Preliminary Results of M-VAC (Methotrexate, Vinblastine, Doxorubicin and Cisplatin) for Transitional Cell Carcinoma of the Urothelium

Abstract

The M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) regimen was used to treat 25 patients with transitional cell carcinoma of the urothelial tract. Treatment consisted of monthly cycles of 30 mg. per m.2 methotrexate, followed 24 hours later by 3 mg. per m.2 vinblastine, 30 mg. per m.2 doxorubicin and 70 mg. per m.2 cisplatin, and concluded with repeat vinblastine and methotrexate on days 15 and 22. Significant tumor regression was noted in 71 per cent of the patients. Complete clinical remission was observed in 12 of 24 patients (50 per cent, 95 per cent confidence limits 30 to 70 per cent) with bidimensionally measurable indicator lesions, 6 of whom had pathological confirmation. After surgical exploration 4 patients required downstaging to a partial remission. The median duration of response has not yet been reached at 9.5 plus months, range 4.5 plus to 16 plus. Five patients (21 per cent) had a partial clinical remission for 4 to 8 plus months, 1 had a minor response for 4 months and 1 had stable disease for 11 months. All metastatic sites responded, including bone (6 of 8 cases), liver (3 of 5), locoregional (12 of 17) and intravesical (6 of 7) disease. Toxicity included moderately severe myelosuppression that resulted in nadir sepsis in 4 patients and a drug-related death in 1, mild to moderate anorexia, vomiting, alopecia and renal dysfunction. These preliminary results suggest that treatment with methotrexate, vinblastine, doxorubicin and cisplatin is extremely effective against locoregional and disseminated urothelial tract tumors, with the expectation (95 per cent confidence limits) of inducing objective tumor regression in 53 to 89 per cent of the cases.

A phase I/II study of gemcitabine and fractionated cisplatin in an outpatient setting using a 21-day schedule in patients with advanced and metastatic bladder cancer

“…In 1985, the Memorial Sloan-Kettering cancer centre (MSKCC) investigated the four-drug regimen using MVAC (methotrexate, vincristine, doxorubicin, cisplatin) (Sternberg et al, 1985) in patients with TCC. They reported an overall response rate of 71%.…”

“…Indeed, a significant proportion of otherwise fit patients (around 50% in our institution) have a calculated glomerular filtration rate o60 mls min À1 , the usual cutoff for combination studies with cisplatin. Treatment with MVAC can result in clinically significant myelosuppression (up to 25% incidence of neutropenic fever and a 3% drug-related mortality) and significant mucositis (up to 50% incidence of grade 2 -3 mucositis) (Sternberg et al, 1985(Sternberg et al, , 1989Connor et al, 1989;Tannock et al, 1989;Igawa et al, 1990;Logothetis et al, 1990;Boutan-Laroze et al, 1991;Loehrer et al, 1992). Recent efforts to improve the outcome for patients with metastatic transitional cell carcinoma have focused on the identification of new drugs with single-agent activity and on their incorporation into platinum-based combination regimens.…”

Surveillance of urothelial carcinoma

“…There have also been few improvements in overall survival with therapies for metastatic TCC. The combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) had been the standard chemotherapy regimen since its development in the 1980s [31][32][33] until von der Maase et al demonstrated that the combination of gemcitabine and cisplatin (GC) had a better toxicity and tolerability profile. 34 Median survival, however, was not significantly different between the 2 regimens: 13.8 months with GC versus 14.8 months with MVAC.…”

Hypermethylation of tumor-suppressor gene CpG islands in small-cell carcinoma of the urinary bladder

“…7,[10][11][12] Platinum-based chemotherapy has been the mainstay of treatment for more than 20 years. 41 TCC is often sensitive to this chemotherapy regimen, theoretically in part because its promoter is not hypermethylated and MLH1 expression is maintained. In support of this hypothesis, the lone patient with detectable MLH1 methylation survived only 3 months after being diagnosed with T2N1M1 SCBC.…”