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Biomedical subjects

G J Rustin

Publications and source records attributed to G J Rustin.

At least 91 records · Page 5Linked to original sources
PubMed1992

Phase II trials of fosquidone, (GR63178A), in colorectal, renal and non-small cell lung cancer. CRC Phase II Clinical Trials Committee.

A total of 61 eligible patients with metastatic cancer have been treated in a series of Phase II trials of the novel pentacyclic pyrroloquinone, fosquidone. Tumour types were colorectal (23), renal (21), and non small cell lung (17). No patient had received prior chemotherapy. The drug was given intravenously as a 20 min infusion at the dose of 120 mg-2 on days 1 to 5 every 3 weeks. Treatment was well tolerated; the only significant side effects being mild nausea and generalised musculo-skeletal pains. Response was assessed after two cycles of therapy. No patient achieved an objective partial response. A total of nine patients demonstrated stable disease for a median duration of 11 weeks. Using this schedule of administration, fosquidone has no significant antitumour activity in this group of tumours.

Adult↗
PubMed1992

Flavone acetic acid (FAA) with recombinant interleukin-2 (TIL-2) in advanced malignant melanoma. II: Induction of nitric oxide production.

Plasma samples were collected from 20 patients undergoing phase I clinical trial with flavone-8-acetic acid (FAA; 4.8 g m-2 per dose) in combination with recombinant human interleukin-2 (rhIL-2; 6-18 i.u. m-2 per day) for the treatment of metastatic melanoma. Samples were analysed for nitrate content as an indication of the oxidation of L-arginine to nitric oxide. Pretreatment plasma nitrate levels (53 +/- 4 microM) were significantly above those of healthy volunteers (19 +/- 4 microM). The maximum plasma nitrate concentration obtained after treatment, 190 +/- 29 microM (range 49 to 655 microM), was comparable to that of mice treated with FAA. Most of the increases occurred 3-5 days after initiation of a 5 day infusion of rhIL-2, but three of the increases occurred within 2 days of a 1 h infusion of FAA alone. The maximum plasma nitrate concentrations of the three patients which underwent remission (two complete, one partial) following treatment (368 +/- 143 microM) were significantly higher (P < 0.05) than those of patients with progressive disease. Hypotension was the major dose-limiting side effect, and there was no relationship between the degree of hypotension and the rise in plasma nitrate. The results provide evidence that treatment of patients with FAA and rhIL-2 induce the synthesis of nitric oxide, a physiological mediator and potential cytotoxic agent.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Phase I trial of temozolomide (CCRG 81045: M&B 39831: NSC 362856).

Temozolomide (CCRG 81045: M&B 39831: NSC 362856) is an analogue of mitozolomide displaying similar broad spectrum activity in mouse tumours, but showing considerably less myelosuppression in the toxicology screen. Temozolomide was initially studied intravenously at doses between 50-200 mg m-2 and subsequently was given orally up to 1,200 mg m-2. A total of 51 patients were entered on the single dose schedule. Temozolomide exhibits linear pharmacokinetics with increasing dose. Myelotoxicity was dose limiting. Experimentally, temozolomide activity was schedule dependent and therefore oral administration was studied as a daily x 5 schedule between total doses of 750 and 1,200 mg m-2 in 42 patients. Myelosuppression was again dose limiting. The recommended dose for Phase II trials is 150 mg m-2 po for 5 days (total dose 750 mg m-2) for the first course, and if no major myelosuppression is detected on day 22 of the 4 week cycle, the subsequent courses can be given at 200 mg m-2 for 5 days (total dose 1 g m-2) on a 4 week cycle. Mild to moderate nausea and vomiting was dose related but readily controlled with antiemetics. Clinical activity was detected using the 5 day schedule in four (2CR, 2PR; 17%) out of 23 patients with melanoma and in one patient with mycosis fungoides (CR lasting 7 months). Two patients with recurrent high grade gliomas have also had partial responses. Temozolomide is easy to use clinically and generally well tolerated. In the extended Phase I trial temozolomide only occasionally exhibited the unpredictable myelosuppression seen with mitozolomide.

Adult↗
PubMed1992

Single agent activity of carboplatin in patients with previously untreated non-seminomatous germ cell tumours.

