SummaryBackgroundIn metastatic renal cell carcinoma combinations of interferon alfa-2a, interleukin-2, and fluorouracil produce higher response rates and longer progression-free survival than do single agents. We aimed to compare overall survival in patients receiving combination treatment or interferon alfa-2a.MethodsRE04/30012 was an open-label randomised trial undertaken in 50 centres across eight countries. 1006 treatment-naive patients diagnosed with advanced metastatic renal cell carcinoma were randomly allocated (1 to 1) by minimisation to receive interferon alfa-2a alone or combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil. Treatment was not masked. The primary endpoint was overall survival. Treatment groups were compared with a non-stratified log-rank test. Analysis was by intention to treat. This study is registered, number ISRCTN 46518965.Findings502 patients were randomly assigned to receive interferon alfa-2a and 504 to receive combined treatment. Median follow-up was 37·2 months (24·8–52·3). Median overall survival was 18·8 months (17·0–23·2) for patients receiving interferon alfa-2a versus 18·6 months (16·5–20·6) for those receiving combination therapy. Overall survival did not differ between the two groups (hazard ratio 1·05 [95% CI 0·90–1·21], p=0·55; absolute difference 0·3% (−5·1 to 5·6) at 1 year and 2·7% (−8·2 to 2·9) at 3 years). Serious adverse events were reported in 113 (23%) patients receiving interferon alfa-2a and 131 (26%) of those receiving combined treatment.InterpretationAlthough combination therapy does not improve overall or progression-free survival compared with interferon alfa-2a alone, immunotherapy might still have a role because it can produce remissions that are of clinically relevant length in some patients. Identification of patients who will benefit from immunotherapy is crucial.FundingUK Medical Research Council.

Seven hundred and four patients with bladder cancer treated by radiotherapy at the London Hospital between 1965 and 1974 have been followed for a minimum period of 5 years. Invasive tumours were usually treated by radical radiotherapy. Cystectomy was reserved for patients whose tumours did not respond to radiation, recurred later on, or who developed complications from radiotherapy. The crude 5-year survival rate for T3 tumours in this series was 38%--similar to that obtained in other centres using pre-operative radiation followed by cystectomy, but this overall figure conceals the important difference between 2 distinct tumour populations. Nearly half of these tumours appear to be radiosensitive, giving a 56% crude 5-year survival rate for T3 tumours. The remainder are radioinsensitive, with only a 17% crude 5-year survival rate for T3 tumours. When there is a good initial response to radiotherapy there would seem to be no necessity to insist upon cystectomy.

This work found no association between treatment for testis cancer and the development of osteoporosis. Screening the whole population of testis cancer survivors for osteoporosis in the long term is not necessary; however, targeting specific patients with risk factors may be warranted.

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A retrospective analysis of the prognostic value of pretreatment histology and expression of human chorionic gonadotrophin (B-hCG) was carried out in 100 invasive (T2/T3) transitional cell carcinomas of the bladder treated in a uniform manner. After transurethral resection of the tumour, all patients received a course of radical radiotherapy, with salvage cystectomy for those who failed to respond. Forty-nine of 100 patients responded to radiation; thus 51 did not. Forty-seven of 60 (78%) patients whose tumours contained areas of squamous differentiation and 22 of 29 (76%) of tumours staining positively for HCG failed to respond to radiotherapy. Twenty-two of 23 (96%) patients with tumours that had both these features did not respond to radiotherapy. The other histological features studied (grade of tumour, necrosis, inflammation, vascular invasion, and growth pattern) appeared unrelated to each other or to clinical outcome.

