A randomized trial of cisplatin versus cisplatin plus methotrexate in advanced cancer of the urothelial tract.

One hundred eight patients with recurrent or metastatic transitional cell carcinoma of the urothelial tract were randomized to receive cisplatin (C) 80 mg/m2 on day 1 every 4 weeks, or methotrexate (M) 50 mg/m2 on days 1 and 15 plus C 80 mg/m2 on day 2 every 4 weeks (C + M). Fifty-three eligible patients were randomized to C + M and 55 to C. In the C + M arm, 45% of patients responded (complete response [CR], 9%) and 31% (CR, 9%) in the C arm (P = .18). In the C arm, 20 patients failing or relapsing after C received M. Two patients responded, and four with progressive disease (PD) and one with a previous partial response (PR) showed no change. The median survival was 8.7 months (C + M arm) and 7.2 months (C arm), P = .7. Relapse-free survival was not significantly different, but C + M was associated with a significantly increased time to disease progression (median, 5.0 months, v 2.8 months for C arm). The response of untreated patients (37%) was not different from those with prior treatment (39%). On the C + M arm, 92% of patients and 96% of patients on the C arm received 85% or more of the scheduled C dose. Significantly more grade 3 or 4 hematological toxicity (27% v 2%; P = .01) and mucositis (20% v 0%; P = .0005) occurred in patients on the C + M arm. Although the initial response rates seen on the combination arm look superior, and the time to disease progression is increased, these effects have not translated into a clinically important increase in the duration of survival and were associated with increased toxicity.

Management of hormone-resistant prostate cancer: an Australian trial.

The management of metastatic prostate cancer that has relapsed after initial hormonal manipulation remains a major problem, with the majority of patients dying within 12 months. Their clinical course is frequently characterized by progressive debilitation, pain, and other tumor-related symptoms. A phase II, non-randomized multicenter clinical trial was carried out in Australia in 1985-1986 to assess the efficacy and toxicity of mitoxantrone. Substantial anticancer activity was shown against hormone-refractory prostate cancer, indicated by reduction in tumor-related symptoms, improvement in quality of life indices, and a median survival of 10 months in patients with a heavy tumor burden. Although it is not possible to equate this nonrandomized series more fully with current experience since routine prostate-specific antigen measurement was not performed, the median survival of 10 months was equivalent to or better than the survival times reported from most other institutional reports of the time. Even more importantly, however, major improvements were noted in such subjective indices as reduction in pain, weight gain, and performance status. Toxicity was also acceptable, with the major side effect being asymptomatic myelosuppression.

A randomised controlled trial of a consumer-focused e-health strategy for cardiovascular risk management in primary care: the Consumer Navigation of Electronic Cardiovascular Tools (CONNECT) study protocol.

INTRODUCTION: Fewer than half of all people at highest risk of a cardiovascular event are receiving and adhering to best practice recommendations to lower their risk. In this project, we examine the role of an e-health-assisted consumer-focused strategy as a means of overcoming these gaps between evidence and practice. Consumer Navigation of Electronic Cardiovascular Tools (CONNECT) aims to test whether a consumer-focused e-health strategy provided to Aboriginal and Torres Strait Islander and non-indigenous adults, recruited through primary care, at moderate-to-high risk of a cardiovascular disease event will improve risk factor control when compared with usual care. METHODS AND ANALYSIS: Randomised controlled trial of 2000 participants with an average of 18 months of follow-up to evaluate the effectiveness of an integrated consumer-directed e-health portal on cardiovascular risk compared with usual care in patients with cardiovascular disease or who are at moderate-to-high cardiovascular disease risk. The trial will be augmented by formal economic and process evaluations to assess acceptability, equity and cost-effectiveness of the intervention. The intervention group will participate in a consumer-directed e-health strategy for cardiovascular risk management. The programme is electronically integrated with the primary care provider's software and will include interactive smart phone and Internet platforms. The primary outcome is a composite endpoint of the proportion of people meeting the Australian guideline-recommended blood pressure (BP) and cholesterol targets. Secondary outcomes include change in mean BP and fasting cholesterol levels, proportion meeting BP and cholesterol targets separately, self-efficacy, health literacy, self-reported point prevalence abstinence in smoking, body mass index and waist circumference, self-reported physical activity and self-reported medication adherence. ETHICS AND DISSEMINATION: Primary ethics approval was received from the University of Sydney Human Research Ethics Committee and the Aboriginal Health and Medical Research Council. Results will be disseminated via the usual scientific forums including peer-reviewed publications and presentations at international conferences CLINICAL TRIALS REGISTRATION NUMBER: ACTRN12613000715774.

