Bladder Cancer: Inter‐relationships between Chemotherapy and Radiotherapy

Abstract

There has been increasing interest in the role of chemotherapy as primary treatments for patients with urothelial cancer and because of the poor prognosis of locally advanced tumours with conventional treatment, trials have been initiated comparing radiotherapy with chemotherapy as primary therapies. In this context it is important to assess the relationship between the responses to chemotherapy and radiotherapy, and this we have examined in 64 patients treated with MVMJ (methotrexate, vinblastine, mitozantrone and carboplatin). Either a complete or a partial response was found in 29 of the 64 patients, 15 had stable disease and 13 had progression of disease. Seven patients died within the first treatment month. The survival of the responding patients ranged from 114 to 1184 days. Six of 15 patients who had had pelvic irradiation prior to chemotherapy responded to MVMJ, the maximum duration of response being more than 3 years. Twenty-two patients had radiotherapy following their chemotherapy. One of 13 patients not responding to MVMJ had a transient response to radical radiotherapy. Only 1 of 9 patients responding to chemotherapy and then relapsing responded to subsequent radical radiotherapy. Patients with metastatic disease or with recurrent disease after radiotherapy have a worthwhile chance of responding to chemotherapy and achieve durable remissions. In contrast, radiotherapy appears relatively ineffective in patients whose disease progresses or relapses after chemotherapy given as primary treatment with curative intent.

Chemotherapy for urothelial tract malignancies: Breaking the deadlock

“…One group has evaluated a four-drug program in which mitoxantrone was used to replace adriamycin and carboplatin was used instead of cisplatin. Complete responses were observed in 5 (23%) patients with metastatic disease and partial responses in I 1, for an overall response proportion of 52% (95% confidence limits 27-68Oh) [38,39]. These results are somewhat surprising in light of the low response proportions observed with mitoxantrone as a single agent [40].…”

“…Combinations of cisplatin and carboplatin have also been investigated [175,176]. In addition, cells that are resistant to cisplatin have been shown in the laboratory and the clinic to be crossresistant to radiation therapy [165,177,178], which is of potential importance in clinical trials using chemotherapy and radiation therapy in a sequential fashion. In one cell line, cross-resistance between cisplatin and methotrexate was observed.…”

Bladder cancer staging

“…Check cystoscopy may allow progression to be detected, but in general those patients considered at risk of developing invasive disease should be intensively staged, as this group may benefit from radical treatment alternatives, including radical radiotherapy and cystectomy. There is no general consensus about the optimal management of patients once invasive bladder cancer has developed, because clear survival benefits with different therapeutic approaches are difficult to detect [17–19]. Nevertheless, local control of disease is important for the patient’s quality of life, and local staging of disease is therefore important even if distant metastases are suspected.…”

An Overview of Mitozantrone

“…Incorporation of mitozantrone into combination chemotherapy regimes has been associated with an overall response rate in locally advanced tumours of 55% 38 . Comparison with standard CMV or MVAC chemotherapy would be justified.…”