PubMed Health⌕ Search

Biomedical subjects

R D Rubens

Publications and source records attributed to R D Rubens.

At least 91 records · Page 5Linked to original sources
PubMed1991

Timing of surgery during menstrual cycle and survival of premenopausal women with operable breast cancer.

Timing of operation in relation to menstrual phase might affect outlook in premenopausal women with operable breast cancer. We examined the records of 249 such women treated between 1975 and 1985, and compared overall and recurrence-free survival in those whose operation was 3-12 days after their last menstrual period (LMP) (group 1, n = 75) with those in whom it was 0-2 or 13-32 days after LMP (group 2, n = 174). Overall and recurrence-free survival were greatly reduced in group 1 women (p less than 0.001 for both). Actuarial survival at 10 years was 54% in group 1 versus 84% in group 2. This effect was independent of other factors, was of much the same importance as nodal status in multivariate analysis, was largely confined to histologically node-positive cases, seemed to be greater in women with small tumours (less than or equal to 2 cm), and was seen in patients with oestrogen-receptor positive and negative tumours. Thus phase of menstrual cycle at operation is of great importance for long-term outlook in premenopausal women with breast cancer.

Actuarial Analysis↗
PubMed1991

Comparative pharmacokinetics of doxorubicin given by three different schedules with equal dose intensity in patients with breast cancer.

The pharmacokinetics of doxorubicin given according to three different schedules with a similar dose-time intensity have been studied and compared in 16 women with metastatic breast cancer. Six patients were treated with doxorubicin 75 mg/m2 by i.v. bolus repeated every 3 weeks; 5 patients received doxorubicin by 4-day continuous infusion every 3 weeks (4 at 75 mg/m2 and 1 at 60 mg/m2); 5 patients received 25 mg/m2 by i.v. bolus given weekly. Timed blood samples were collected and plasma levels of doxorubicin and its metabolite doxorubicinol were measured by high-performance liquid chromatography with fluorescence detection. Peak plasma concentrations were measured, and areas under the concentration-time curves calculated. Peak plasma levels of doxorubicin were significantly lower with the 4-day infusion than with either of the bolus injections. The 4-day infusion, however, gave significantly greater total exposure to doxorubicin and doxorubicinol, as indicated by area under the concentration-time curve, than weekly or 3-weekly bolus treatment. A single bolus injection of doxorubicin 25 mg/m2 yielded a total exposure to doxorubicin approximately half that achieved with a 75 mg/m2 bolus injection. Over a 3-week period, therefore, total exposure to doxorubicin would be greater with the weekly low-dose schedule than with the 3-weekly administration. We conclude that drug scheduling has significant effects on doxorubicin pharmacokinetics.

Breast Neoplasms↗
PubMed1991

High-dose epirubicin as primary chemotherapy in advanced breast carcinoma: a phase II study.

A total of 40 patients with metastatic breast cancer were treated with 120 mg/m2 i.v. epirubicin every 3 weeks for a maximum of 10 cycles. Nine achieved a complete response and 17 showed a partial response, for an objective response rate of 65% (95% confidence interval, 47%-83%); the median duration of response was 7 months (range, 1-15 months) and median survival amounted to 13 months (range, 2-20 months). Leucopenia (grade 2 or 3) was seen in 14 patients on day 21 of the cycle. A subset of nine patients underwent blood counts on day 10, when all had marked neutropenia (less than 1 x 10(9)/l). Other toxicity was frequent and included nausea/vomiting (80%), alopecia (95%) and stomatitis (35%). Five patients showed a significant fall in cardiac output, but this reverted to normal after treatment. Epirubicin should have a role in the development of high-dose regimens for the treatment of advanced breast cancer.

Adult↗
PubMed1991

"Classical" CMF versus a 3-weekly intravenous CMF schedule in postmenopausal patients with advanced breast cancer. An EORTC Breast Cancer Co-operative Group Phase III Trial (10808).

The "classical" CMF (cyclophosphamide/methotrexate/5-fluorouracil) schedule was compared with a modified 3-weekly intravenous CMF schedule in postmenopausal patients with advanced breast cancer, as concern had arisen as to whether the classical schedule was the optimal way to give these drugs. The response rate with classical CMF was 48% compared with 29% for intravenous CMF (P = 0.003). Response duration was similar at 11 months, but survival longer for the classical schedule (17 versus 12 months, P = 0.016). We conclude that classical CMF is the superior regimen and attribute this to the higher dose intensity achieved.

Aged↗
PubMed1991

Iridium implant treatment without external radiotherapy for operable breast cancer: a pilot study.

