Suzanne E Patton | PubMed Health

PubMed2004

Phase II trial of combination interferon-alpha and thalidomide as first-line therapy in metastatic renal cell carcinoma.

OBJECTIVES: To present the results of a Phase II trial of thalidomide and interferon-alpha in renal cell carcinoma. METHODS: Patients with metastatic clear cell renal cell carcinoma and no prior systemic therapy were accrued. Interferon-alpha was administered at 5 million units subcutaneously three times per week. Thalidomide was started at 100 mg/day for 2 weeks and then escalated 200 mg every 2 weeks to 1000 mg or until grade 3-4 toxicity developed. Patients were assessed radiographically at baseline and after 12 weeks. Steady-state thalidomide plasma concentrations were determined. RESULTS: Thirty patients were enrolled. The median age was 62 years. Seventeen patients (57%) had undergone nephrectomy before therapy. One patient died during therapy. Of the 30 patients, 29 had at least grade 2 toxicity and 17 patients had at least grade 3. At 12 weeks, no patient had a complete response, 2 had a partial response (6.7%), 8 had stable disease (26.7%), and 11 (including 1 patient with an initial partial response) had disease progression (36.7%). Nine patients were removed from the study before 12 weeks. The median follow-up was 49.6 weeks (range 2.4 to 123.7). The median time of participation in the study was 11.1 weeks (range 1.4 to 63.9). At last follow-up, 2 patients were receiving the study therapy, 1 with stable disease at 64 weeks and 1 with a partial response at 53 weeks. The median survival was 68 weeks. A linear relationship was found between the thalidomide plasma concentration and dose. No relationship was apparent between the concentration and either treatment-related toxicity or response. CONCLUSIONS: Interferon-alpha and thalidomide as front-line therapy for metastatic renal cell carcinoma showed limited activity. The objective response rate was 7%. One third of patients experienced toxicity that required discontinuation of thalidomide. Randomized controlled studies are needed to determine any objective benefit of this regimen over either drug alone.

Adult↗

PubMed2002

Bladder cancer.

Bladder cancer is a common and chemotherapy-responsive tumor, related to tobacco smoking, environmental arsenic exposure, industrial dye exposure, and parasitic schistosomiasis exposure. Both reduction of carcinogen exposure and chemoprevention, possibly with cyclooxygenase 2 inhibitors, should reduce the incidence. The search for the ideal screening and monitoring test continues with some promising new candidates, including survivin. Although 10-year survival can be achieved in 87% of early-stage patients with muscle-invasive disease rendered T(0) and 57% of those rendered T(1) at second look after transurethral resection bladder tumor, most still require radical cystectomy. Continued improvements in surgical techniques permit gains in quality of life after the procedure. Ten-year survival can still be achieved with cystectomy in the face of grossly positive lymph nodes in 32% of T(2) and 10% of T(3) patients. A recent meta-analysis indicates that preoperative irradiation is unlikely to be beneficial, but definitive chemoradiation can produce significant 5-year survival rates in nonoperative candidates and those desiring bladder preservation. The Intergroup now has preliminary data from a Southwest Oncology Group-based trial showing a significant benefit for neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin. The regimen of gemcitabine and cisplatin is equally efficacious with less toxicity than methotrexate, vinblastine, doxorubicin, and cisplatin. It has been adopted as the standard arm in a phase III trial for advanced bladder cancer, comparing it with the triplet of gemcitabine, paclitaxel, and cisplatin. Other active agents in bladder cancer include ifosfamide, carboplatin, docetaxel, and vinorelbine, and various doublets of these agents are being tested in phase II trials, with promising results.

Antineoplastic Agents↗