Combination chemotherapy with methotrexate, vinblastine, adriamycin and cisplatin (M-VAC regimen) was administered to 12 patients with advanced epithelial cancer of the urinary tract in a clinical trial undertaken to assess clinical efficacy of this multiagent therapy. This series comprised 11 males and 1 female ranging in age from 46 to 76 years (mean age: 63), with performance status (PS) being rated 0 in 2, 1 in 5, 2 in 2, 3 in 2 and 4 in 1 of these 12 patients. The site of primary lesion was bladder in 8, renal pelvis in 3 and ureter in 1. Histologically, these tumors were all identified as transitional cell carcinoma (grade 3) with the exception of 1 mixed type (transitional cell carcinoma plus squamous carcinoma). Nine of the patients had already their primary tumor resected surgically while the remaining 3 had undergone only biopsy. The site of metastasis was lung in 7, bone in 4 and lymph nodes in 3. In consideration of the patients' general condition, the dosages of the chemotherapeutic agents were set at 80% of those recommended by Sternberg. Of the 9 patients with primary tumor resected, 1 died of chemotherapy; of the remaining 9 patients, the M-VAC regimen brought about CR in 1 and PR in 4, hence with a response rate of 62.5%. The 4 patients showing PR underwent surgical resection of residual tumor and 2 of them achieved CR and have been free of a recurrence during a 33- or 29-month period of the chemotherapeutic regimen.
Of the 3 patients who had undergone biopsy only and whose primary tumor remained unresected, 1 had a PR with the multiagent regimen, hence the response rate for this small subgroup was 33%. Aside from the bladder and recutus abdominis muscle which were involved in a very limited number of cases, lungs and lynph nodes were most responsive to the chemotherapeutic regimen of all organs involved, with respective response rates of 57% and 33%. Use of the M-VAC regimen was attended by leukocytopenia in 11 patients (91%) and by nausea, vomiting, anorexia and falling off of hairs in all patients. Impairment of renal function was mild, however. In conclusion, the M-VAC regimen proved to be effective against advanced epithelial carcinoma of the urinary tract, especially in cases of postoperative recurrence, but ample care must be taken to avoid or minimize unwanted side effects of this combination chemotherapy.