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Biomedical subjects

E Wiltshaw

Publications and source records attributed to E Wiltshaw.

At least 19 recordsLinked to original sources

Ifosfamide is an active drug for chemotherapy of metastatic cystosarcoma phyllodes.

Metastases from cystosarcoma phyllodes are rare, and treatment generally is ineffective. Four patients were treated with ifosfamide (alone in three and combined with doxorubicin in one). Two patients had complete remissions that lasted 26 and 61+ months. One other patient had a partial response that lasted 13 months. The complete responders were both treated as soon as metastases appeared, when they had only a small volume of disease. This appears to represent a significant improvement on other described regimens for this condition, and further trials of ifosfamide are warranted. Close follow-up of patients at high risk for metastases is suggested.

Adult

The clinical and histologic criteria that predict metastases from cystosarcoma phyllodes.

A retrospective study of 33 patients with cystosarcoma phyllodes was done. Eight of these patients had metastases, and the clinical and histologic criteria predicting the development of metastases were examined. The most reliable predictor was the presence of stromal overgrowth; this appears to be necessary for metastasis to occur. Other useful indicators of clinical behavior were the degree of mitotic activity, nuclear pleomorphism, and infiltrating margins. Based on these data and a literature review, the authors suggest close follow-up of patients whose primary tumors contain areas of stromal overgrowth because, in all series combined, the risk of metastatic spread in such patients was 72% within 5 years. Among these high-risk patients, local recurrence is another indication that metastasis is likely.

Adolescent

A phase II study of sulofenur, a novel sulfonylurea, in recurrent epithelial ovarian cancer.

A total of 16 patients with recurrent epithelial ovarian cancer were treated with sulofenur (LY 186641), a novel oral sulfonylurea. All subjects had received previous chemotherapy. Anaemia occurred in all 16 patients, 14 of whom required a blood transfusion, and 2/16 patients received methylene blue for breathlessness due to methaemaglobinaemia. Treatment was discontinued in 2/16 cases due to rising liver enzyme values, which reverted to normal on cessation of the drug. There was no nausea or alopecia. Only two minor responses were seen. Plasma drug levels were insufficient to result in antitumour activity as extrapolated from animal data. Further studies that attempt to increase the bioavailability and improve the therapeutic index are warranted.

Adolescent

Lymphomas of the cervix and upper vagina: a report of five cases and a review of the literature.

Five cases of non-Hodgkin's lymphoma of the cervix or upper vagina presenting over the last 20 years are described. The international literature has been reviewed for similar cases and a further 72 found. In 37 of these cases the pathology had been described according to one of the modern lymphoma classifications and details of clinical presentation, staging, treatment, and outcome were adequately described. The management and outcome of these patients have been critically reviewed and recommendations for the management of patients presenting with this disease have been made.

Adult

Hypersensitivity reactions to cisplatin and carboplatin--a report on six cases.

Anaphylactic reactions to platinum compounds are well recognised, but uncommon. These vary from true type I reactions to direct histamine release due to nonimmunological mechanisms. We present 6 cases to illustrate this--5 due to cisplatin and a report of this occurring with carboplatin--with a near fatal outcome in 3 of the cases.

Adult

Relationships between carboplatin exposure and tumor response and toxicity in patients with ovarian cancer.

PURPOSE: The study was undertaken to define the relationship between tumor response and carboplatin area under the curve (AUC) in patients with ovarian cancer; to study the relationship between carboplatin AUC and myelosuppression in the same population; to establish the true impact of carboplatin AUC, prior therapy, and pretreatment platelet and WBC counts on toxicity; and to define an optimal carboplatin exposure for treating patients with ovarian cancer. METHODS: With the equation AUC = dose/(glomerular filtration rate [GFR]+25), carboplatin AUC (course 1) was calculated for 1,028 patients (450 previously untreated) who received single-agent carboplatin (40 to 1,000 mg/m2) for advanced ovarian cancer. GFR was measured (chromium-51-edathamil [51Cr-EDTA] or creatinine clearance) in all patients. RESULTS: Regression analysis showed that carboplatin AUC, prior treatment, and Eastern Cooperative Oncology Group grade performance status (PS) are predictors of tumor response, thrombocytopenia, and leukopenia. Pretreatment platelet and WBC counts are additional predictors of thrombocytopenia and leukopenia, respectively. Although the likelihood of tumor response increased with increasing carboplatin AUC, this relationship was nonlinear. In all patient subsets, the likelihood of complete response (CR) or overall response did not increase significantly above a carboplatin AUC of 5 to 7 mg/mL x minutes. At any given carboplatin AUC, thrombocytopenia occurred more frequently than leukopenia, although both approached 100% as carboplatin AUC increased. Both thrombocytopenia and leukopenia were more frequent in pretreated than in untreated patients regardless of pretreatment count. At any carboplatin AUC, the influence of PS on likelihood of response and toxicity was profound. CONCLUSION: Carboplatin dosing by AUC will lead to more predictable toxicity, and increasing carboplatin AUC above 5 to 7 mg/mL x minutes does not improve the likelihood of response but does increase myelotoxicity. Therefore, careful evaluation of high-dose carboplatin therapy in a prospective, randomized trial is needed before such treatment becomes accepted practice.

Aged

Hormone replacement therapy and survival after surgery for ovarian cancer.

