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Biomedical subjects

G J Rustin

Publications and source records attributed to G J Rustin.

At least 19 recordsLinked to original sources
PubMed2005

The assessment of antiangiogenic and antivascular therapies in early-stage clinical trials using magnetic resonance imaging: issues and recommendations.

Vascular and angiogenic processes provide an important target for novel cancer therapeutics. Dynamic contrast-enhanced magnetic resonance imaging is being used increasingly to noninvasively monitor the action of these therapeutics in early-stage clinical trials. This publication reports the outcome of a workshop that considered the methodology and design of magnetic resonance studies, recommending how this new tool might best be used.

Angiogenesis Inhibitors↗
PubMed2001

Use of CA-125 to define progression of ovarian cancer in patients with persistently elevated levels.

PURPOSE: To determine an accurate definition for progression of ovarian cancer in patients with a persistently elevated serum CA-125. PATIENTS AND METHODS: A retrospective analysis was performed on 300 patients with epithelial ovarian carcinoma with at least one measurement of CA-125. The date of progression according to clinical or radiologic criteria was ascertained in the 88 patients with persistently elevated CA-125 levels (> 23 U/mL). This was compared with the date of progression according to CA-125, defined as the date on which the CA-125 level first increased to >or= twice its nadir level, confirmed by a second sample also >or= twice the nadir. RESULTS: Eighty of the 88 patients had evidence of progression by both standard and CA-125 criteria, giving a sensitivity of 94%. In six of these patients, no sample was taken to confirm CA-125 doubling. In 13 patients, CA-125 doubling occurred after the date of clinical progression. Only one patient had a false-positive prediction of progression according to CA-125; the patient died as a result of a myocardial infarct before evidence of clinical progression. CONCLUSION: In patients whose CA-125 level decreases to normal after chemotherapy, a doubling from the upper limit of normal has been shown to predict progression. In those with persistently elevated levels, doubling of CA-125 from its nadir level has now been shown to accurately define progression. If confirmed, these CA-125 criteria should be used as additional end points in clinical trials.

CA-125 Antigen↗
PubMed2001

Weekly cisplatin and oral etoposide as treatment for relapsed epithelial ovarian cancer.

BACKGROUND: Response rates to chemotherapy in relapsed, platinum resistant epithelial ovarian cancer remain poor. We have explored the effectiveness of weekly cisplatin combined with prolonged oral etoposide in this patient group. PATIENTS AND METHODS: Forty-two women with relapsed, advanced ovarian cancer were treated with cisplatin 60 mg/m2 on days 1, 8, 15, 29, 36 and 43 and oral etoposide 50 mg given from day 1-14 and day 29-43. In those who were responding and tolerating treatment (n = 13) oral etoposide 50 mg was continued for two further cycles (days 1-21 repeated every 28 days). The interval since last platinum containing chemotherapy was > 6 months in 28 patients and < 6 months in 16 patients. RESULTS: Thirty-six patients were evaluable for response according to CA 125 criteria giving an overall response rate of 44%. The response rate in evaluable patients declined with increasing numbers of previous treatments: 57% with one prior treatment, 42% with two, 40% with three or more. The response rate in patients who had received platinum chemotherapy within six months prior to treatment was 46%. The only significant non-haematological toxicity was nausea and vomiting in 4 patients who experienced greater than grade 2 toxicity. The number of patients experiencing haematological toxicity more than grade 2 was as follows: haemoglobin 3, white blood count 12, platelets 6. Sixteen patients had dose delays and two had dose reductions. CONCLUSION: We conclude that this short but intensive regimen provides worthwhile response rates, even in those patients who would ordinarily be considered refractory to platinum, and has an acceptable toxicity profile.

Adenocarcinoma, Clear Cell↗
PubMed2000

Surveillance for stage I testicular germ cell tumours: results and cost benefit analysis of management options.

