Clinical experience with mitomycin C in large infrequent doses

Abstract

One hundred and six patients (103 solid tumors, three lymphomas) were treated with large infrequent doses of mitomycin C. Thirteen patients in this group received combined radiation and chemotherapy and were evaluated separately. Most patients received 50 mg of the drug in a divided dose during the first week of treatment. After 6 weeks, maintenance injections of 10 to 30 mg of the drug were given to responsive patients at 4‐ to 6‐week intervals. Twenty‐two per cent of the patients showed a 50% reduction in tumor mass for a month or longer. Patients with breast and gastrointestinal carcinoma responded most frequently. The remission rates and durations are similar to those of published studies using other dosage schedules. Toxic effects have been similar though possibly less frequent. There appears to be no therapeutic advantage in using large infrequent doses of the drug; however, the time‐saving to both patient and medical staff has been significant.

The haemotoxicity of mitomycin in a repeat dose study in the female CD‐1 mouse

“…However, after a single MMC dose, the nadir for leucopenia was evident at 3½ weeks, and for thrombocytopenia the nadir was at 4 weeks post-dosing. Crooke & Bradner (1976) also reported that anaemia was commonly seen with all treatment regimens, but this was less severe than the effects on platelets and leucocytes; similar observations were described by Godfrey & Wilbur (1972) and Montes et al (1993).…”

“…In a review of MMC toxicity, Crooke & Bradner (1976) reported that the most frequently used schedule of MMC administration was 50 mg/kg/day for 6 days and then every other day until toxicity was manifested. Crooke & Bradner (1976) also reported that anaemia was commonly seen with all treatment regimens, but this was less severe than the effects on platelets and leucocytes; similar observations were described by Godfrey & Wilbur (1972) and Montes et al (1993). However, after a single MMC dose, the nadir for leucopenia was evident at 3½ weeks, and for thrombocytopenia the nadir was at 4 weeks post-dosing.…”

“…In man, MMC may cause delayed, cumulative bone marrow suppression with a sometimes profound leucopenia and thrombocytopenia (Godfrey & Wilbur 1972;Jones et al 1980;Zein et al 1986;Veeder et al 1992;Hortobagyi 1993;Medina et al 2001). In a review of MMC toxicity, Crooke & Bradner (1976) reported that the most frequently used schedule of MMC administration was 50 mg/kg/day for 6 days and then every other day until toxicity was manifested.…”

“…MMC acts as an alkylating agent after metabolic activation, mainly in the liver, and suppresses the synthesis of nucleic acids (Dollery 1999;Sweetman 2002). MMC is used in the palliative treatment of solid tumours particularly adenocarcinomas of the pancreas and stomach (Godfrey & Wilbur 1972) but also in the treatment of a large range of other tumours including those of the bladder, colon, rectum, lung, liver, prostate, cervix, breast, skin, oesophagus and eye (Karanes et al 1986;Reynolds 1989;Veeder et al 1992;Hortobagyi 1993;Sweetman 2002). MMC has a wide spectrum of activity and is generally used in combinations with other cytotoxic drugs (5-fluorouracil, adriamycin, CCNU, vindesine, bleomycin, cisplatin and isosfamide).…”

Mitomycin C in large infrequent doses in breast cancer

“…However, other early investigational work suggested that an intermittent dosage schedule might be less toxic as well as more efficacious in producing tumor response (15)(16)(17)(18)(19)(20). A prior study done at this institution investigated the administration of mitomycin C in large infrequent doses t o 106 patients with various types of tumor including breast (21). That study demonstrated that toxicity and therapeutic effect did not differ significantly from studies using small daily doses but that the time saved and the greater convenience to both patient and physician were considerable by using the large infrequent dosage schedule.…”