The response to a single course of carboplatin has been investigated in 12 patients with previously untreated non-seminomatous testicular germ cell tumours. Patients received one course of carboplatin at a dose calculated to achieve a target area under the free carboplatin plasma concentration versus time curve (AUC) of 7 mg/ml x mins using the formula: dose (mgs) = target AUC x (GFR + 25). Response to carboplatin was assessed after a single course and treatment was then continued on the POMB/ACE schedule. Ten of 12 patients had either a greater than 50% decrease in serum HCG and/or AFP levels or a greater than 50% decrease in tumour volume after a single course of carboplatin. No patient had evidence of disease progression after carboplatin. This study demonstrates that single agent carboplatin is highly active in patients with non-seminomatous testicular germ cell tumours and thus provides evidence to justify its inclusion in chemotherapy combinations.

Carboplatin↗
PubMed1991

Pulmonary embolism, pulmonary hypertension, and choriocarcinoma.

A rare cause of pulmonary embolism and pulmonary artery hypertension in young women is choriocarcinoma growing in the pulmonary artery. This growth is reversible, and the disorder can be cured. We describe three patients with this feature who have been treated with appropriate high-risk chemotherapy and who are now in remission. Contrast-enhanced computed tomography can be used to identify major emboli, and progress of the disease can be monitored by serial ventilation/perfusion scans and measurement of serum human chorionic gonadotropin. Recognition of this rare syndrome is important because of the generally excellent outlook with appropriate treatment.

Adult↗
PubMed1991

Comparison of ondansetron and ondansetron plus dexamethasone as antiemetic prophylaxis during cisplatin-containing chemotherapy.

Ondansetron, a serotonin antagonist, is effective in controlling the emesis associated with cancer chemotherapy; however, emesis in patients receiving high-dose cisplatin is poorly controlled by ondansetron alone. Dexamethasone is an effective antiemetic with no known interaction with serotonin receptors and was thus chosen for study in combination with ondansetron. 31 patients (30 male, 1 female; median age 28.5 years, range 18-49) receiving a 4-day course of a chemotherapy regimen containing cisplatin (100-120 mg/m2) for metastatic germ-cell tumours were entered in a randomised, double-blind, cross-over trial comparing oral ondansetron plus placebo with oral ondansetron plus dexamethasone as antiemetic prophylaxis. Ondansetron (8 mg every 8 h) was given to all patients for 8 days from the start of chemotherapy. Patients were given 8 mg of dexamethasone or placebo every 8 h starting 2 h before cisplatin (on day 4) and continuing for six doses (ie, for 2 days only). A second course of chemotherapy began 14 days after the start of the first, during which patients crossed over to the alternative antiemetic regimen. Results were available from 27 patients. In the 24-48 h after cisplatin 78% of patients taking ondansetron plus dexamethasone reported complete or major control of emesis compared with 30% of those taking ondansetron plus placebo (p = 0.001). Cross-over analysis showed a significant advantage for ondansetron plus dexamethasone in the control of nausea (p = 0.013) and emesis (p less than 0.001) over the 8-day study. 24 of 26 patients expressed a preference for the combination therapy (p less than 0.001). Ondansetron plus dexamethasone is effective antiemetic prophylaxis for high-dose cisplatin chemotherapy, has few side effects, and is active when given orally.

Administration, Oral↗
PubMed1991

Cytoreductive surgery in disseminated non-seminomatous germ cell tumours of testis.

Between 1977 and 1988, 67 patients underwent surgical removal of residual metastatic deposits following an aggressive chemotherapy regimen (cisplatin, vincristine, methotrexate and bleomycin alternating with etoposide, actinomycin D and cyclophosphamide) for disseminated germ cell tumours of the testis (stage IIB or above). Ninety-one surgical procedures were performed. There were 63 (69 per cent) retroperitoneal lymph node dissections, 16 (18 per cent) thoracotomies, three (3 per cent) hepatic resections, three (3 per cent) craniotomies, five (5 per cent) delayed orchidectomies and one anterolateral decompression of the vertebral column. Nine (13 per cent) patients required a repeat retroperitoneal node dissection and one patient needed a repeat thoracotomy to remove recurrent metastatic deposits during the period of follow-up. Multivisceral resections and vascular reconstruction procedures were required in 20 (30 per cent) patients undergoing retroperitoneal node dissection. Fifty-five (82 per cent) patients remain in complete remission with a mean follow-up period of 49.6 months (range 2-121 months). Nine (13 per cent) patients died with metastatic disease between 2 months to 4 years after operation. There were three deaths in the perioperative period (4 per cent). The histology of the resected metastases revealed undifferentiated active tumour in 20 (30 per cent) patients, differentiated mature teratoma in 29 (43 per cent) patients and fibrosis/necrosis in 18 (27 per cent) patients. Twelve (60 per cent) patients with undifferentiated elements and 15 patients (60 per cent) with raised preoperative tumour markers (poor prognostic categories) are in complete remission. Cytoreductive surgery in patients with metastatic germ cell tumours offers the best chance of remission following chemotherapy even in poor prognostic group categories.