Between 1979 and 1996 303 men with stage I testicular germ cell tumours (120 seminoma and 183 non-seminomatous germ cell tumours (NSGCT)) were enrolled onto a programme of surveillance. In our institutions the frequency of computed tomography (CT) scans is reduced compared with other centres. For all 303 men, the median follow-up is 5.1 years (range: 0.1-21.7 years) and there have only been 3 deaths (1 from disease, 1 from neutropenic sepsis and 1 from secondary leukaemia). 52/183 (28%) patients with NSGCT and 18/120 (15%) patients with seminoma have relapsed. The relapse-free survival at 5 years is 82% for seminoma and 69% for NSGCT (Logrank P=0.004). All men who relapsed, except 1 man with NSGCT, were in the International Germ Cell Cancer Collaborative Group good or intermediate prognosis group at relapse. Half of the seminoma relapses presented with symptoms and 31% of the NSGCT relapses. The remaining relapses were detected serologically or radiologically by the surveillance programme. 5 men (2%) on surveillance, 3 with initial diagnosis of seminoma and 2 with NSGCT, have developed second contralateral testis tumours (all stage I seminomas). In a well motivated centre a policy of surveillance for stage I testicular germ cell tumours (both NSGCT and seminoma) is associated with a low mortality rate (3/303, 1%) and may have the advantage of sparing overtreatment with potentially toxic therapies in this group of young men.

Adolescent↗
PubMed2000

Diagnostic delay and risk of relapse in patients with stage I nonseminomatous germ cell tumour followed on active surveillance.

OBJECTIVE: To determine whether delayed diagnosis affects the outcome of patients with stage I nonseminomatous germ cell tumour (NSGCT) followed by a policy of 'active surveillance'. PATIENTS AND METHODS: A series of 185 consecutive patients with either low-risk (no vascular invasion) or unknown risk stage I NSGCT referred to Mount Vernon Hospital between 1983 and 1998 were analysed retrospectively for the type and duration of symptoms before orchidectomy, time to relapse, and for site and stage of relapse. RESULTS: Twenty-six patients (14%) relapsed within a medium follow-up of 98 months. The median (range) time to relapse was 4 (1-14) months. All patients were effectively salvaged with chemotherapy and in some by surgery. The median duration of symptoms before orchidectomy for those patients relapsing was 2 months, and not significantly different from those who did not relapse. CONCLUSIONS: In patients with stage I NSGCT the duration of symptoms before diagnosis did not influence the probability of relapse.

Adolescent↗
PubMed2000

Role of tumour markers in monitoring epithelial ovarian cancer.

Currently the only tumour marker to have a well-defined and validated role in the management of ovarian cancer is CA125. Changes in the level of CA125 can be used as a reliable indication of response or progression according to various criteria, but it does not yet have a clear place in diagnosis or prognosis. Its value as part of a screening tool and during routine follow-up remain the subject of ongoing trials. Other markers remain experimental and do not have a well-defined contribution to make at present.

Biomarkers, Tumor↗
PubMed2000

Long-term follow-up of residual masses after chemotherapy in patients with non-seminomatous germ cell tumours.

This retrospective study was undertaken to determine the outcome of patients with non-seminomatous germ cell tumour who achieved a serological complete response but who had residual radiologic abnormalities upon completion of primary platinum-based chemotherapy. This was an analysis of 76 consecutive patients treated at Mount Vernon Hospital between 1983 and 1997. The patients were placed into two groups based upon whether they had surgical resection (surgery group, 48 patients) or observation (observation group, 28 patients) of residual radiologic masses on completion of initial chemotherapy (to enter the surgery group, complete surgical resection must have been achieved). The primary end-points were progression-free and overall survival. The percentage of patients alive with median follow-up 66 months was 90% for the surgery group and 80% for the observation group (P = 0.53, not significant). The percentage of patients continuously disease-free was 70% in the surgery group and 80% in the observation group (P = 0.31, not significant). In the small sub-group of patients with differentiated teratoma (TD) in the primary lesion who were observed, there was no excess risk of relapse or death. Patients who achieve a serological complete response after primary chemotherapy, but are left with </= 2 cm radiological masses that are not cystic and have responded, can be safely observed with diligent follow-up.

Adolescent↗
PubMed2000

Biological variation and analytical imprecision of CA 125 in patients with ovarian cancer.

Despite the availability of serial data on CA 125 in ovarian cancer, the problem of interpreting a change over time is still unsolved. Changes in marker concentrations are due not only to patients improving or deteriorating but also to analytical imprecision and normal intra-individual biological variation. The aim of this study was to assess the analytical imprecision (CV(A)) and the intra- and inter-individual biological variation (CV(I) and CV(G), respectively) of CA 125 in a group of 26 patients with clinically stable ovarian cancer. Furthermore, the critical difference for a change between two consecutive CA 125 concentrations calculated as square root(2) x Z x (CV(A)2 + CV(I)2)(1/2) (Z =1.65 for unidirectional and 1.96 for bidirectional changes, p < or = 0.05) and the index of individuality calculated as ((CV(A)2+CV(I)2)/CV(G)2)(1/2) were estimated. After the exclusion of outliers, CV(A) and the average CV(I) and CV(G) were 12.1%, 24.0%, and 43.1%, respectively. The index of individuality was 0.62 and the critical difference calculated for unidirectional changes was 62.6%. CV(A) and CV(I) contribute considerably to the variation in serial results and should, therefore, be included in the criteria for serum tumor marker assessment during monitoring of patients with ovarian cancer. The cut-off value of CA 125 is of minor value in detecting unusual results for an individual subject, when previous measurements from an individual are available. These measurements should be preferred as reference for interpretation of new results.

