Irradiation therapy with multiple small fractions per day in urinary bladder cancer.

In a clinical trial 168 patients with carcinoma of the bladder, T2-T4, were randomized to one of two treatments; 1 Gy 3 times a day to a total of 84 Gy or 2 Gy once a day to a total of 64 Gy. Local eradication of the tumour in the bladder cystoscopically and cytologically at 6 months after completion of treatment and patient survival were analyzed. The results favoured significantly the patients treated with 84 Gy. All patients were followed 5-9 years. The survival was significantly improved in patients with T3 lesions treated with 84 Gy (p less than 0.01). Complications in the bowel requiring surgical treatment were not significantly different between the two groups of patients. The results indicate a therapeutic gain by hyperfractionated radiotherapy in comparison to conventional fractionated radiotherapy.

Interferon therapy in disseminated renal cell carcinoma.

Twenty patients with pulmonary metastases of renal cell carcinomas have been treated in a randomized study with either leucocyte interferon in daily doses of 3 x 10(6) I.U.i.m or irradiation of both lungs in a calculated mean central dose of 10 Gy in 4 weeks in combination with bleomycin and vincristine. Most patients had a short time to progression of their disease. Three patients in the interferon group had complete response (CR) and partial response (PR) and one patient in the other group had PR. The numbers of patients in both arms of the study are too small to allow any conclusions whether beneficial effects are more frequent in one group than in the other, but there is a more favourable tendency in the interferon group.

Irradiation, chemotherapy and surgery in esophageal cancer: a randomized clinical study. The first Scandinavian trial in esophageal cancer.

In a randomized trial, irradiation alone (35 Gy) or irradiation (30 Gy) and bleomycin was given as preoperative treatment of esophageal cancer. In inoperable patients, a split course of irradiation alone (63 Gy) or irradiation (55 Gy) and bleomycin was given. Bleomycin doses were 5 mg i.m. 1/2-1 h before each irradiation dose. No benefit was obtained by addition of bleomycin to irradiation concerning survival or palliation of dysphagia. No benefit of bleomycin was seen either in any subgroup of patients according to different primary tumour classifications, histopathological gradings or localizations of tumour. In patients with advanced/metastatic disease, bleomycin and adriamycin treatment gave a significantly longer survival than bleomycin alone. It was shown that the presence of T1 tumours was a significant prognostic factor for long-term survival and that performing a radical operation was a significant advantage for a longer survival. Female patients treated with irradiation with or without bleomycin survived significantly longer than males, but in operable patients there was no significant difference between the two sexes with regard to survival.

Chemotherapy in advanced urinary bladder cancer.

In our investigation of different chemotherapy protocols, the best results in recent years were obtained with a combination of cisplatinum and doxorubicin in patients with recurrent urinary bladder cancer. This applied both to the local bladder tumor and the metastases. With respect to the cases of advanced localized bladder cancer, refined surgery or more developed equipment in radiotherapy, even developing new particles or rays, presumably will give only marginal effects on eradication of the tumor. A new approach may be to give a combined therapy of CDDP and doxorubicin before surgery and/or radiotherapy; a pilot study is going on in Stockholm. Experience so far has shown that CDDP together with radiotherapy or after preoperative irradiation followed by cystectomy is not tolerable to the patients. Between 40 and 50 per cent of them failed to fulfill the treatment.

Intravesical chemotherapy in urinary bladder cancer.

Monthly instillation therapy with Adriamycin in a standardized dose of 300 ng/ml/h together with a phosphate buffer at pH 7.4 seems to give satisfactory results in patients with primary bladder carcinoma in situ and in patients with secondary carcinoma in situ of the bladder who have previously received full courses of irradiation. The side-effects are transient and few.

Bestatin treatment and the peripheral lymphocyte population in cancer patients.

Bestatin, a substance produced by Streptomyces olivoreticuli, inhibits certain cell-membrane-associated enzymes and has been shown to augment immune responses in experimental animals. We have determined whether bestatin medication changed the peripheral lymphocyte population in 15 advanced cancer patients. After 2 weeks of daily, 30 mg oral bestatin medication, the lymphocyte counts remained essentially unchanged, but the frequency of E-rosette-forming lymphocytes increased. In vitro stimulation of the lymphocytes with PHA or PPD remained essentially unchanged while the natural-killer activity of the lymphocyte population increased in most patients. Bestatin treatment caused no detectable side effects.

Estramustine phosphate therapy in carcinoma of the prostate.

Estramustine phosphate, a nor nitrogen mustard derivative of estradiol 17-beta-phosphate, was introduced in the treatment of prostatic carcinoma in 1966. Until March 1975, 466 patients have been reported on this treatment in open clinical trials: 82% of the patients were in stage IV. In 402 patients, nonresponsive to previous estrogen therapy, signigicant improvement occurred in 55%. In 64 previously untreated patients there was a favourable response in 83%. Side-effects were mainly bone marrow suppression. liver disturbance, thrombophlebitis following intravenous injection, and gastrointestinal troubles, mainly following oral administration. A prospective, randomized study comparing oral estramustine phosphate and conventional estrogen therapy in carcinoma of the prostate is in progress.

Bestatin treatment enhances the recovery of radiation induced impairments of the immunological reactivity of the blood lymphocyte population in bladder cancer patients.