Aminoglutethimide in advanced prostatic carcinoma.

We have treated 34 patients with advanced prostate cancer, resistant to orchiectomy or oestrogen therapy, with aminoglutethimide. Seven patients (21%) showed improvement in pain and performance status for prolonged periods. By NPCP criteria six patients had stable disease and one had partial tumour response. Six of these patients remained on oestrogen therapy. Suppressed gonadotrophin levels (FSH and LH), despite orchiectomy, correlated strongly with benefit from aminoglutethimide. No relationships between response to treatment and changes in serum testosterone, dehydroepiandrosterone, oestradiol or prolactin were found. Six patients had side effects requiring cessation of therapy. A further 27 patients developed less severe toxicity. Despite its toxicity, these results show that aminoglutethimide has a role in the management of advanced prostatic cancer resistant to primary hormonal manipulation.

Intravenous cis-platinum for invasive bladder cancer. Safety and feasibility of a new approach.

The five-year survival rate of patients with locally invasive bladder cancer (stages T3-T4, Nx, Mo) is less than 50% whatever treatment is given. In an effort to improve the prognosis of patients with this disease, we have incorporated into a management protocol two cycles of intravenous administration of cis-platinum before surgery or radiotherapy (which function as the "definitive" treatment). In 10 of the first 12 patients treated, tumour necrosis has been demonstrated histologically, and definite clinical responses have been observed in eight patients after two cycles of cis-platinum treatment. The toxicity has been acceptable, and subsequent management has not been compromised.

Surveillance for stage I non-seminomatous germ cell tumours of the testis: the optimal protocol has not yet been defined.

Forty-six patients with clinical stage I testicular non-seminomatous germ cell tumours were followed up according to a protocol of active surveillance between 1979 and 1987. The median follow-up time was 40+ months. Thirteen patients (28%) relapsed, predominantly in retroperitoneum and/or lung. Ten of these relapses (76%) occurred within 8 months of orchiectomy. Relapses occurred in 7/35 T1 tumours and 5/10 T2 to T4 tumours. No correlation was detected between the histological type and relapse rate. Three late relapses were diagnosed at 23, 29 and 36 months. Eleven of the relapsed patients remain in prolonged complete remission after PVB chemotherapy +/- surgery; one patient, who initially refused treatment at the time of relapse, has died. Another relapsed with predominant elements of rhabdomyosarcoma intermingled with malignant teratoma in a bone metastasis. He had a partial response to PVB chemotherapy but subsequently died. Thirty-four patients (74%) did not undergo lymphography (LG) and had a higher relapse rate (11/34) than those who had LG (2/12); this was not a statistically significant difference in this small series. The policy of active surveillance is not yet the "state of the art" and should be under constant scrutiny with respect to safety and practice.

Oral cyclophosphamide for the management of hormone-refractory prostate cancer.

Thirty patients with hormone-refractory prostate cancer were treated with cycles of oral cyclophosphamide (100 mg/m2/day for 14 days, with a 14-day gap). Eighteen patients had a significant improvement in symptoms of advanced disease, 6 had objective partial remissions and 13 had stabilisation of disease (criteria of National Prostatic Cancer Project). The median survival from the time of diagnosis was 33.3 months, and from the commencement of cyclophosphamide 12.7 months. The treatment was well tolerated. oral cyclophosphamide is active in the treatment of advanced hormone-refractory prostate cancer and yields symptomatic and objective remissions without undue side effects. This observation requires validation, with further testing of its impact on survival in randomised clinical trials.