Randomized trial comparing aminoglutethimide with high-dose medroxyprogesterone acetate in therapy for advanced breast carcinoma.

A total of 218 postmenopausal patients were entered in a prospective randomized trial comparing aminoglutethimide (AG) and high-dose medroxyprogesterone acetate (MPA) as second-line hormonal therapy for advanced breast carcinoma. All responses were assessed by the criteria of the International Union Against Cancer. The response rates were 27% (29 of 106 patients) for AG and 31% (35 of 112) for MPA, but if stabilization of previously progressive disease is included, then the overall response rates were 51% (54 of 106) and 54% (61 of 112) for patients receiving AG or MPA, respectively. There was no difference in response to the two drugs at any site of disease, and the durations of response and survival were identical for the two drugs. The time to response was significantly shorter for patients treated with MPA (median, 8.7 wk) than for those treated with AG (median, 15.3 wk) (chi 2 = 9.96, 1 df, P = .0016). The percentage of patients experiencing toxic effects was equivalent in both arms, although the patterns and time courses of these effects were different.

A report of the consensus workshop panel on the treatment of brain metastases.

The consensus workshop on management of brain metastases focused on several broad issues concerning the patient with brain metastases. These issues included: What are the goals of treatment? Who should not be treated with radiation? What are the optimal treatment regimens? What are the areas of controversy where future investigations may be useful? The brain consensus panel attempted to develop guidelines for radiation oncologists through use of a decision tree format. Existing data to support management decisions, particularly those regarding radiation treatment, were reviewed. Data regarding cost of treatment as well as data regarding explicit quality of life measures were felt to be very important but were largely not available and therefore played little scientific role in the guideline development. Areas where controversy existed and where consensus could not be reached were identified.

A randomized trial of intracavitary bleomycin and Corynebacterium parvum in the control of malignant pleural effusions.

Fifty-eight patients with malignant pleural effusions were entered into a prospectively randomized clinical trial comparing the efficacy of a local instillation of bleomycin or corynebacterium parvum (C. parvum) in controlling fluid reaccumulation after simple needle aspiration (thoracentesis). The response was assessed at 30 days by chest X-ray and clinical examination. There were 44 evaluable patients; 18 of 25 (72%) of those receiving bleomycin and 9/19 (47%) of those who had C. parvum gained a complete or partial response. This difference in response rate was not statistically significant (p = 0.13). The majority of patients had an effusion from a primary breast carcinoma and the response in this group was almost statistically significant (p = 0.06) with 74% of bleomycin patients and 43% of C. parvum patients responding. Fever following instillation was more common with C. parvum (53% of patients compared with 24% after bleomycin, p = 0.02), whereas nausea was more common after bleomycin (28% vs. 10.5%, p = 0.16). Local chest pain after aspiration occurred in 52% of the bleomycin group and 47% of the C. parvum subjects. There was no significant difference between the groups in age, sex, tumour type, presenting symptoms, volume of aspirate, systemic therapy or number of previous aspirations. Both of these agents appeared to be active in the control of malignant pleural effusions although the response rate was higher with bleomycin and overall, both have acceptable levels of toxicity.

A phase II study of oral idarubicin (4-demethoxydaunorubicin) in advanced breast cancer.

Idarubicin (4-demethoxydaunorubicin: DMDNR) is an orally active analogue of daunorubicin that has shown promising activity in animal and early clinical studies. We gave idarubicin in a phase II study to patients with advanced breast cancer unresponsive to hormonal manipulation and in some cases to standard chemotherapeutic agents. Idarubicin was given orally every 21 days at a starting dose of 40 mg/m2 with dose escalation until myelosuppression occurred. Nadir blood counts showed that patient compliance was good. Of 33 patients studied, 32 are evaluable for response: 4 (13%) had partial responses (95% confidence interval 1%-23%) with a duration of response between 32 and 59 weeks; 8 (25%) had static disease for between 17 and 48 weeks; and 20 failed to respond. For patients not previously exposed to chemotherapy, the response rate was 3/19 (16%). Toxicity was mild, with little or no gastro-intestinal disturbance in the majority of patients, no severe haematological toxicity and little alopecia. Two patients however, were withdrawn from the study because of toxicity; one with a skin rash and one with severe vomiting. Idarubicin produces little toxicity when given orally at a dose of 40 mg/m2 every 21 days, but its activity in breast cancer is insufficient to justify its further use with this schedule. Further studies should be undertaken only if direct comparison can be made with doxorubicin.

Rectal carcinoma: a new technique to allow safer postoperative irradiation of the pelvis.