Adolescent↗
PubMed1991

Weekly etoposide, methotrexate and actinomycin D, alternating with cyclophosphamide plus vincristine (EMA/CO): a phase II study in advanced gastric carcinoma.

A total of 27 patients with measurable/evaluable metastatic or locally advanced gastric carcinoma were given combination chemotherapy comprising etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA/CO). Ten achieved partial remission, giving a response rate of 37% (95% CI; 21.7%-66.3%), 12 attained stable disease, whereas five had disease progression despite treatment. Drug toxicity was moderate to severe. Five of those who achieved partial remission underwent an attempt to resect residual disease which was successful in only three patients.

Adenocarcinoma↗
PubMed1991

Optimum management of pineal germ cell tumours.

Non-seminomatous pineal region germ cell tumours have a poor prognosis when treated with radiation alone but little is known of the results of treatment with modern chemotherapy. Between 1983 and 1990 five pineal region germ cell tumours presented to the Charing Cross Hospital, London. All five patients received the EpPlt/OMB chemotherapy schedule with escalated dose systemic methotrexate and intra-CSF methotrexate. Two patients had had prior radiotherapy. Four patients (80%) remain well and disease-free 6 months--5 years after completing therapy. Chemotherapy is an effective modality for the treatment of pineal germ cell tumours and should be used when non-seminomatous elements are present or when the placement of ventriculo-peritoneal shunt in the presence of malignant cells in the CSF presents a risk of dissemination.

Adolescent↗
PubMed1991

A phase II study of ondansetron as antiemetic prophylaxis in patients receiving carboplatin for advanced ovarian cancer. The North Thames Ovary Group.

Thirty four patients who were receiving carboplatin 400 mg/m2 for advanced epithelial ovarian cancer were treated with ondansetron antiemetic prophylaxis. Ondansetron was given as 4 mg oral +4 mg iv 30 minutes prior to carboplatin followed by 8 mg oral tds for 5 days. Of the evaluable patients complete or major control of emesis on day one was achieved in 94% of previously untreated patients and 81% of patients refractory to conventional antiemetic therapy. For the 5 day period as a whole 88% of untreated patients and 69% of those with refractory emesis reported complete or major control of nausea and vomiting. Fifteen patients noted no side effects with mild headache (30%) and constipation (21%) the most frequent problems in the remainder. Ondansetron is effective antiemetic prophylaxis for carboplatin chemotherapy and should allow the majority of these patients to be managed on an out-patient basis.

Adult↗
PubMed1991

Results with the EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) regimen in high risk gestational trophoblastic tumours, 1979 to 1989.

OBJECTIVE: To assess the efficacy, toxicity and survival in patients with high risk GTT treated with the EMA/CO regimen (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine/oncovine). DESIGN: Open non-randomized study of 148 consecutive patients referred to the Charing Cross Hospital between 1979 and 1989. SETTING: Trophoblastic disease centre in a London teaching hospital. SUBJECTS: 148 consecutive patients with high risk GTT were treated with the EMA/CO regimen. 76 patients had received no prior chemotherapy and 72 had received prior chemotherapy. MAIN OUTCOME MEASURES: Survival, causes of treatment failure and toxicity were analysed. RESULTS: Of 76 patients who had received no prior chemotherapy, 62 (82%) are in remission; an overall survival of 85% for the 148 patients. Ten of the 76 patients without prior chemotherapy died from extensive disease within 3 weeks of starting chemotherapy. The complete and partial response rates to EMA/CO chemotherapy were 80% and 18% respectively. The addition of cisplatin salvaged 9 of 11 (82%) who developed drug resistance and did not require surgery. Salvage surgery alone resulted in 7 of 8 (87%) having complete remissions. Relapse after EMA/CO chemotherapy is uncommon (5.4%) but survival is still relatively good with further chemotherapy and/or surgery with 6 (75%) of 8 patients obtaining a further sustained remission. Complications from EMA/CO chemotherapy are acceptable with myelosuppression being dose-limiting. Late sequelae are uncommon: menstruation usually returns with a few months, and no fetal abnormalities have been recorded in subsequent pregnancies. One patient developed what we presume to be a therapy-induced acute myeloid leukaemia. CONCLUSION: At present EMA/CO chemotherapy is our treatment of choice for patients with high risk GTT. Its toxicity is predictable and reversible. In patients developing drug resistance, salvage surgery is important. Future developments may include further dose intensification with the addition of haemopoietic growth factors, earlier diagnosis and the separation of gestational from non-gestational trophoblastic tumours.