A pilot study has been conducted to examine a new approach to the treatment of operable breast carcinoma. 27 patients with tumours measuring up to 4 cm in diameter have been treated by tumourectomy, axillary clearance and high dose iridium-192 implant (55 Gy) without any external beam radiotherapy. This enabled the entire local primary treatment of the breast carcinoma to be given in five days. The technique was compatible with adjuvant chemotherapy for those with involved axillary nodes. Local complications have been few and locoregional control has to date been satisfactory. With a relatively short median follow-up of 27 months, cosmesis was objectively rated as good or excellent in over 80% of cases and subjectively rated good/excellent in 96%. High dose brachytherapy now requires testing in a prospective clinical trial to determine whether it is as effective as standard breast conservation techniques for management of early breast cancer.

Adult↗
PubMed1991

Epirubicin in breast cancer patients with liver metastases and abnormal liver biochemistry: initial weekly treatment followed by rescheduling and intensification.

Fifty-two consecutive patients with breast cancer and liver metastases have been treated with epirubicin. All had a serum aspartate aminotransferase more than twice the upper limit of normal or a raised bilirubin. Initial treatment was with 6 cycles of weekly epirubicin 25 mg/m2. In patients whose liver biochemistry improved sufficiently, treatment was then changed to a 3-weekly schedule and an attempt was made to increase dose-time intensity during a further 6 cycles of epirubicin. The UICC response rate was 15/52 (29%, with 95% confidence intervals 18-42%) and median response duration was 34 weeks. All 23 patients who were eligible for rescheduling received epirubicin 3-weekly, but escalation of dose intensity was possible in only 5 patients. The activity and tolerability of weekly epirubicin has been confirmed in patients with liver metastases from breast cancer. However, late dose escalation was impracticable in the majority of patients and did not appear to improve outcome.

Adult↗
PubMed1991

Treatment of metastatic breast cancer and its complications.

Measurement of quality of life is becoming increasingly important in the evaluation of treatment for metastatic breast cancer. New approaches to endocrine treatment include use of toremifene and trilostane. The addition of fluoxymesterone to tamoxifen is reported to enhance response frequency. The relationship between dose and response for anthracycline treatment has been reaffirmed. Measurement of left ventricular ejection fraction may not be a useful predictor of clinical cardiotoxicity. The new anthracyclines, idarubicin and pirarubicin, are active in breast cancer, the former being suitable for oral administration. Several new cytotoxic drug combinations have been reported, but have no clear advantages over existing regimens. Intensification of chemotherapy facilitated by autologous bone marrow transplantation or hematopoietic growth factors is feasible; high response rates can be achieved, but with severe toxicity. This approach remains investigational and has not yet achieved an established place in routine treatment. Progress has been made in the reduction of morbidity from bone metastases by use of bisphosphonates and therapeutic isotopes.

Antibiotics, Antineoplastic↗
PubMed1990

Toxicity of intra-arterial doxorubicin in locally advanced breast cancer.

Four patients with inoperable, locally advanced breast cancer were treated i.a. with 25-35 mg/m2 doxorubicin given as a 6-h infusion on 2 successive days. In each patient, the catheter was introduced percutaneously via the femoral or brachial artery using local anaesthetic and positioned in the internal mammary artery without complications. However, within 48 h of starting treatment all four patients developed extensive erythema over the chest wall, which progressed to superficial ulceration in one case. Two patients also developed a raised hemidiaphragm and phrenic nerve paralysis that was associated with a pleural effusion in one case. This study closed prematurely because of unacceptable local toxicity; thus, we cannot assess the activity of doxorubicin given in this way. If this approach to local control is to be tested further in locally advanced breast cancer, lower doxorubicin doses should be used, or different drugs selected.

Breast Neoplasms↗
PubMed1990

Auditing palliative cancer chemotherapy.

A detailed approach to the gathering of information on the cost-effectiveness of palliative chemotherapy for patients with cancer has been described. The measures are qualitative and so difficult to study scientifically, but several innovations have been incorporated into the programme which should ensure a level of robustness to give reliable and valid information. Making judgements about the usefulness of treatment for patients involves comparing factors that are inherently incomparable and measuring those which are inherently unmeasurable. Nevertheless, it is hoped that this will be found to be a pessimistic view of what can be achieved by audit, particularly in the light of advances that have been made in assessing quality of life. At the least, the project will provide important statistical information and the existence of the audit process itself should enhance significantly standards of medical practice.

Cost-Benefit Analysis↗
PubMed1990

Proliferative activity, histological grade and benefit from adjuvant chemotherapy in node positive breast cancer.