It is more than 80 years since the first attempts were made to immunize human cancer patients against their own tumors (for review see reference 1). As yet, there are no immunological manipulations of proven value in terms of ensuring long-term cure, though there are randomized control studies demonstrating short-term prolongation of survival in patients with acute myelogenous leukemia receiving bacille Calmette-Guerin (BCG) 1 with or without aUogeneic leukemic blasts (for review see reference 2). In experimental animals, particularly inbred mice, it has been considerably easier to demonstrate tumor-specific antigens, both by serological and cell-mediated techniques and to prolong survival by immunizing against these antigens (3). Despite a welter of publications, there are few studies in human tumor systems where the concept of tumorspecific antigens has been clearly established and universally confirmed. In particular, though many authors have demonstrated lymphocyte-mediated cytotoxicity against tumor lines in both normal individuals and patients with tumors (4, 5), evidence for Tlymphocyte-mediated autologous tumor cytotoxicity has been very difficult to establish.In vitro assays of transplantation rejection using the mixed lymphocyte culture and cell-mediated lympholysis tests, have provided clear insight into the nature of antigenic determinants necessary for generation of cytotoxic T cells. The pioneering studies of Eijsvoogel et al. (6) on HLA recombinant families demonstrated the need for two types of antigens, the first type coded for by genes closely associated with those of the HLA D locus cause lymphocyte activation, whereas the second class of determinants, closely associated with the serologically defined HLA A, B, and C locus antigens, acts as the target for the cytotoxic T lymphocytes. Eijsvoogel et al. (7) also showed that production of cytotoxic T lymphocytes was possible even if the lymphocyte-activating determinant and serologically defined antigens were present on different cells. Zarling et al. (8) applied this principal to study leukemia patients and then reported one patient where stimulation of remission lymphocytes by mitomycin C inactivated autologous myeloblasts and a third party inactivated allogeneic lymphocytes in short-term culture led to the production of cytotoxic cells against autologous blasts but not the remission lymphocytes.We report and confirm this observation in a series of 14 patients with acute myelogenous leukemia and investigate the nature of the effector cell, the helper * Present address:

Objective To investigate the ef®cacy of low-dose stilboestrol (SB) with hydrocortisone in patients with advanced prostate cancer refractory to androgen suppression. Patients and methods Thirty-four consecutive patients (median age 70 years, range 51±83) with metastatic disease who progressed on hormone therapy, as shown by recurrent/worsening symptoms and an increase in prostate-speci®c antigen (PSA) level, were recruited and discontinued hormonal treatment before starting SB. Patients received SB (1 mg/day) combined with hydrocortisone (40 mg/day). In an attempt to reduce the incidence of thrombo-embolic events, aspirin (75 mg/day) was also added. Results Stilboestrol was the second-line treatment in 19 patients and the third or fourth in 15. The median (range) duration of treatment with SB was 5 (0.5±21) months and the median follow-up 7.5 months, with 18 patients still alive and 14 still on treatment. Of 29 symptomatic patients, 24 had symptomatic improvement and ®ve had no clear bene®t; the median duration of bene®t was 6 (2±21) months. The PSA level decreased by 0±50% in six patients, by 50±90% in 13 and by >90% in eight, while there was symptomatic improvement in these three categories in ®ve, 11 and seven patients, respectively. The median times to PSA nadir and progression were 4 and 6 months, respectively. Some thrombo-embolic events and¯uid retention occurred but overall the treatment was well tolerated. Conclusion Low-dose SB with hydrocortisone is effective in refractory prostate cancer, although there is some toxicity. Randomized studies against hydrocortisone or SB alone are needed to establish the cost/bene®t ratio of this combination.

One hundred and eighty-two patients with invasive (T2/T3) bladder cancer were treated by radical radiotherapy at the London Hospital between 1974 and December 1985. Cystectomy was reserved for patients whose tumours either did not respond completely to radiation or recurred later, provided they were fit for surgery and had not developed distant metastases. The overall corrected 5-year survival rate was 40%; 75 patients responded to radiation and did not relapse during the period of follow-up; 20 patients had an initial response to radiation but subsequently relapsed, with a 5-year survival rate following relapse of 20%. Of these, 11 patients had a cystectomy with a 5-year survival following relapse of 36%, whereas all 9 patients who did not have a cystectomy died within 3 years; 87 patients who did not respond to radiation had a 5-year survival rate of 18%. Of these, 22 patients underwent salvage cystectomy with a 5-year survival of 47%, whereas the 65 patients who did not have a cystectomy had a 5-year survival of 3%. These results justify a policy of radical radiotherapy and salvage cystectomy rather than elective cystectomy in the treatment of invasive bladder cancer.