Local recurrence after abdomino-perineal excision of the rectum for Dukes C carcinoma is common. The influence of postoperative radiotherapy in reducing this is currently under investigation, and one of the potential complications is radiation damage to the small bowel. This paper describes a simple and quick method of excluding the small bowel from the pelvis which, combined with more sophisticated radiation field planning, could dramatically reduce the incidence of enteric effects.

A prospective randomized double-blind trial comparing ondansetron versus prochlorperazine for the prevention of nausea and vomiting in patients undergoing fractionated radiotherapy.

In a multicentre, international double-blind trial, patients undergoing courses of five or more daily radiotherapy treatments to the upper abdomen were randomized to receive either oral ondansetron 8 mg t.d.s. or oral prochlorperazine 10 mg t.d.s. throughout their radiation course in order to try to prevent nausea and vomiting. A total of 192 patients were recruited, 135 of whom were included in the efficacy analysis; of these, 70 received ondansetron and 65 prochlorperazine. Forty-three (61%) of the patients prescribed ondansetron and 23 (35%) of those given prochlorperazine had a complete response, with no emetic episodes throughout their treatment course (P = 0.002). There was, however, no significant difference between the two groups with respect to the incidence and severity of nausea. Seventeen (24%) of the patients on ondansetron and 19 (29%) of those given prochlorperazine were treatment failures, experiencing more than five emetic episodes on their worst day during the study. Both drugs were well tolerated, although constipation was seen more commonly with ondansetron.

The quality of life of early breast cancer patients treated by two different radiotherapy regimens.

A cohort of 63 patients participating in a prospectively randomized trial evaluating two different radiotherapy regimens and adjuvant tamoxifen in the conservative management of early breast cancer were monitored by a series of psychological measures. The aim was to determine whether there was any difference between the radiotherapy schedules in terms of their impact on the patient's quality of life and whether measures of coping style and trait anxiety could be used to predict the subjective response to treatment. Overall, radiotherapy had little effect on quality of life and the differences between the two regimens were minor with significantly more of those women on the longer treatment schedule experiencing a transient weight change, disruption of private life and loss of positivity compared with those on the shorter schedule. In anticipating psychological adjustment to treatment, coping style proved unhelpful but trait anxiety was found to be a robust indicator of response, suggesting that it may be possible to determine in advance those patients who are likely to exhibit psychological distress during radiotherapy.

A phase II evaluation of human lymphoblastoid interferon (Wellferon) in relapsed high grade malignant glioma. Medical Research Council Brain Tumour Working Party.

During the 1980s a number of studies suggested there might be a role for interferon in the treatment of high grade gliomas. In the light of these reports a formal Phase II evaluation of human lymphoblastoid interferon (Wellferon) was undertaken in patients with high grade gliomas which had relapsed after conventional radiotherapy; 14 patients were treated and no objective clinical responses were seen. This indicates that the overall response rate to interferon therapy in this situation would be less than 20%. It is therefore concluded that interferon administration is unlikely to be of value in the management of relapsed high grade gliomas.

Clinical oncology services to district general hospitals: report of a working party of the Royal College of Radiologists.

We conducted a survey of multidisciplinary non-surgical cancer services in district general hospitals without departments of radiotherapy and oncology. All consultants in clinical oncology (radiotherapy and oncology) in the United Kingdom were sent a questionnaire. This report is based on the analysis of information on 235 district general hospitals, which have an average of 450 acute or general beds. Non-surgical medical care for cancer patients at these hospitals is mainly provided by consultants in clinical oncology based at cancer centres. Initial assessment and follow-up, and some investigations and drug treatment, are organized at the district general hospitals, but radiotherapy and a substantial proportion of cytotoxic chemotherapy is administered at the cancer centres. The principal finding of the survey is that the average total weekly commitment of consultants in clinical oncology at district general hospitals is just under two sessions. We estimate that for each session at present provided at these hospitals there are five new cancer patients who would benefit from a specialized oncological opinion. For each new patient consultation there is a need for 5-10 times as many follow-up consultations. It is clear that the time available for cancer patients at district general hospitals, which on average are 22 miles away from the cancer centres, is far from adequate. We believe that it is correct to continue to base cancer services at cancer centres. This helps to ensure the maintenance of high standards and continuity of care. There is no need to alter the system, but there is a need to increase substantially specialist oncological presence at district general hospitals through the appointment of additional visiting consultants.

Lymphoma of the prostate treated with radiotherapy.

Primary prostatic lymphoma is a rare disease. We report a 73-year-old man who initially presented with features of bladder outflow obstruction. Histology revealed non-Hodgkin's lymphoma. He was treated with radical radiotherapy with complete regression of disease. Although the follow-up period is, as yet, relatively short, the apparently good result in this patient supports the view of other recent reports that the outcome in this situation depends on the features of the individual disease rather than it being universally poor as had been previously suggested.

