Experience in the radical radiotherapy of cancer in the bilharzial bladder: the use of misonidazole.

The results of application of a protracted split-course radiotherapy regimen in T3 carcinoma in the bilharzial bladder are presented. A total dose of 70 Gy spread over 61 days was divided into four courses separated by gaps of 1, 2 and 1 week, respectively. Each of the first three sessions comprised eight fractions, 2.5 Gy each, while four such fractions were given during the fourth course. Patients were randomized between radiotherapy alone (32 patients) and radiotherapy plus misonidazole (MIS) (30 patients). The drug was given in a daily oral dose of 0.5 g/m2, 3.5 h prior to each radiation treatment. The treatment was well tolerated and MIS did not augment the radiation reaction. Mild or moderate peripheral neuropathy was experienced by 63% of patients of the group. Age and degree of upper obstructive uropathy were the most important determinants of the risk of neuropathy. The 2-year disease-free actuarial survival rates amounted to 58% and 44% in the MIS and radiotherapy alone groups respectively; the difference is not significant. The results were significantly better in case of transitional cell (67%) than squamous cell cancer (29%) but were independent of the histological grade. A strong correlation was found between the magnitude of tumour volume reduction after 40 Gy and the long-term end results.

The use of misonidazole in association with a three-fractions per day regimen in advanced head and neck epidermoid cancer. A pilot study.

Twenty-one patients with Stage III or IV head and neck epidermoid cancer were treated by a three-fractions per day radiotherapy regime plus misonidazole (MIS). An initial course of 45 Gy was used, spread over 12 days and divided into 30 fractions 1.5 Gy each with a 3-hour interval between fractions. A daily MIS dose of 1 g/m2 was given 2 hours prior to the first fraction. A boost dose of 22.5 Gy/5 days was given to 10 patients, 4 weeks after the initial course, using the same fractionation scheme. The local acute and chronic reactions were acceptable. Eight patients suffered mild reversible peripheral neuropathy. The mean MIS blood level corresponded to an enhancement ratio of about 1.45. The 1-year disease-free survival rate was 9/21 and was significantly greater in patients receiving the boost irradiation. The control rate of nodal disease was encouraging. Based on this pilot study, a prospective trial is proposed aiming at testing the usefulness of MIS in MDF regimens in advanced head and neck cancer, either as the sole method of treatment or as a preoperative measure.