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Biomedical subjects

G J Rustin

Publications and source records attributed to G J Rustin.

At least 73 records · Page 4Linked to original sources
PubMed1995

Secondary tumours following etoposide containing therapy for germ cell cancer.

BACKGROUND: Reports have implied etoposide as the cause of secondary leukaemia in patients treated for germ cell cancer. PATIENTS AND METHODS: Between 1979 and 1992, 679 male patients with germ cell cancer received etoposide containing chemotherapy. RESULTS: Six of 679 patients developed acute myeloid leukaemia (relative risk 150; CI: 55-326). None of these patients had a primary mediastinal germ cell tumour and only 1 patient received previous radiotherapy. The median interval between the onset of cytotoxic treatment and the development of leukaemia was 27 months. The FAB M4 morphology was seen in 4 of 6 cases. CONCLUSION: The benefit of etoposide containing protocols outweigh the risk of leukaemia in patients with intermediate or high risk disease, however in patients with good risk disease non-etoposide containing protocols should be explored.

Acute Disease↗
PubMed1995

Presentation and management of choriocarcinoma after nonmolar pregnancy.

OBJECTIVE: To ascertain the mode of presentation and treatment outcome for women with choriocarcinoma after a nonmolar pregnancy. DESIGN: Retrospective analysis of case records between 1985 and 1994. SETTING: A referral centre for trophoblastic disease. SUBJECTS: One hundred women with choriocarcinoma: 62 after a live birth, six after a live birth preceded by a molar pregnancy and 32 after a nonmolar abortion. RESULTS: Choriocarcinoma after nonmolar pregnancies represent 17% of the total gestational trophoblastic tumours requiring treatment. Vaginal bleeding was the commonest symptom in all groups, but symptoms from metastatic disease were important in the group presenting after a live birth. Metastatic disease was present in 31% of cases after live birth and 43% post-abortion. The median interval between the antecedent pregnancy and choriocarcinoma was five and six months, respectively. High risk multi-agent chemotherapy was required in 82% and 60% of cases, respectively. The mortality rate was significantly higher after a live birth than a nonmolar abortion (21% vs 6%). CONCLUSIONS: Treatment of choriocarcinoma after a live birth is associated with an unacceptably high mortality rate. Vaginal bleeding is an important early symptom and a pregnancy test should be performed if it persists after usual medical treatment.

Adolescent↗
PubMed1995

Cancer Research Campaign phase II trial of temozolomide in metastatic melanoma.

PURPOSE: Sixty patients with metastatic melanoma were treated in a phase II study with the imidazotetrazine derivative temozolamide to assess further the efficacy demonstrated in previous phase I studies. PATIENTS AND METHODS: Fifty-five of 56 eligible patients were assessable for toxicity and 49 for response. The patients received temozolomide 150 mg/m2/d over 5 successive days orally (total dose, 750 mg/m2) in the first course. Courses were repeated every 4 weeks and the dose was escalated to 200 mg/m2/d x 5 (total dose, 1 g/m2) after the first course if toxicity was acceptable. Patients were all chemotherapy-naive, except for two who had previously received interferon alfa and one who had received interleukin-2 (the latter patient had also received two phase I drugs some time previously). RESULTS: A complete response (CR) was documented in three patients (all with lung metastases) and a partial response (PR) in nine patients (21% CR plus PR rate). Seven of 56 patients were not assessable for response because of early death or deterioration. The overall response rate excluding these patients is 12 of 49 (24%). The median response duration was 6 months (range, 2.5 to 22+). Toxicity of the regimen, which was mainly hematopoietic, was low. The median survival duration for all patients was 5.5 months (range, 0.5 to 29.5). For responders, the median survival duration was 14.5 months (range, 3 to 28+), with four patients still alive. CONCLUSION: Temozolomide in the schedule used has as good activity in chemotherapy-naive metastatic melanoma as the other most active agents currently in use. Further studies of the drug on its own and in combination with other agents is recommended.

Adolescent↗
PubMed1994

The long-term outcome of patients who relapse after chemotherapy for non-seminomatous germ cell tumours.

