E4897 – Trial Results Summary for Patients

Title

Comparing the Effectiveness of Different Drug Combinations for Advanced Cancer of the Urothelium Which Cannot Be Controlled With Surgery (A Phase III Trial)

Sponsor

Eastern Cooperative Oncology Group through the NCI-sponsored Cancer Cooperative Group Program

Purpose of the Study

To slow, stop or decrease the growth of cancer of the urothelium and to compare and evaluate the effectiveness of the two drug treatments. The two treatments were; 1) a Two-Drug (paclitaxel and carboplatin) Combination Chemotherapy, and 2) a Four-Drug (methotrexate, vinblastine, asplatin, doxorubin) Combination Chemotherapy. The urothelium is the lining of the kidney, ureter, bladder, or lining of the urinary tract.

Results

The study did not show one treatment to be more beneficial than the other. Of patients receiving the four-drug combination, 12.8 percent experienced a complete response rate (no detectable cancer remaining) and 23.1 percent experienced a decrease in the size or extent of their cancer (partial response). The overall response rate was 35.9 percent. More patients experienced serious side effects while taking the four-drug combination (33 percent) than the two-drug combination (15 percent). These included nausea, vomiting, mouth sores and decreased blood cell production.

Conclusion

E4897 did not meet its accrual goal and, therefore, conclusions from the study must be viewed with caution. In the 10-year period since the trial was first planned, gemcitabine/cisplatin has become the standard up-front regimen for advanced urothelial cancer given it is likely as effective as M-VAC and somewhat less toxic. Carboplatin/paclitaxel remains a reasonable regimen for patients with renal insufficiency or somewhat poorer performance status. Chemotherapy results have likley been maximized in this disease and the next generation of studies will focus on targeted agents.

Start Date

September 1998

Stop Date

June 2001

Number of Participating Patients

85

Eligibility Requirements

Patients must have had transitional cell carcinoma of the urothelium that could be measured or evaluated and had no previous chemotherapy.

Study Design

Patients were randomly assigned to one of two groups. Patients in one group received a drug called paclitaxel, which was injected into a vein over three hours, followed by a drug called carboplatin injected similarly over 30 minutes. This treatment was repeated every three weeks for six cycles (18 weeks total) or until it was no longer effective.

Patients receiving the four-drug combination received treatment in 28-day cycles. Methotrexate was injected in a vein on days one, 15 and 22; vinblastine was injected in a vein on days two, 15 and 22; and cisplatin and doxorubin were injected in a vein on day two. This continued for six cycles (24 weeks total) or until the treatment was no longer effective. Patients in both groups were given blood tests, x-rays and scans periodically to evaluate the effect of the chemotherapy treatment on their cancer.

Side Effects

The side effects most commonly reported were lowered blood counts which increase the risk of infection, mouth sores, numbness or tingling of hands and feet, and skin rashes.

Additional Information at ClinicalTrials.gov

NCT00003376