Adult↗
PubMed1991

A review of the role of established tumour markers.

Increasing numbers of commercial assays for the established tumour markers are available which are capable of excellent analytical performance. Whilst all these assays are useful as research tools, their clinical value is more limited and should be appreciated before any decision is taken to offer a tumour marker assay service. 1. Calcitonin (medullary carcinoma of thyroid), alphafetoprotein (hepatoma) and human chorionic gonadotrophin (choriocarcinoma) are the only tumour markers that can be used for screening for malignancy in high risk populations. 2. Hormones, paraproteins, alphafetoprotein, human chorionic gonadotrophin and prostate specific antigen are valuable in establishing the diagnosis of certain tumour types. 3. Alphafetoprotein and human chorionic gonadotrophin concentrations at the time of diagnosis are of value in predicting prognosis in specific tumour types. 4. Although their sensitivity for a particular tumour type may be poor, most tumour markers can be used for monitoring the therapy and follow-up of selected marker positive patients. Optimal clinical results of the management of patients with malignancy are usually obtained by specialist centres, and laboratory tumour marker services should be established so that they are appropriate to local oncology specialities.

Biomarkers, Tumor↗
PubMed1990

A phase I/II study of the 5-HT3 antagonist GR38032F in the anti-emetic prophylaxis of patients receiving high-dose cisplatin chemotherapy.

A total of 24 patients who were receiving combination chemotherapy (POMB) including cisplatin at a dose of 100-120 mg/m2 were treated with the 5HT3 antagonist GR38032F (GR) as an anti-emetic prophylaxis. GR was given as a 15-min loading infusion followed by a 24-h infusion at three escalating dose levels of 1, 2 and 4 mg/h. In the first 24 h after commencing treatment, six patients had complete control of nausea and vomiting (CR), two had 1-2 emetic episodes (MR) and five had 3-5 emetic episodes (mR). The major response rate (CR + MR) was thus 35%. Eight responding patients (CR or MR) went on to receive oral GR at 8 or 12 mg t.i.d. for 5 days. In this group there was one CR, one MR, two mRs and four failures (F). There was no evidence of an improved therapeutic effect with increasing dose in either the infusion or the oral section of the study, although numbers were limited in the latter part of the trial. Toxicity was mild, with low-grade headache affecting 25% of patients being the most frequent side effect. Pharmacokinetic data was obtained in six patients at each dose level. There was a progressive rise in clearance with increasing dose, indicating that the kinetics are non-linear. However, there was no evidence of an association between high plasma levels and therapeutic efficacy. GR38032F is well tolerated and has promising single-agent activity in preventing vomiting induced by high-dose cisplatin.

Adult↗
PubMed1990

Respiratory failure due to choriocarcinoma: a study of 103 dyspneic patients.

Treatment of choriocarcinoma is mostly successful but there is still appreciable mortality from early respiratory failure. A series of 135 patients with choriocarcinoma presenting with dyspnea between 1960 and 1988 was studied to find prognostic factors for early respiratory death and to identify how mortality may be further reduced. Mortality with respect to early respiratory death (ERD) was 11% and was significantly associated with WHO prognostic score, chest X-ray appearance, central cyanosis, tachycardia, anemia, and clinical evidence of pulmonary hypertension. Indicators on chest X ray of high risk of ERD were the presence of more than 10 opacities, extensive opacification of lung fields, size of metastases, and hazy background obscuring the vascular pattern. Intensity of initial treatment was not correlated with this outcome. A set of criteria has been derived which will predict ERD with 100% sensitivity and 38% positive predictive value. These are opacification of lung fields on chest X ray of more than 50%, OR initial plasma hCG level greater than 10(5) when there is anemia and a history of chest pain. Patients presenting with choriocarcinoma and dyspnea who fulfill these criteria should be considered for extracorporeal perfusion techniques. As respiratory failure in this condition is characterized by hypoxemia and right-to-left shunting, extracorporeal perfusion should be effective. Ventilation should be avoided as no patient survived mechanical ventilation.

Adult↗