Current status of the therapy of advanced renal carcinoma

Abstract

A preclinical murine renal model system is available for evaluation of the effectiveness of therapeutic agents. Clinical review reveals that objective response rates to hormonal agents reported since 1971 have been substantially lower than those reported prior to 1971. Many chemotherapeutic agents have not been adequately evaluated clinically or with the experimental model. Vinblastine to date may be the most active single agent with a 25% objective response rate. At the present time, it is uncertain whether combination chemotherapy or hormonal chemotherapy add to response rates obtained with single agents. There is some evidence that immunotherapy may be of some adjuvant benefit and, thus may provide an additional avenue of investigation.

In vitro sensitivity testing of human renal cell carcinoma with cytostatic agents and interferon alpha-2a

“…Numerous drugs have been administered as single agents predominantly vinblastine nowadays [2,3]. Hrushesky and Murphy reported a 25 % objective response, superior to any other single agent or combination therapy [ 14], which was also confirmed by other investigators [3,13]. The interferons represent glycoproteins produced by human cells in response to viral infections as well as various other inducers.…”

The Medical Treatment of Metastatic Renal Cell Cancer

“…This in part appears to be due to the over expression of multi-drug resistant 1 (MDR1) and/or multi-drug resistance-associated protein (MRP) genes (Yu et al 1998, [10]). In 1977 Hrushesky and Murphy [11] reported a 25% objective response achieved by vinblastine as the most effective single agent then currently available. This study has not been reproduced elsewhere and the objective responses both complete and partial to chemotherapy alone have tended to be less than 10%.…”

Combination of Recombinant Interferon Alpha-2A and Vinblastine in Advanced Renal Cell Cancer

“…Whether a given IFN preparation wall prove more active than others is not clear, since the range of reported response rates for various studies with HuIFN-alpha (Le), HuIFN-alpha (Ly), and recombinant IFN-alpha is essen tially identical [10]. In vitro data suggest synergistic activity of HuIFN-alpha (Le) and vinblastine in a human tumor stem cell assay [11], and that vinblastine alone has antitumor activity in a small number of patients w'ith RCC [12], Figlin et al [13] used this combination to treat patients with advanced RCC. Therapeutic responses were seen with this combination.…”

“…Therefore, it appears necessary that further experience is gained for the optimal administration of r-IFN in well-controlled phase II trials. For this reason we instituted a multicenter phase II trial of IFN-alpha 2a plus vinblastine w'ith the regimen used in different trials [12,16,17] to study the efficacy and toxicity of this combination.…”