Biomarkers, Tumor↗
PubMed2000

Etoposide and cisplatin/etoposide, methotrexate, and actinomycin D (EMA) chemotherapy for patients with high-risk gestational trophoblastic tumors refractory to EMA/cyclophosphamide and vincristine chemotherapy and patients presenting with metastatic placental site trophoblastic tumors.

PURPOSE: To evaluate the results of etoposide, cisplatin/etoposide, methotrexate, and actinomycin D (EP/EMA) chemotherapy in patients with gestational trophoblastic tumors (GTTs), who have relapsed after or who have become refractory to EMA/cyclophosphamide and vincristine (CO) chemotherapy, and in patients presenting with metastatic placental site trophoblastic tumors (PSTTs). PATIENTS AND METHODS: We have treated a total of 34 patients with GTT and eight patients with metastatic PSTT with the EP/EMA chemotherapy schedule. RESULTS: Twenty-two patients received EP/EMA because of apparent drug resistance to EMA/CO, and because the human chorionic gonadotropin (hCG) was near normal, they were not assessable for response. Twenty-one of these patients (95%) are alive and in remission. In the group where the hCG was high enough to confirm a response (greater than one log fall in hCG) to EP/EMA, all 12 patients responded and nine of these patients (75%) are alive and in remission. We have treated three patients with PSTT where the interval from antecedent pregnancy was less than 2 years, and all patients (100%) are alive and in remission. We have treated five patients where the interval from antecedent pregnancy was greater than 2 years and one fifth (20%) remain in remission. The survival for patients with GTT is 30 (88%) out of 34 patients and four (50%) out of eight patients for PSTT, giving an overall survival for these two cohorts of 34 (81%) out of 42 patients. The toxicity of this schedule is significant, with grade 3 or 4 toxicity (National Cancer Institute common toxicity criteria) recorded in hemoglobin (21%), WBC (68%), and platelets (40%). The role of surgery in this group of patients is important and contributed to sustained remission in five patients (23%) and possibly helped an additional seven patients (32%). CONCLUSION: EP/EMA is an effective but moderately toxic regimen for patients with high-risk GTT who become refractory to or relapse from EMA/CO chemotherapy. Also, EP/EMA clearly has activity in patients with metastatic PSTT.

Adolescent↗
PubMed2000

Selection of active drugs for ovarian cancer based on CA-125 and standard response rates in phase II trials.

PURPOSE: To determine whether precise definitions of response based on serial CA-125 levels can predict the activity of drugs in phase II trials for ovarian cancer as accurately as standard criteria. PATIENTS AND METHODS: Fourteen different drugs for relapsed ovarian cancer were analyzed in 25 treatment groups in 19 clinical trials. Response rates were estimated in 1,457 assessable patients according to standard criteria and in 1,092 assessable patients according to CA-125. For each drug trial, the observed response rates acted as the input data for an evaluation of how the two criteria would perform in a hypothetical Gehan two-stage phase II trial, accepting a target drug efficacy rate of 20% and a rejection error of 5%. RESULTS: CA-125 and clinical response criteria were concordant in 20 of the 25 groups, with less than 5% chance of rejecting the drug in nine groups and greater than 5% in 11 groups. In four groups, the drug had less than 5% chance of being rejected by CA-125 but greater than 5% chance of being rejected by standard criteria. The difference in the classification of drugs by the standard and CA-125 response criteria was not statistically significant (P =.38, McNemar's test). CA-125 response rates were slightly higher than standard response rates by a factor of 1.11. CONCLUSION: Definitions based on a 50% or 75% decrease of CA-125 levels accurately predicted which drugs in phase II trials for relapsed ovarian cancer were active and justified further investigation.

Antineoplastic Agents↗
PubMed1999

Outcome of epithelial ovarian cancer in women under 40 years of age treated with platinum-based chemotherapy.