OBJECTIVE: To examine the long-term survival of a group of patients with non-seminomatous germ cell tumours, who relapse after chemotherapy and are retreated with a cisplatin and etoposide-based regimen. PATIENTS AND METHODS: At the Charing Cross Hospital between 1979 and 1988 38 patients in relapse were seen. The median interval after primary therapy was 8 months. They were treated with an intensive cisplatin and etoposide-based regimen with cycles repeated at 7-10 day intervals, and with surgery in 22 patients. RESULTS: Forty-seven per cent of patients entered a second complete remission and 88% of these remain disease free. The overall survival was 46% with a median follow-up of more than 4.3 years. Surgery was performed in 14 of 18 patients who entered a second complete remission. Adverse risk factors before initial chemotherapy and the time to relapse did not predict outcome but patients with unresectable radiological masses after relapse therapy had a poor outcome despite normalization of serum tumour markers. The tumours of 68% of patients initially treated with cisplatin-based regimens and 62% of patients who also received etoposide remained responsive to conventional doses of these drugs at relapse. CONCLUSIONS: This study demonstrates that there is a group of patients with relapsed teratoma who can be cured without the need for very high dose chemotherapy and autologous bone marrow rescue.

Adolescent↗
PubMed1993

Flavone acetic acid (FAA) with recombinant interleukin-2 (rIL-2) in advanced malignant melanoma: I. Clinical and vascular studies.

A trial of FAA and rIL-2 has been performed both to study the clinical efficacy of this combination and to determine whether they cause haemorrhagic necrosis by acting upon tumour vasculature. FAA and rIL-2 were given to 23 patients with progressing metastatic melanoma. FAA 4.8 gm m-2 was given as a 1 h infusion without urine alkalinisation on days 1, 8 and 15. rIL-2 (6-18 x 10(6) IU/m2/day) was given as a continuous infusion days 8-12 and 15-19 (nine patients) or days 8-12 only (14 patients). Treatment was repeated after 2 weeks unless there was disease progression. Of the 21 assessable patients there have been one complete (skin and liver) and two partial responses (skin and liver, skin and nodes) lasting 20 + 17 + and 15 months, overall response rate 14%. Unexpectedly severe hypotension after the third FAA, when given 2-4 days after RIL-2, was the major toxicity (8/15 grade 3 or 4). No alteration in coagulation parameters were seen during therapy of the first ten patients. No increase in tumour necrosis was seen in any of the 15 biopsies taken from ten patients after therapy. This suggests that FAA does not have similar vascular effects in human as it does in murine tumours.

Adult↗
PubMed1993

Flavone acetic acid (FAA) with recombinant interleukin-2 (rIL-2) in advanced malignant melanoma. III: Cytokine studies.

Twelve patients undergoing IL-2 and flavone acetic acid (FAA) combination immunotherapy for advanced melanoma were studied throughout treatment for the induction of measurable levels of bioactive TNF, GM-CSF and IL-6 in their serum. This was to assess the extent of secondary cytokine induction in these patients and the possible role of such cytokines in both the toxic and therapeutic responses. The nature of the treatment schedule enabled these cytokines to be measured in response to FAA alone, FAA/IL-2 and FAA alone following IL-2/FAA activation of target cells. A small rise in the serum levels of these cytokines was seen on the initial course of FAA/IL-2 but this was minor compared to the marked elevation in levels 2-8 h following the initiation of the third course of FAA given with or without IL-2 and at a time point which coincided with maximum toxicity in those patients who experienced it. These results show that FAA alone can induce cytokine release from primed target cells. This may be associated with the therapeutic effect and/or toxicity of the agent.

Adult↗
PubMed1993

Flavone acetic acid (FAA) with recombinant interleukin-2 (rIL-2) in advanced malignant melanoma. IV: Pharmacokinetics and toxicity of flavone acetic acid and its metabolites.

Flavone acetic acid (FAA) was administered at a dose of 4.8 g m-2 over 1 h to patients with advanced malignant disease in combination with Interleukin II. A new high performance liquid chromatography method is described to determine both the parent compound and eight drug-related products, and the conditions required to determine these components in plasma are discussed. The half-life over the first 8 h was 2.3 h, but the terminal clearance of the drug was extremely slow. Severe (WHO Grade 4) hypotension was observed in some patients. However, incidence of this did not appear to be associated with any differences in FAA plasma concentrations, nor were there differences in FAA clearance between those patients whose tumour responded to the drug combination and those who did not.