Bestatin, an immunostimulating substance of microbial origin, was examined for its capacity to augment immune responses of blood lymphocytes in bladder cancer patients having received a full course of local irradiation (64 Gy). Following irradiation the patients became lymphopenic and the lymphocytes exhibited impaired mitogenic responses to phytohemagglutinin (PHA) and purified protein derivative of tuberculin (PPD) and reduced poke weed mitogen induced secretion of immunoglobulins in vitro. Patients who were randomized to receive daily oral Bestatin treatment exhibited enhanced recoveries of PHA- and PPD-responses and enhanced recovery of the IgM secreting capacity compared to irradiated patients who did not receive Bestatin. Repopulation of the blood lymphocyte population, however, was not enhanced by Bestatin treatment. It is concluded that Bestatin treatment may enhance the recovery of radiation induced functional defects of the immune system in cancer patients.

Immunological and haematological monitoring in bladder cancer patients receiving adjuvant bestatin treatment following radiation therapy. A prospective randomized trial.

In a prospective randomized trial the clinical value of Bestatin, a low molecular weight immunomodulator, is being examined in patients having completed a full course of local radiation therapy for bladder cancer. At termination of irradiation (64 Gy in eight weeks) the patients are divided into two treatment arms: (i) 10 mg of Bestatin orally three times daily without breaks for at least one year and (ii) no further adjuvant treatment. Routine haematological monitoring of 68 patients for a period of up to two years did not reveal any differences between the two groups. Studies on the blood lymphocyte population, however, showed a significantly elevated frequency of cells forming rosettes with sheep erythrocytes after one month of Bestatin treatment. Upon continuation of treatment, however, this value declined and reached the level of the control patients at three months. The frequencies of lymphocytes with Fc-receptors for IgG or complement were unaffected by Bestatin. Spontaneous cytotoxicity against Chang cells appeared to be increased during the first three months of Bestatin treatment in those patients who survived for more than 18 months. No increase was observed in patients who died earlier. Although the above data seem to indicate that Bestatin should be administered at higher doses and intermittently instead of continuously, our preliminary results on disease-free survival in a limited patient material seem to be in favour of the Bestatin treated patients.

A low dose-fractionation shceme for the radiotherapy of carcinoma of the bladder. Experimental background and preliminary results.

Experimental observations are described which form the basis of a low dose-fractionation scheme designed in an attempt to circumvent the problem presented for radiotherapy by the particular radioresistance of poorly oxygenated cells. In a preliminary investigation the scheme was tested in the treatment of carcinoma of the bladder. A total of 45 patients were included in the trial, randomized to be treated according to either of two fractionation schemes. Scheme I : 100 rad 3 times a day, 5 days a week, a total tumor dose of 8 400 rad, 2 weeks of rest in middle of the treatment period. Scheme II : 200 rad once a day, 5 days a week, a total tumor dose of 6 400 rad, 2 weeks of rest in the middle of the treatment period. The results suggest an improved therapeutic ratio with Scheme I in comparison to Scheme II.

[Adriamycin instillations in carcinoma in situ of the bladder]. / Adriamycin-Instillationen bei Carcinoma in situ der Harnblase.

Several authors have described the regressive effect of the instillation of adriamycin on the cell appearance of carcinoma in situ. This applies to both weekly and monthly administration. The problem lies in the interpretation of the cytologic picture after instillation. DNA analysis could possibly improve the diagnostic reliability.

Estramustine phosphate therapy in poorly differentiated carcinoma of the prostate.

Ninety patients with poorly differentiated prostatic carcinoma have been treated with Estramustine phosphate (Estracyt). Seventeen of them had clinically metastases and had had no previous therapy. Seventy-three were initially given oestrogens and/or irradiation. Objective response was observed in 59%. The best effect was seen in patients primarily untreated.

External irradiation therapy in carcinoma of the prostate.

107 patients with poorly differentiated prostatic carcinoma without metastases received local irradiation at the Karolinska Hospital from 1965 through 1973. The majority of the patients had received previous hormone therapy and had a progressive local disease. Many of them were given estrogens even after radiotherapy. All the patients were followed for at least 5 years. Complete regression of the palpable prostatic carcinoma mass was registered in about 70% of the cases. A 33% 5-year survival was obtained. This is significantly higher than the survival of the comparable group of patients receiving only hormones.

Cyclophosphamide-prednisolone therapy in advanced prostatic carcinoma.

Cyclophosphamide and prednisolone therapy was given to 83 patients with hormone-resistant disseminated carcinoma of the prostate. In 7 cases there were objective signs of regression of metastases. Significant reduction of elevated acid phosphatase activity was recorded in 11 cases, in 2 of them to normal range. 55 patients experienced pain relief, 26 of them very good. In the majority of cases duration of the remission was shorter than 6 months, in 2 cases it lasted more than a year.

Estramustine versus conventional estrogenic hormones in the initial treatment of highly or moderately differentiated prostatic carcinoma. A randomized study.

In a prospective randomized multicenter trial patients with highly or moderately differentiated prostatic carcinoma, previously untreated, were allotted either to oral Estramustine phosphate or to intramuscular polyestradiol phosphate plus oral ethinyl estradiol. As regards frequency and duration of tumour remission there was no statistical difference between the two groups. Nor did they differ significantly with respect to adverse reactions. This is an interim report and will be followed later on by a final evaluation.