A randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced transitional cell carcinoma: results and a report on prognostic factors in a Medical Research Council study

Abstract

of CMV. This translates to an absolute improvement in 1-year survival of 13%, 16% in MV and 29% in CMV. The median survival for CMV and MV was 7 months and 4.5 months respectively. Two hundred and eight patients objectively progressed or died. The hazard ratio was 0.55 (95% Cl 0.41-0.73, P-value = 0.0001) in favour of CMV. Two hundred and nine patients symptomatically progressed or died. The hazard ratio was 0.48 (950°o Cl 0.36-0.64. P-value = 0.0001) in favour of CMV. The most important pretreatment factors influencing overall survival were WHO performance status and extent of disease. These two factors were used to derive a prognostic index which could be used to categorize patients into three prognostic groups. We conclude that the addition of cisplatin to methotrexate and vinblastine should be considered in patients with transitional cell carcinoma, taking into account the increased toxicity.Keywords: chemotherapy; transitional cell carcinoma: randomized Transitional cell carcinomas (TCCs) mav arise at anx site within the unrnarx tract and are a source of considerable morbiditx and mortalitv. In 1994. there A-ere 5300 deaths from this disease in the UK (Cancer Research Campaign. 1995). Approximately 90% of these cancers arise in the bladder. occumrng at a median ag,e of 65 Xears. Treatment of patient.s with disease confined to the bladder (1T2 or T3) w-ith radiotherapy or cystectomy results in cure in 30-40%7 of cases. Patients w-ith metastatic disease hax-e a much poorer prognosis. with less than 5%-alix-e at 5 vears (Saxman et al. 1997).During the last 15-20 years. chemotherapy. predominantly using the drugs methotrexate. Xinblastine. cisplatin and doxorubicin. has been w-idelx used to treat these cancers (Sternberg. 1995). Early randomized trials using combinations of these drugs. (Sternberg et al 1985(Sternberg et al . 1988(Sternberg et al . 1989). a drug combination incorporating all these drugs. and CMV (omittinc doxorubicin: Hark-er et al. 1985: Jeffern et al. 1992). large improvements in remission rate were reported in single-institution studies. with reports of longterm sunrival in 20'c of patients in one study (Sternberg et al. 1989). In a subsequent randomized trial. howex er. comparing single-agent cisplatin wxith M-VAC (Loehrer et al. 1992). the essentially palliative nature of these treatments w as demonstrated.W'hile M-VAC proxed capable of increasing median sun-ix al time from 8 months to 12 months. a 5-y ear progression-free surnival of only 4%/c wxas reported (Saxman et al. 1997 resulting in marked morbidity-for the majority of patients and treatment-related mortality in up to 4%,c of cases (Loehrer et al. 1992). Cisplatin itself is probably responsible for most of the impairment of quality of life. and the precise role of this drug in the management of these cancers has not been clearlv demonstrated. Cisplatin-based treatment can also be inconvenient to the patient. usually requirinc hospitalization for administration. In the trial comparing single-agent cisplatin with M-VAC (Loehre...

Prognostic impact of FAS/CD95/APO-1 in urothelial cancers: decreased expression of Fas is associated with disease progression

“…However, as grade 2 UC are still heterogeneous, there is a necessity to find new markers to subclassify grade 2 tumours. In the treatment of advanced stage bladder cancers, combination chemotherapy including platinum has revealed promising results (Mead et al, 1998). However, multidrug-resistant bladder cancer shows a poor prognosis.…”

Predictive factors for response and prognostic factors for long-term survival in consecutive, single institution patients with locally advanced and/or metastatic transitional cell carcinoma following cisplatin-based chemotherapy

“…They concluded that although with cisplatin based multidrug chemotherapy response rates were high, the lack of randomised comparisons with best supportive care precludes definite conclusions regarding survival benefit gained. The differences observed in median survival between less intensive regimes (4.5 months with metotrexate/vinblastine [22]) and recent, more intensive chemotherapy (up to 13Á15 months with cisplatin based regimes [2]) however strongly suggests a survival benefit in selected patient groups. The basis on which to select patients for chemotherapy is however undocumented.…”

Current management of muscle-invasive bladder cancer

“…Unfi t patients represent 30% of patients with advanced disease [68]. Survival in "fi t" patients is over a year, with a complete response rate ranging from 15% to 30% [65,66]. Which CT is recommended for "fi t" patients?…”

“…Cisplatin-based combination CT is the standard care in the management of metastatic urothelial cancer [65,66]. The EORTC has categorised patients as either "fi t" for cisplatin or "unfi t" if they have poor renal function (creatinine clearance <60 ml/min), ECOG 2, grade 2 hearing loss, grade 2 neuropathy and/or New York Heart Association Class III heart failure [67].…”