Antineoplastic Agents↗
PubMed1993

Molecular and biological factors in the pathogenesis of ovarian cancer.

BACKGROUND: The classic prognostic parameters are insufficient for predicting the prognosis of the individual patient. Knowledge of molecular and biological factors which are responsible for the development and progression of ovarian cancer may improve the prediction of prognosis. MATERIALS AND METHODS: Recent data both on factors associated with the development and control of ovarian cancer cells and on DNA ploidy have been reviewed. RESULTS: Observations suggest that steroid and peptide hormones have a role in disease etiology and progression, and that peptide growth factors and cytokines, oncogenes and tumor suppressor genes, by their impact on mitosis and cell number may influence the rate of mutations, which could confer malignant transformation. DNA ploidy is an objective independent prognostic factor. DNA aneuploidy indicates high risk, diploidy low risk. Only tumours shown to be DNA diploid by flow-cytometry and image cytometry are considered diploid. S-phase fraction is currently not reliable. CONCLUSION: Understanding the mechanisms involved in ovarian cancer development and growth will allow opportunities for the rational design of effective anti-tumour treatment modalities. More objective and reproducible prognostic variables will improve the predictiveness of prognosis.

DNA, Neoplasm↗
PubMed1993

Risk of cancer in relatives of patients with cutaneous melanoma.

BACKGROUND: Cutaneous malignant melanoma (CMM) is a recognized feature of the Lynch type II cancer-family syndrome and the Li-Fraumeni's syndrome. A significant contribution of these syndromes to the total burden of CMM would be reflected in an increased risk of nonmelanoma cancers in first degree relatives. METHODS: Pedigrees were taken from 85 patients with CMM using a family history questionnaire. The relative risk of death from all cancers and individual cancers in first degree relatives was calculated. RESULTS: Of the 85 questionnaires, those of 79 patients were completed and of adequate quality for analysis. The first degree relatives of CMM patients showed no increased risk of cancer death, the relative risk of cancer death being 1.0. Six patients (7.6%) had first degree relatives with CMM. One patient had a family history compatible with the dominant transmission of a predisposition to cancer. CONCLUSIONS: It is important to establish whether an increased cancer risk is present in relatives of patients with malignancies so that screening programs may be offered. This study provides little evidence to support seeing relatives for noncutaneous malignancies in the absence of a dominant family history of predisposition to cancers. The increased frequency of CMM in relatives suggests that relatives of CMM patients should be counseled on protection from the sun and examination of the skin for melanoma.

Adult↗
PubMed1993

A randomized trial comparing single-agent carboplatin with carboplatin followed by radiotherapy for advanced ovarian cancer: a North Thames Ovary Group study.

PURPOSE: To determine in a randomized trial of advanced ovarian carcinoma whether consolidation therapy with whole-abdominal radiotherapy (RT) after chemotherapy improves survival and disease-free survival compared with the continued chemotherapy. PATIENTS AND METHODS: Two hundred fifty-four patients with advanced epithelial ovarian cancer (stages IIB to IV) were entered onto a study of five monthly courses of 400 mg/m2 of carboplatin. One hundred seventeen patients with residual disease of 2 cm or less at second-look laparotomy or laparoscopy were then randomized to receive consolidation therapy, either five further courses of carboplatin at the same dosage or whole-abdominal RT (24 Gy). There was no control arm. RESULTS: Chemotherapy was well tolerated and was usually administered on an outpatient basis. Myelosuppression that was sufficient to delay chemotherapy occurred in only 3% of 1,418 courses analyzed. The main toxicity of carboplatin was nausea and vomiting, but this was easier to control than that with cisplatin. Although RT was well tolerated in the majority of the 58 patients, one patient who had been found to have multiple adhesions at second-look surgery developed fecal fistulae post-RT that resulted in the patient's death from peritonitis. Median survival for the whole group from date of surgery was 25 months. No statistical difference was found in either survival or disease-free survival between those patients who received consolidation chemotherapy and those who were treated with abdominal RT. Prognostic factors used to assess survival were stage, histology, amount of residual disease after primary surgery, and presence of tumor at second-look surgery. CONCLUSION: There seems to be no significant advantage for consolidation whole-abdominal RT compared with the continuation of the same chemotherapy in the management of advanced epithelial carcinoma of the ovary, even when no macroscopic residual disease is apparent at second-look surgery.

