Researchers have found that patients with an advanced form of kidney cancer, for which there is no standard treatment and a very poor prognosis, respond well to a combination of two existing anti-cancer drugs.
Dr Ramaprasad Srinivasan, head of the Molecular Cancer Therapeutics Section, Urologic Oncology Branch, of the National Cancer Institute in Maryland, USA, told the 26th EORTC-NCI-AACR 1 Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain, that the combination of bevacizumab and erlotinib produced excellent response rates with tolerable side-effects in patients with advanced papillary renal cell carcinoma (pRCC) and in patients with a highly aggressive form of pRCC called hereditary leiomyomatosis and renal cell cancer (HLRCC).
He said: “The genetic and biochemical events that lead to papillary renal cell carcinoma are different to those that lead to the more common form of kidney cancer, clear cell renal carcinoma. Treatments that are effective in clear cell RCC are not particularly effective in pRCC. Some forms of pRCC, particularly those associated with HLRCC, are characterised by altered cellular metabolism; the tumour cells obtain energy from a process called aerobic glycolysis, and they require high levels of glucose to survive. We believe the combination of erlotinib and bevacizumab may target this particular weakness, at least partly, by impairing glucose delivery to the tumour cells.”
Dr Srinivasan and researchers at the NCI Urologic Oncology Branch recruited 41 patients to a phase II clinical trial of 10 mg of bevacizumab per kg of the patient’s weight, given intravenously once every two weeks, combined with a 150 mg pill of erlotinib taken orally every day. This was continued until the disease progressed or there were unacceptable toxic side-effects. Twenty patients in the first group had advanced HLRCC and 21 patients in the second group had advanced sporadic (non-hereditary) pRCC 2. Nineteen of the patients had received at least one previous systemic therapy, such as sunitinib, that had not been successful in preventing their disease progressing.
Dr Srinivasan told the Symposium: “Almost all the patients with HLRCC responded with their tumours either shrinking or remaining stable and not progressing. There was an overall response rate of 65%, with 13 patients showing tumour shrinkage of more than 30% and seven patients with stable disease. Many of the responses were long-lasting; some of the patients have remained on the study for three years or more, which is a significant since metastatic HLRCC is uniformly fatal and patients usually die within a year or so.
“Approximately a third of the patients with sporadic pRCC showed very good partial responses, many of which were durable. There was an overall response rate of 29%, with tumours shrinking in six patients and 12 patients with stable disease.”
 EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR [American Association for Cancer Research].
 Advanced disease was defined as patients with stage 4 or metastatic disease, and patients with cancer in their lymph nodes that could not be surgically removed.