We retrospectively investigated the outcome of ovarian cancer in women aged less than 40 years treated in three randomised phase III studies of platinum-based chemotherapy. 624 patients had invasive epithelial ovarian cancer. A Cox proportional hazard model was used to study prognostic variables. 29 women (5%) were under 40 years of age. Stage, histological grade and amount of residual disease were significantly worse in women aged > or = 40 years. Median follow-up was 66.7 months. At 5 years 65% of women below 40 years of age were alive compared with 20% of older women (95% confidence interval (CI) of the difference 27.1-63.0). The progression-free interval was 59% versus 16% (95% CI 24.3-60.8). No patient under 40 years of age relapsed after 18 months. Age > or = 40 years was a poor prognostic variable, particularly for serous tumours, the commonest subtype in younger women (hazard ratio (HR): 3.33). Other prognostic factors were Eastern Cooperative Oncology Group (ECOG) performance status (HR: 1.25), presence of residual disease (HR: 1.43), histological grade (HR: 1.36) and International Federation of Gynaecology and Obstetrics (FIGO) stage (HR: 1.47). These results suggest that there are biological differences in the behaviour of serous carcinoma of the ovary in women of reproductive age compared with older women.

Adolescent↗
PubMed1999

Advanced epithelial ovarian cancer: 1998 consensus statements.

BACKGROUND: During an international workshop held in September 1998, a group of specialists in the field of ovarian cancer reached consensus on a number of issues with implications for standard practice and for research of advanced epithelial ovarian cancer. METHODS: Five groups of experts considered several issues which included: biologic factors, prognostic factors, surgery, initial chemotherapy, second-line treatment, the use of CA 125, investigational drugs, intra-peritoneal treatment and high-dose chemotherapy. The group attempted to arrive at answers to questions such as: Are there prognostic factors, which help to identify patients who will not do well with current therapy? What is the current best therapy for advanced ovarian carcinoma? What directions should research take in advanced ovarian cancer? These issues were discussed in a plenary meeting. RESULTS: One of the major conclusions drawn by the consensus committee was that in previously untreated advanced ovarian cancer, cisplatin plus paclitaxel has been shown to be superior to previous standard therapy with cisplatin plus cyclophosphamide (level I evidence). However, for many patients, carboplatin plus paclitaxel is a reasonable alternative because of toxicity and convenience considerations. Most participants felt that the benefits in terms of toxicity for the paclitaxel-carboplatin are such that its widespread adoption at this stage is justified. Until mature survival data are available a minority of investigators would recommend continued use of cisplatin plus paclitaxel, specifically for those patients with advanced disease with the best prognostic characteristics. For future clinical research in this area, new end points for randomised clinical trials, together with a new Trials Network, are proposed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Use of tumour markers in monitoring the course of ovarian cancer.

BACKGROUND: There is a need to delineate how the best available serum marker for ovarian cancer, CA 125 should be used in monitoring the treatment of individual patients, and in clinical trials. PATIENTS AND METHODS: The situations where measurement of CA 125 could alter the management of individual patients during therapy and at relapse were critically analysed. Precise definitions for response according to CA 125 were first developed and tested on 989 patients receiving first line therapy and have since been tested on over 2000 patients in phase 2 trials. Precise definitions for progression were developed from 71 patients during and on 255 patients both during and after initial chemotherapy. RESULTS: In individual patient management, progression on initial chemotherapy can be demonstrated by serial rise in CA 125 suggesting the need for a change in therapy. A confirmed doubling of CA 125 from the upper limit of normal during follow up accurately predicts relapse. This endpoint needs prospective testing for use in clinical trials. Precise definitions of response based on a 50% or 75% fall in CA 125 levels accurately predicts whether a cytotoxic agent is active against ovarian cancer. CONCLUSION: Precise definitions of response based on CA 125 should be used in phase 2 trials of new cytotoxic drugs.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

How long should first-line chemotherapy continue?

Documentation for the optimal duration of first-line chemotherapy in advanced ovarian cancer is limited. Three randomised trials have compared 5-6 cycles with 8, 10 and 12 cycles respectively. None of the studies showed benefit of chemotherapy beyond 6 cycles. At the moment the standard number of cycles therefore must be 6 cycles. However, these data are based on platinum poly-chemotherapy regimens without taxanes. It may be that the optimal number of cycles is different when using taxanes regimens. It is not possible to tell from the literature if there is a relationship between the number of cycles and response or between the cumulative dose and response. At the moment no trial has shown any benefit of high-dose intensity chemotherapy administered over a short time compared with standard dose chemotherapy administered over a longer period.

Antineoplastic Agents, Phytogenic↗