Adolescent↗
PubMed1993

Advanced ovarian cancer. Tumour markers.

BACKGROUND: There is a need to discover new tumour markers for ovarian carcinoma as well to delineate how the best currently available marker, CA 125 should be used. MATERIALS AND METHODS: This review examines the potential of growth factors and cytokines such as M-CSF, IL-6 and IL-10 as tumour markers as well as the over expression of oncogenes such as HER-2/neu in ovarian cancer. The major part of this review critically examines the uses of serum CA 125. RESULTS: Precise definitions for progression of ovarian carcinoma during treatment and on follow up were produced from studying a group of 71 and tested in a separate group of 164 women with ovarian carcinoma. They were found to predict progression with a false positive rate of only 8%. Definitions for response according to CA 125 are proposed. CONCLUSION: CA 125 remains the best tumour marker for ovarian carcinoma. It is not sensitive enough for screening and lack of specificity reduces its diagnostic accuracy. It's main role is in monitoring response to therapy and detecting tumour recurrence early and more reliably than by other methods.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1992

Gestational and nongestational trophoblastic tumors distinguished by DNA analysis.

In three patients in whom a diagnosis of gestational trophoblastic tumor was possible on the basis of pathology and elevated levels of serum human chorionic gonadotrophin, locus-specific minisatellite probes were used to identify restriction fragment length polymorphisms (RFLP) in DNA from the tumor, the patient, and her partner. On the basis of results from these studies, one tumor, originally diagnosed as a germ cell tumor, was reclassified as a gestational choriocarcinoma, whereas a second tumor, diagnosed as gestational choriocarcinoma, was shown to be of nongestational origin. In the third case, a diagnosis of gestational trophoblastic tumor was confirmed, but in this case the androgenetic origin of the tumor indicated that it was derived, not from the antecedent term pregnancy, but from a previous pregnancy with hydatidiform mole. This study clearly demonstrates the value of DNA analysis in the classification of tumors with trophoblastic differentiation.

Adult↗
PubMed1992

Savings obtained by CA-125 measurements during therapy for ovarian carcinoma. The North Thames Ovary Group.

The value of serial CA-125 measurements for predicting progression of ovarian carcinoma during therapy was calculated in 71 patients. The optimal algorithm that defined disease progression by CA-125 levels was either two values above 100 U/ml which had decreased by less than 50% over a minimum of 56 days, or a rise of 25% between successive samples plus a confirmatory sample. Of 13 patients with progressive disease according to the CA-125 criteria, 12 developed clinical evidence of progression within 12 months; predictions were false positive in 1, true negative in 50 and false negative in 8. Retrospective analysis showed that therapy and investigations costing 7979 pounds could have been avoided, if CA-125 assays costing 5470 pounds had been acted upon. The efficacy of the CA-125 algorithm is being independently verified to confirm that monthly CA-125 measurements whilst on treatment combine cost-effectiveness with a decrease in unpleasant interventions.

Algorithms↗
PubMed1992

Phase I study of intravenous 4-hydroxyanisole.

4-Hydroxyanisole is a depigmenting agent which has been shown to have activity against malignant melanoma when given intra-arterially in man. An intravenous dose escalation study has been carried out with the aim of obtaining maximum plasma concentrations in a 5 day schedule. 8 patients entered this study which was stopped because of drug toxicity after 3 patients had been treated at the third dose escalation of 15 g/m2. 2 patients had WHO grade 4 liver and one also grade 4 renal toxicity and another had grade 4 haemoglobin toxicity. Extrapolated plateau plasma levels between 112 and 860 mumol/l were obtained, which in vitro studies suggested would be cytotoxic. Hopefully, newer analogues will have a greater specificity for the melanin pathway with less toxicity.

Anisoles↗