Unresectable Renal Cell Carcinoma Research Articles

883 POSTER Phase I trial of sorafenib (BAY 43–9006) in combination with interferon alpha-2a in patients with unresectable and/or metastatic renal cell carcinoma and malignant melanoma

883 POSTER Phase I trial of sorafenib (BAY 43–9006) in combination with interferon alpha-2a in patients with unresectable and/or metastatic renal cell carcinoma and malignant melanoma

Prognostic evaluation of transcatheter arterial embolization for unresectable renal cell carcinoma with distant metastasis.

To evaluate the efficacy of transcatheter arterial embolization (TAE) in patients with unresectable renal cell carcinoma (RCC) and distant metastasis at the time of diagnosis. The study included 54 patients with histologically defined RCC (by biopsy in 28 and autopsy in 26) who were unable to undergo nephrectomy mainly because their performance status was poor (score > or = 2). The patients were classified into two groups; 24 patients who underwent TAE with ethanol and 30 patients who did not. The two groups were compared for several clinical factors, mainly focusing on the prognosis. There were no significant differences in the clinical factors, including performance status, tumour diameter, vascular invasion, lymph node involvement, adjuvant therapy, metastatic organs or the number of metastases between the groups. However, the proportion of patients with para-neoplastic signs in those undergoing TAE was greater than that in those not, and the difference was significant (chi squared 0.35, P < 0.05). The median survival of the two groups was 229 days (TAE) and 116 days (no TAE). The 1-, 2- and 3-year survival rates in the TAE group were 29%, 15% and 10%, respectively, and in those not undergoing TAE were 13%, 7% and 3%, respectively. Those undergoing TAE had a significantly better prognosis than those who did not (P = 0.019). The adverse effects in patients undergoing TAE with ethanol included fever, back pain on the affected side, nausea and vomiting, but all the patients recovered from these adverse effects. TAE with ethanol is a safe and effective treatment for patients with unresectable disseminated RCC and a poor performance status; TAE with ethanol not only induces ablation of the primary tumour, but also prolongs survival.

Transcatheter arterial embolization of unresectable renal cell carcinoma with a mixture of ethanol and iodized oil

The effectiveness of renal transcatheter arterial embolization (TAE) with a mixture of ethanol and iodized oil (Lipiodol) was analyzed retrospectively in 27 patients with unresectable renal cell carcinoma. Symptomatic or permanent palliation by TAE was performed with the intent to achieve total or partial ablation of the kidney with 10-28 ml of embolic material in a 3:1 mixture of ethanol and iodized oil. Clinical, angiographic, and computed tomographic (CT) follow-up were analyzed. Cumulative survival was estimated with the Kaplan-Meier method. Partial (5) or complete (22) ablation of the embolized kidneys was achieved in all cases. Follow-up CT after 1 month revealed Lipiodol uptake in the tumor area (14/14), decreased size of the tumor (6/14), and gas formation (7/14). Pulmonary metastasis improved significantly in one patient after transcatheter arterial embolization and adjunctive chemotherapy. Overall median survival of the 27 patients was 8.5 months. The median survival was 23 months in 10 patients with stage III, three of whom are still alive, and was 7 months in 15 patients with stage IV tumors. The mixture of ethanol and Lipiodol is not only a convenient embolic material to use, but is also effective for selective or nonselective devascularization for unresectable renal cell carcinoma.

Therapy of renal cell carcinoma with interleukin-2 and lymphokine-activated killer cells: phase II experience with a hybrid bolus and continuous infusion interleukin-2 regimen.

Forty-seven patients with metastatic or unresectable renal cell carcinoma were treated with interleukin-2 (IL-2) and lymphokine-activated killer (LAK)-cell therapy, using a hybrid IL-2 regimen. IL-2 was administered initially by intravenous bolus (10(5) U/kg [Cetus Corp, Emeryville, CA] every 8 hours for 3 days) during the priming phase, and subsequently by continuous infusion (3 x 10(6) U/m2 for 6 days); during this second treatment period, in vitro-generated LAK cells were administered. Despite selection of patients for good performance status (PS) (29, PS 0; 18, PS 1) prior nephrectomy (43 of the 47 patients), and low tumor burden, the response rate was low (two complete [CRs] and two partial responses [PRs], for an overall objective response rate of 9%). Toxicity was comparable to that experienced with the high-dose bolus regimen. These results suggest that the dose and schedule of IL-2 administration may influence the likelihood of response to IL-2 in renal cell carcinoma.

A phase II clinical trial of adoptive immunotherapy for advanced renal cell carcinoma using mitogen-activated autologous leukocytes and continuous infusion interleukin-2.

Forty patients with metastatic, recurrent, or unresectable renal cell carcinoma were entered into a study of the therapeutic efficacy of adoptive immunotherapy using periodate (IO4-) and interleukin-2 (IL2)-activated autologous leukocytes and continuous infusion low-dose IL2. Patient survival was also examined. The first 15 consecutive patients were enrolled in protocol A without an IL2 priming phase and the following 25 patients were entered in protocol B where a 5-day priming phase was initiated before leukapheresis. A maintenance regimen consisted of either 3 x 10(6) units of recombinant interferon-alpha (rIFN-alpha), three times per week only or together with leukapheresis and infusion of IO4-/IL2-activated cells and 2 days of continuous infusion IL2 per month. Thirty-four patients completed the protocol treatment. Four patients were removed from the study owing to rapid tumor progression and two patients died while receiving treatment. The clinical response rate was 22%: two patients had a complete response and five patients had a partial response. Among the 25 patients who had no clinical response, 11 patients had either a mixed response or stabilization. Neither response, response duration, nor site response correlated with the total dose of IL2 administered or the number of activated killer cells infused. Patients who received maintenance therapy had longer survival times than patients who did not receive such therapy. All toxicity and side effects associated with IL2 treatment were transient and resolved after discontinuation of the drug. Patients on maintenance therapy tolerated both rIFN-alpha and monthly infusions of activated killer cells and IL2 well. This study confirms the concept of adoptive immunotherapy as a new treatment approach for advanced renal cell carcinoma and suggests that maintenance therapy may prolong survival time.