This launch issue of Renal Cell Cancer Update includes interviews with three clinical investigators and a tumor panel discussion in which four community-based medical oncologists present cases from their practices that typify the dilemmas facing docs who deal with this somewhat uncommon and highly frustrating malignancy. These cases, which are summarized below, illuminate the rapidly changing algorithm of clinical care for the disease, and of particular interest is the use and selection of the new multikinase inhibitors (MKIs), sorafenib and sunitinib.

Case 1: A 59-year-old man presented to a podiatrist with pain in his right foot, and biopsy revealed a 4.5-cm clear cell carcinoma to the right metatarsal. Subsequent CT scans demonstrated a 6.6-cm mass in the left kidney, with no other evidence of disease. The patient was treated with surgical removal of the primary tumor and the metastasis. After several years with no evidence of disease progression, he was diagnosed first with one and then a second isolated adrenal metastasis, which were surgically extirpated. He has not received systemic therapy.

This case history would be unusual for most solid tumors, but it is common in renal cell cancer. With the emergence of the MKIs, which are significantly less toxic than prior available systemic agents, one wonders if the progression of cases like this one could be slowed by an anti-angiogenic strategy.

Case 2: A 63-year-old man underwent a nephrectomy for a 4.8- x 4.1-cm moderately differentiated clear cell carcinoma with negative nodes and no capsular invasion. After seven months, the patient developed asymptomatic bilateral lung nodules and a right paratracheal lymph node.

This patient’s rapid recurrence after the initial resection places him in a poor-risk category, raising an important question: Assuming it becomes available in the United States, should the mTOR inhibitor temsirolimus (CCI-779 for the diction challenged) be considered? In this instance, the patient received sorafenib on a clinical trial and had a response lasting 14 months. The patient is currently receiving sunitinib. This case demonstrates two important points:

1. Several small case series have clearly documented sequential responses to MKIs.
   
2. This man entered a double-blind trial of sorafenib versus placebo. After a couple of months of treatment, the patient, who was randomly assigned to the sorafenib arm, was very concerned that he was receiving a placebo due to a lack of toxicity. This story would not have been told of interferon or interleukin.

Cases 3A and 3B:

3A: A 61-year-old man with a 2-cm mass in the right kidney underwent a right partial nephrectomy, which revealed a Grade I clear cell carcinoma with negative margins. No other evidence of disease appeared on CT scans. Ten months later, the patient developed a 2- x 1-cm right upper lobe lesion of the lung, which was surgically resected.

3B: A 63-year-old woman presented with voiding difficulties and hematuria. A CT scan revealed a 4-cm mass in the right kidney, and she underwent radical nephrectomy, which demonstrated clear cell histology with some papillary features and no lymphovascular invasion.

A new Intergroup adjuvant trial will compare sorafenib, sunitinib and placebo, but is there currently a role off protocol for adjuvant therapy or treatment of Stage IV NED with these agents?

Case 4: A 74-year-old man presented with bilateral renal masses on ultrasound. Biopsy revealed clear cell carcinoma, and the patient underwent a laparoscopic cryosurgical ablation of the smaller lesion followed by radical nephrectomy to remove the other tumor. Pathology confirmed a 7-cm clear cell carcinoma confined to the kidney with negative nodes.

Nephron-sparing surgery includes many creative options, as demonstrated by this case. However, the challenge of administering antitumor agents to patients with renal and/or hepatic dysfunction is accentuated by the modest available clinical trial data attempting to answer this question.

Case 5: A 63-year-old man presented with a two-month history of malaise, loss of appetite and right upper-quadrant discomfort. CT revealed an enlarged liver with probable metastatic disease and an 8-cm right kidney mass. Liver biopsy revealed a moderately differentiated papillary carcinoma of presumed renal origin.

Although the clinical research database on clear cell cancer is significant and growing, minimal data are available to guide decision-making for less common tumors such as papillary and collecting duct cancers.

The encouraging recent results of anti-angiogenic therapies such as the MKIs and bevacizumab seem understandable in view of the long-known “bloody” nature of renal cell cancer. Fortunately, these interventions, along with other targeted approaches such as CCI-779, have the potential to alter the natural history of this disease and to provide clinicians the artillery to more effectively manage cases like those presented on this program.

— Neil Love, MD
NLove@ResearchToPractice.net
July 25, 2006

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Editor’s Note:
Renal cell fireworks

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Nicholas J Vogelzang, MD
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Ronald M Bukowski, MD
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Janice P Dutcher, MD
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