The influence of S-phase fraction (SPF), measured by DNA flow cytometry, and histological grade on outcome following adjuvant chemotherapy was analysed for 214 patients with node positive breast cancer treated at Guy's Hospital who were entered into the Guy's/Manchester trial of combination chemotherapy with cyclophosphamide/methotrexate/5-fluorouracil (CMF) vs. no adjuvant treatment. Adjuvant CMF significantly improved relapse-free survival (RFS) for premenopausal patients whose tumours had an SPF of 10% or less (control vs. CMF, P = 0.05) and premenopausal patients whose tumours had an SPF over 10% (control vs. CMF, P = 0.003). No significant improvement in RFS attributable to CMF was seen for either subgroup of postmenopausal patients. When patients were divided into subgroups based on histological grade of tumour, an improvement in RFS attributable to CMF was seen for premenopausal patients with well differentiated (grade 1 or 2) tumours (control vs. CMF, P = 0.03) and premenopausal patients with poorly differentiated (grade 3) tumours (control vs. CMF, P = 0.006). Again, no improvement in RFS was noted for any subgroup of postmenopausal patients defined by tumour grade.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Liver metastases from breast cancer: the relationship between clinical, biochemical and pathological features and survival.

The clinical records of 312 consecutive patients with liver metastases from breast cancer were reviewed. The primary tumours were commonly poorly differentiated, although the majority were steroid receptor positive. At diagnosis of liver metastases, 60% of patients had hepatomegaly, 13% were jaundiced and 7% had ascites. A raised serum aspartate transaminase (AST) was the most common biochemical abnormality (84%), with 54% of patients having an AST of more than twice the upper limit of normal. The median survival from the time of diagnosis of liver metastases was 3.8 months. No feature existing prior to the development of liver metastases influenced subsequent survival. The presence of jaundice (P less than 0.001), ascites (P = 0.01) or hepatomegaly (P = 0.01) were all associated with a particularly poor prognosis. While any degree of elevation of bilirubin (P less than 0.001) or alkaline phosphatase (P = 0.003) was unfavourable, a raised AST alone was not predictive of shorter survival. AST only influenced survival significantly when above twice the upper limit of normal (P less than 0.001), with prognosis then progressively worsening the more elevated the level. Multivariate analysis using the Cox model suggested that the degree of elevation of AST was the single most important prognostic factor for survival after the diagnosis of liver metastases.

Aspartate Aminotransferases↗
PubMed1990

Selection of patients with breast cancer for routine follow-up bone scans.

Routine radionuclide bone scans have not been considered cost-effective for the routine follow-up after treatment of primary breast cancer. However subgroups of patients exist in whom early relapse in the skeleton is likely and this study examines again the role of the bone scan in routine follow-up. Serial radionuclide bone scans were performed every 6 months during the first 2 years of follow-up of 560 patients with breast cancer. Tumor characteristics which predict early relapse in bone were identified and the scan conversion rate from negative to positive determined for each prognostic group. A total of 199 (28%) of patients have relapsed, 50 (9%) with first recurrence in bone within two years of diagnosis. All were identified on the bone scan with a median lead time of 4 months over radiological evidence of bone involvement. The overall scan conversion rate was 2.8%. This was significantly higher in poor prognosis patients with T4 tumours (6.3%), more than four involved axillary lymph nodes (6.1%) and inoperable tumours (6.5%), than in good prognosis patients with T1 tumours (1.1%), negative axillary lymph node involvement (1.2%) or well-differentiated ductal grade tumours (1.1%). We do not recommend routine bone scans in the follow-up of all patients with breast cancer. In patients with a good prognosis after primary treatment they cannot be considered cost-effective. However, in those with features which predict early recurrence in the skeleton the frequency of scan conversion is sufficient to justify serial bone scanning during the first two years of follow-up.

Adult↗
PubMed1990

DNA index, S-phase fraction, histological grade and prognosis in breast cancer.

DNA index and S-phase fraction (SPF) were measured by flow cytometry on paraffin embedded tissue from 140 primary breast tumours. The results of DNA analysis were compared with the size, degree of axillary node involvement, histological grade and steroid receptor content of the tumours, as well as with the patients' subsequent clinical course. Forty-four (31.4%) of the 140 tumours were diploid. S-phase fraction was evaluable for 134 (95.7%). The median SPF of the whole population was 7.1%, with diploid tumours having a significantly lower median SPF (3.2%) than aneuploid (10.1%, P less than 0.001). Both aneuploidy (P = 0.002) and high SPF (P less than 0.001) were strongly associated with high histological grade. There was no significant association between either DNA ploidy or SPF and tumour size, nodal status or steroid receptor content. An SPF below the median was strongly associated with better relapse-free survival (P = 0.008), overall survival (P = 0.004) and survival after relapse (P less than 0.001). Ploidy did not correlate significantly with clinical course. Multivariate analysis using the Cox model suggested that, while SPF gave prognostic information independent of tumour size or nodal status, this independent significance was lost when histological grade was included in the analysis.

Adult↗