Final results of the Royal College of Radiologists' trial comparing two different radiotherapy schedules in the treatment of cerebral metastases.

Between February 1990 and February 1993, 25 centres in the UK recruited 544 patients into a prospective randomized trial comparing two whole-brain radiotherapy regimens (30 Gy in ten fractions over 2 weeks versus 12 Gy in two fractions on consecutive days) for the treatment of patients with symptomatic cerebral metastases. Of these patients 533 were eligible for analysis: 270 assigned to the two-fraction arm and 263 to the ten-fraction arm. The two groups were well balanced with respect to patient characteristics. Median survival was 77 days with two fractions (95% CI 68-89) and 84 days for the longer schedule (95% CI 67-102). Analysis of the survival curves showed a marginal advantage for ten fractions (P = 0.04). Performance status (P = 0.0001), site of primary tumour (P = 0.006), dose of dexamethasone (P = 0.004), age (P = 0.04) and randomization treatment (P = 0.03) were independant factors associated with survival. The classification of patients into good or poor risk groups based on these factors, excluding treatment, showed highly significant differences in survival (P < 0.0001). Predictive models suggested that any benefit attributable to the longer radiotherapy schedule was confined to those in a good prognostic group (these patients formed 22% of the study population). Radiation related side effects, other than alopecia, were seen in 12% of patients receiving two fractions and 8% of those given ten fractions. The short survival of many patients hampered the assessment of response, but overall responses were seen in 39% of those given two fractions and 44% of patients receiving ten fractions. These results suggest that any increase in survival due to longer radiotherapy treatment is confined to good prognosis patients, but, for the majority, there is no advantage and the value of radiotherapy for these patients relates purely to the possibility of control or relief of distressing symptoms.

A prospective randomized trial to evaluate different oral dose regimens of medroxyprogesterone acetate in women with advanced breast cancer.

A prospective randomized study was conducted to try to answer two questions: is a loading dose of medroxyprogesterone acetate (1000 mg p.o. q.d.s. for 48 h) superior to conventional dosing; and does an oral maintenance dose of 1000 mg daily offer any advantage over 500 mg daily in women with advanced breast cancer who have failed to respond to, or have relapsed after, tamoxifen? Of 211 patients randomized, 207 were evaluable. There was no improvement in response rates, time to response, response duration or overall survival as a result of the loading dose. When comparing high and low maintenance doses, there was a significant difference in response rates (48% versus 32%; chi 2 = 10.09, df = 2, P = 0.006) and survival (66% versus 41% alive at 12 months; chi 2 = 9.06, df = 1, P = 0.003) in favour of the higher dose regimen, although there was no significant difference in the duration of response. There was no additional toxicity attributable to the loading dose regimen, but side effects were more frequent with the high dose maintenance schedule (141 of 201 adverse effects occurring in these two groups) although the incidence of severe toxicity was similar with both high dose and low dose treatments.

Results of a randomized, double-blind comparative study of ondansetron and metoclopramide in the prevention of nausea and vomiting following high-dose upper abdominal irradiation.

Ondansetron is a 5-hydroxytryptamine 3-receptor antagonist which has shown activity in the prevention of cytotoxic-induced emesis. Preliminary non-randomized studies also indicated efficacy in preventing sickness following radiotherapy. The present study was therefore undertaken to compare the efficacy and safety of ondansetron (8 mg tds orally) and metoclopramide (10 mg tds orally) in preventing sickness after single-exposure radiotherapy treatments of 8-10 Gy to the upper abdomen. Of 82 evaluable patients 38 received ondansetron and 44 metoclopramide. On the first day after irradiation vomiting or retching was prevented in all but one of the patients on ondansetron whereas metoclopramide achieved complete control of these symptoms in only 46% of subjects (P less than 0.001). Similarly nausea was significantly better controlled by ondansetron in the first 24 hours after treatment (P = 0.001). Complete or major control of vomiting or retching was maintained for 92%-100% of patients on ondansetron during the five days of the study period. In the metoclopramide group the proportion of patients with equivalent control improved from 70% on day 1 to 95 on day 5. Both drugs were well-tolerated.

Radiotherapy for pain relief in locally recurrent colorectal cancer.

Eighteen patients with local recurrence of colorectal cancer have been treated by external beam radiotherapy for pain relief. Seven received a fractionated course of 4500cGy and the remainder received single fractions of 1000cGy, a number being treated more than once. The median survival for all patients once recurrence had produced pain was 7 months. Treatment benefit was recorded in 71% treated by fractionated courses and in 66% by single fractions. The duration of pain relief was 3 months for each method. The repeatability of single fraction treatment indicates that this is a worthwhile alternative technique, particularly for those in poor general condition.