A randomized comparison of tamoxifen with surgical oophorectomy in premenopausal patients with advanced breast cancer.

We randomized 122 premenopausal women to receive tamoxifen or to undergo a surgical oophorectomy. Of 54 evaluable women treated with tamoxifen, 24% had an objective response, as compared with 21% of 53 women having an oophorectomy. The median duration of response for tamoxifen (20 months) was longer than that for surgical oophorectomy (7 months), but this did not achieve statistical significance (P = .056). Overall median survival was 15 months for 58 patients receiving tamoxifen and 25 months for 53 patients undergoing oophorectomy (P = .18). Toxicity was greater in those undergoing oophorectomy, though both treatments were well tolerated. In those premenopausal women for whom hormonal therapy is indicated, tamoxifen is a suitable alternative to surgical oophorectomy.

A pilot study of accelerated fractionation in the radiotherapy of invasive carcinoma of the bladder.

24 patients with muscle invasive carcinoma of the bladder were treated in a pilot study of twice daily fractionation at radiation doses of 1.8-2.0 Gy per fraction to total doses of 54-64 Gy to the bladder and 39.6-44 Gy to the whole pelvis. The treatment aim was to give 32 fractions in 22 days. The interfraction interval was a minimum of 6 h. The principle objective was to record acute and late tolerance, but local control and survival data is also presented. Acute radiation morbidity was scored according to the RTOG system. Grade 2 large bowel effects were seen in 52% of patients, Grade 3 effects in 26% and there was one Grade 4 and one Grade 5 effect. The mean duration of effect was 4.5 weeks although the more severe reactions were also more protracted. Grade 2 urinary effects occurred in 30% and Grade 3 in 17% of patients. The mean duration of effect was 7.2 weeks. There were no Grade 4 or 5 acute urinary effects. Late radiation morbidity was scored according to the EORTC/RTOG system and was assessable in 16 cases who survived more than 6 months. There were two cases (12%) of Grade 1 bowel toxicity, two cases of Grade 1 and three of Grade 2 urinary toxicity. There were no cases of late skin effects. Actuarial analysis at 2 years shows a local control probability of 56% and survival probability of 35%.

Treatment of carcinoma of the breast with high dose oral medroxyprogesterone acetate: does increased bioavailability improve the therapeutic ratio?

Medroxyprogesterone acetate (MPA) is regarded as a valuable hormonal therapy for metastatic breast cancer. The drug is manufactured by more than one pharmaceutical company, and one particular brand of oral MPA (Provera Tablets, Upjohn) has been reformulated to incorporate micronized particles, providing significantly enhanced bioavailability. The response rate and side-effect data from a pilot study, which used the old formulation Provera Tablets 100 mg at a dosage of 800 mg/day in 28 patients with recurrent breast cancer after treatment with tamoxifen, are compared with those from another study in which 59 similar patients received 800 mg/day of new formulation Provera Tablets 200 mg. Neither of these studies, conducted in the United Kingdom, has previously been published. The response rates were similar in both studies, but there were higher incidences of significant weight gain and increased blood pressure in those patients treated with the new formulation. These side effects have been noticed by other workers employing new formulation MPA at a dosage of 800 mg per day, while it has been reported that reducing the dosage to 400 mg perday is accompanied by a lower incidence of side effects, without affecting the response rate. It is concluded that the increased serum levels of MPA, made possible by the micronized product, do not favourably influence the response of metastatic breast cancer to therapy, but may be associated with a higher incidence of side effects. Reducing the dosage of the new formulation MPA to 400 mg/day may allow a more acceptable side-effect profile, without loss of therapeutic efficacy. Such a dose reduction would make this brand of MPA more cost effective.

Treatment of multiple superficial papillary tumors of the bladder by intracavitary yttrium-90.

Intravesical Y-90 was used in 38 patients with multiple papillary T1 tumors considered beyond control by cystodiathermy. Of the 32 patients available for 3-year observation 19 (60 per cent) were alive after 3 years, 6 had died of progression of the tumor and 7 had died of other causes. Prolonged imporvement was noted in 23 patients (72 per cent). The complication rate was moderate and only 2 patients required cystectomy for symptoms caused by radiation damage alone.

A trial of bleomycin versus adriamycin in advanced carcinoma of the bladder.

Thirty-seven patients were studied in a controlled clinical trial to assess the value of Adriamycin and Bleomycin in the treatment of advanced carcinoma of the bladder. The previously reported high response rates for both drugs were not observed in this trial. Administration of Bleomycin was accompanied by a toxicity rate so high that treatment had to be abandoned. Neither Adriamycin nor Bleomycin, therefore, used as single agents, have a role in the chemotherapy of advanced bladder cancer. Other agents should be investigated and assessed by controlled clinical trials that are disease-orientated rather than drug-orientated.

The effect of immediately preoperative adjuvant radiotherapy in the surgical treatment of primary cutaneous malignant melanoma.

A historical series of patients with primary cutaneous malignant melanoma is reviewed. These patients had been treated with a single therapeutic dose of irradiation to the tumour and surrounding skin immediately before surgical excision. Some patients had also received a single necrotising dose of radiotherapy to the tumour itself. Recurrence and survival rates have been examined retrospectively in the light of reviewed histology, and compared with other published series. Preoperative radiotherapy was found to have no significant influence on the outcome of surgical treatment of primary malignant melanoma.

Treatment of multiple superficial transitional cell carcinoma of the bladder with intravesical yttrium-90.

Thirty-eight patients with extensive multiple superficial transitional cell carcinoma of the bladder which could not be controlled endoscopically were treated with intravesical yttrium-90. Nineteen are alive at between 1 and 9 years. Short-term control of the disease was achieved in most patients. In those followed up for at least 3 years, 48% remained alive and well and 36% avoided cystectomy or other major treatment.

A randomized controlled trial of prophylactic cytotoxic chemotherapy in potentially curable breast cancer.

A randomized controlled trial of the value of oral adjuvant cytotoxic chemotherapy in the treatment of potentially curable breast cancer has been in progress in the Oxford Region since 1977. Eighty-seven patients were allocated to treatment with melphalan 0.2 mg/kg for 5 consecutive days every 6 weeks for 2 years; 98 patients were allocated to treatment with oral combination therapy consisting of melphalan 10 mg daily for 5 consecutive days, plus methotrexate 15 mg and 5-fluorouracil 250 mg on the first day, courses being repeated every 6 weeks for 2 years; and 88 patients were allocated to a control group which received no adjuvant chemotherapy. So far, 125 patients have suffered a recurrence of breast cancer and 85 have died. No statistically significant differences in outcome are apparent between the three treatment groups, although there is some indication of a beneficial effect of chemotherapy on disease-free interval in pre-menopausal women. Toxic effects of treatment, notably nausea, vomiting and bone marrow depression, have been moderately severe. In our view, the beneficial effects of current adjuvant cytotoxic chemotherapy, if any, are too modest to justify the suffering which such treatment can cause at a time when a woman with breast cancer might otherwise expect to feel physically well.

Problems associated with iridium-192 wire implants.

Three incidents are reported, from different radiotherapy centres, in which an implanted iridium-192 wire remained in the tissues of a patient after withdrawal of the plastic tubing in which it was contained. In each case the instrument used to cut the wire had probably formed a hook on the end of the wire which caused it to catch in the tissues. Detailed recommendations are made for avoiding such incidents in the future, the most important of which is that the patient should be effectively monitored after the supposed removal of all radioactive sources.