OBJECTIVE: To evaluate whether hormone replacement therapy affects survival in women who have undergone bilateral salphingo-oophorectomy because of epithelial ovarian cancer. DESIGN: Retrospective analysis by review of patients' notes and questionnaires completed by general practitioners to compare the overall survival and disease free survival in patients with ovarian cancer who did or did not receive hormone replacement therapy after diagnosis. Data were analysed by Cox regression, with hormone replacement therapy as a time dependent covariate because patients who received hormone replacement did so at different times after diagnosis. SETTING: Gynaecological oncology unit of Royal Marsden Hospital. PATIENTS: 373 patients aged 50 years or younger who attended the hospital from 1972 to 1988. All of the women had undergone bilateral salpingoophorectomy for epithelial ovarian cancer. In all, 78 had received hormone replacement therapy, starting at a median of four months after diagnosis. INTERVENTION: A questionnaire was sent to the general practitioners of all patients who were not recorded as having received hormone replacement therapy. MAIN OUTCOME MEASURES: Overall survival and disease free survival. RESULTS: There was no significant difference in survival between women receiving hormone replacement therapy and those not receiving it after accounting for the effects of other known prognostic factors (stage of cancer, differentiation of tumour, histological results, and time to relapse). The relative risk of dying in those who received hormone replacement therapy was 0.73 (95% confidence interval 0.44 to 1.20). In addition, there was no significant difference in disease free survival (relative risk in those receiving hormone replacement therapy was 0.90; 95% confidence interval 0.52 to 1.54). CONCLUSIONS: This study shows that hormone replacement therapy is unlikely to have a detrimental effect on the prognosis of patients with ovarian cancer, but this would be shown conclusively only by a randomised controlled trial.

Adult

Retroconversion of immature teratoma of the ovary: CT appearances.

We have studied seven patients presenting to the Royal Marsden Hospital between 1983 and 1989 with metastatic immature teratoma of the ovary. All patients underwent initial surgery followed by combination chemotherapy and a second laparotomy. Serial CT scans were performed at 2-3 monthly intervals from diagnosis until the second laparotomy, and the results of this were correlated with the CT appearances. In six of the seven patients CT scanning demonstrated 'retroconversion' of immature malignant tumour masses to benign mature disease during treatment. CT features of maturation included increased density of mass lesions, whose margins became better circumscribed in relation to adjacent tissues, and the onset of internal calcification, with fatty areas and cystic change. These changes on CT correlated exactly with normalization of an initially raised serum tumour marker, alpha feto-protein (AFP) in all six patients. The second laparotomy revealed only mature teratoma in all patients following chemotherapy. In three patients show continued growth of the mature deposits necessitated further surgery for local pressure symptoms, but overall, none has shown malignant relapse, and all are currently well between 1 and 6 years after diagnosis. This is the first report of the CT appearances of retroconversion of immature ovarian teratoma in a series of patients, which is an important radiological diagnosis to make in order to avoid confusion with advancing malignancy. A review of the literature is presented.

Adolescent

Phase II trial of trimelamol in refractory ovarian cancer.

Trimelamol is an analogue of hexamethymelamine which exhibited activity against refractory ovarian cancer in phase I clinical trial. The dose limiting toxicity was leukopenia. In a phase II study, 42 patients with recurrent, or platinum-complex resistant, advanced ovarian cancer were treated using the dose schedule 800 mg m-2 i.v. daily for 3 days. There were one complete, three partial and five minor responses, objective response rate: 9.5%. The main toxicity observed was nausea and vomiting, myelosuppression was minor. The role of Trimelamol in the treatment of ovarian cancer remains to be defined, but its activity is limited in refractory disease.

Adult

Serial cytogenetic studies showing persistence of original clone in Hodgkin's disease.

A case of Hodgkin's disease is described in which cytogenetic studies were performed at intervals for 5 years. Clonally related chromosomally rearranged cells persisted during that time, with emergence of more complex karyotypes in the terminal phase of the disease. The chromosome findings are discussed in relation to the limited data available on banded karyotypes in Hodgkin's disease.

Bone Marrow Cells

Ifosfamide with and without adriamycin in advanced uterine leiomyosarcoma.

Uterine leiomyosarcomas are rare tumours and the results of treatment of advanced disease are poor. Ifosfamide and Adriamycin are both known to be active drugs in soft-tissue sarcomas. We present our experience using ifosfamide alone and in combination with Adriamycin in advanced or recurrent uterine leiomyosarcomas. Ifosfamide alone was given as a 24-h infusion at doses ranging from 5 to 7.5 g/m2, with mesna rescue. In the combination regimen, ifosfamide was given at a dose of 5 g/m2 and Adriamycin, at a dose of 40 or 60 mg/m2. Ten patients were treated with ifosfamide alone, with only one partial response lasting 6 months. In all, 11 patients were treated with ifosfamide and Adriamycin, which resulted in 1 complete response that lasted 11 months. Although many of the patients had extensive disease and some had undergone prior treatment with other chemotherapy, ifosfamide would appear to have only modest activity at the dose and schedule used.

Adult

Carboplatin and ifosfamide in ovarian cancer phase II and III trials. London Gynaecological Oncology Group.

Over the past few years controversy has continued as to whether alkylating agents such as cyclophosphamide or chlorambucil are as effective as cisplatin in advanced ovarian cancer. Arguments have also been put forward against the use of combination chemotherapy, which is clearly more toxic than single-agent treatment and is probably no more effective than a single-agent platinum compound except in terms of producing a higher response rate. Certainly survival is not improved.

Antineoplastic Agents

A phase II study of ifosfamide and cisplatin chemotherapy for metastatic or relapsed carcinoma of the cervix.

A total of 44 women received a combination of ifosfamide (1.5 g/m2 daily x5) and cisplatin (50 mg/m2 on day 1 only) as first-line chemotherapy for recurrent or metastatic carcinoma of the cervix. In all, 12/42 (38%) evaluable patients responded, with the median duration of response being 7 months. Bone marrow and gastrointestinal toxicity were frequently severe. There were 3 septic deaths. Although cisplatin plus ifosfamide is an active combination against this disease, these results suggest that it is no more so than either drug used alone.

Adult