogenase and white cell count were independent prognostic factors. When disease extent was excluded from analysis, performance status, age, total white cell count, lowered serum chloride and raised lactate dehydrogenase were significant independent prognostic variables.

Adult↗

Potentiation of cisplatin by alpha-interferon in advanced non-small cell lung cancer (NSCLC): a phase II study.

Studies in experimental human lung cancer models have suggested that interferon may enhance significantly the response to some cytotoxic drugs. We have performed a phase II study of cisplatin (100 mg/m2 q.21 or 28 days) and alpha-2 interferon (3 or 5 MU three times weekly) in 68 patients with advanced non-small cell lung cancer and good performance status. As toxicity was acceptable, the dose of interferon and schedule of cisplatin were increased at the midpoint of the study. 46% (11/24) of patients with squamous carcinoma responded and an overall partial response rate of 30% was attained in 60 evaluable patients. There was no potentiation of haematological, renal or neurological toxicity but nausea and vomiting were severe. These results suggest that the combination has activity in this usually refractory disease.

Adult↗

Influence of therapy on local control and survival in stage I and II intermediate and high grade non-Hodgkin's lymphoma.

In a consecutive series of 113 patients with localized (Stage I and II) intermediate and high grade non-Hodgkin's lymphoma we have retrospectively analysed patterns of survival and relapse in relation to presenting features and therapy. Two patients were treated by complete surgical excision. Seventy-two were treated by radiotherapy (RT), 19 by chemotherapy (CT) and 20 by combined CT and RT. A number of different chemotherapy combinations were employed. Overall survival for Stage I patients was 68.3% at 5 years and 65.5% at 10 years; for Stage II patients it was 61.2% at 5 years and 52.2% at 10 years. Recurrence-free survival for Stage I patients was 51.4% at 5 years and 42.1% at 10 years; for Stage II patients it was 46.2% at both 5 and 10 years. Local control by radiation was achieved in 59/72 (82%) patients treated with less than 40 Gy and 19/20 (95%) treated with 40 Gy or more. There was no advantage for extended field irradiation when compared with involved field. Eleven of 19 (58%) patients treated by CT alone achieved complete response (CR). For patients responding completely to CT there was no clear advantage for irradiation of originally involved bulky sites. For patients with Stage II and bulky Stage I disease there was a significant (P = 0.05) improvement in recurrence-free survival (RFS) and a trend (P = 0.192) towards improved overall survival for patients treated by CT alone or together with RT compared with RT alone. Independent variables identified by multivariate analysis were age, with better survival for younger patients (P = 0.034) and histopathological group, with better survival for DPDL compared with DH (P = 0.015).

Adolescent↗

Low grade stage I and II non-Hodgkin's lymphoma: results of treatment and relapse pattern following therapy.

Sixty-four patients (37 stage I and 27 stage II) with low grade non-Hodgkin's lymphoma were treated by surgical excision alone (two patients) or with radiotherapy (53 patients), chemotherapy (five patients) or both (four patients). Actuarial survival was 80.7% at 5 years and 77.9% at 10 years. Actuarial recurrence-free survival at 10 years was 49.4% for stage I and 38.0% for stage II patients. Local control was achieved in 52 out of 56 (93%) patients treated with a radiation dose of 30 Gy or greater. There was no advantage for extended compared with involved, field irradiation. A multivariate analysis identified age, sex, stage and disease site as independent prognostic variables for survival.

Adult↗

Mechanisms and management of chemotherapy-induced nausea and vomiting.

Only in recent years has serious attention been given to the control of chemotherapy-induced emesis (CIE) which is to the patient a most obnoxious side-effect. Important advances in the understanding of the mechanisms of CIE have led to the scientific appraisal of potential anti-emetics whilst additional, useful anti-emetics have appeared by serendipity. CIE has largely been studied in trials separating either cis-platinum (severely emetic) or non-cis-platinum(moderately emetic)-induced emesis. In the evolution of these trials the difficulty and importance of accurate evaluation of emesis has been revealed and the whole area of psychogenic emesis opened to investigation and treatment. Phenothiazines and butyrophenones have a definite modest anti-emetic role against moderately emetogenic chemotherapy but increasingly corticosteroids, benzodiazepines, high dose metoclopramide and cannabinoids are being used with great effect even with severely emetic drugs. Combination anti-emesis has further improved control rates and new schedules of currently available anti-emetics are now proving their worth. Major advances in anti-emetic control have been achieved recently and every patient at risk of CIE should have good control, if not total abolition, of emesis with appropriate use of anti-emetics.

Antineoplastic Agents↗

Prognosis in small cell carcinoma of the lung--relationship to human milk fat globule 2 (HMFG2) antigen and other small cell associated antigens.

Forty fixed tissue sections from patients with small cell lung carcinoma (SCCL) have been stained with a panel of 10 monoclonal antibodies using a peroxidase anti-peroxidase method and the incidence of staining has been compared to patient characteristics at presentation and to survival. An inverse association between HMFG2 staining and survival was found with median survival in HMFG2 negative patients 13 months compared to 8 months for HMFG2 positive patients. No such association was found with the other antibodies and no association was found between staining and disease extent or primary versus secondary deposits with this panel of antibodies. Epidermal growth factor receptor was detected in 3/38 presentation biopsies and in these 3 patients mean survival was only 5 months. Further prospective study of HMFG2 as a prognostic indicator in SCCL is suggested.

Antigens, Neoplasm↗