Renal cancer accounts for about 3% of all solid tumours, and its incidence is rising.1-3 Regionally advanced or metastatic cases account for approximately half of new cases. The management of metastatic renal cancer remains a therapeutic challenge. At the point of diagnosis with metastatic disease, the low response rates (15% to 20%) and even lower cure rates (6% to 8%) of current therapies are discouraging.Factors such as age, co-morbidities, heterogeneous histologies, and especially the potential for a slow natural history can complicate the decision of whether to treat the cancer or to pursue a supportive, symptom directed approach. The histologic subtype of the cancer has an impact on the chance of response. For instance, the only histologic subtype that appears to respond to immune-directed approaches with any consistency is the clear cell subtype. Variants such as granular cell, papillary, or sarcomatoid appear more consistently refractory to the immune approach. Fortunately, clear cell is the most common subtype, accounting for approximately 70% of cases. Earlier successes in applying the immune approach to the problem, as well as the limited contributions from conventional cytotoxic drugs, have helped to make metastatic renal cell cancer a focus for contemporary development of novel immunotherapy.
Before the advent of targeted therapy for RCC, the mainstay of treatment for patients with metastatic disease was immunotherapy with IL-2 or IFN-α. There is a strong rationale for using immunotherapy in patients with RCC. The anecdotal observations of spontaneous remissions of advanced RCC and infiltration of cancer tissue by tumour-specific immune cells, for example, suggest that immune mechanisms play a role in the natural disease course of RCC.
Findings of a phase II study evaluating, a dendritic cell-based vaccine, administered in combination with sunitinib demonstrated improvement in median overall progression-free survival in newly diagnosed patients with mRCC (11.9 months for combination therapy versus 8 months for historical data with sunitinib alone) . No additive toxicity of the two agents was observed; the majority of adverse events (AEs) were mild injection site reactions. A phase III study to evaluate Dendritic cell based vaccine plus sunitinib in patients with newly diagnosed advanced RCC undergoing nephrectomy is planned.