Findings from a small study suggest that treatment with the drug could make resection possible.

ORLANDO—Sunitinib may have antitumor activity against unresectable primary renal cell carcinoma (RCC), permitting resection in some patients, according to preliminary results from an ongoing phase 2 trial.

“In this small series of patients, we found that about one in five patients who had an unresectable primary tumor had a response to systemic therapy that was sufficient to allow subsequent resection,” said study investigator Brian Rini, MD, an attending physician in the Department of Solid Tumor Oncology at Cleveland Clinic in Ohio.

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“These data may help to establish a new paradigm of integrating systemic therapy and surgery in patients with advanced RCC.” Findings were presented here at the 2009 Genitourinary Cancers Symposium.

Tyrosine kinase inhibitors (TKIs) like sunitinib are approved for treating patients with metastatic RCC and have been shown to prolong survival. Several new TKIs are under investigation.

Previous studies have shown that sunitinib inhibits vascular endothelial growth factor and related receptors, with high tumor shrinkage rates in patients with metastatic RCC tumors. Reduction in size of primary RCC tumors has only been anecdotally observed, however.

Patients enrolled in this trial had histologically confirmed RCC with an unresectable primary tumor, with or without distant metastasis. All patients received 50 mg of sunitinib continuous dosing in repeated six-week cycles. Staging was performed at baseline and again after every two cycles.

A Simon two-stage design was used by the investigators to test the alternative hypothesis of conversion to resectability rate of 20% vs. the null hypothesis of 5%.

To date, 13 patients are evaluable. Their median age is 60 years, 62% are male, and 85% have distant metastases. All had unresectable primary tumors due to bulky lymphadenopathy (five patients), venous thrombosis (four patients), tumor size (two patients), or proximity to vital structures (two patients).

Lead investigator Steven Campbell, MD, PhD, professor of surgery within the Section of Urologic Oncology at the Cleveland Clinic’s Glickman Urological & Kidney Institute, said nearly all 13 patients have multiple considerations.

Three patients have undergone primary tumor resection, he noted. Viable RCC was found in all specimens, with no unexpected surgical morbidity. The median best-percentage reduction in tumor size was 11% for primary tumors (range 43% reduction to 8% increase). In addition, the median best-percentage reduction for nonprimary tumors was 16% (range 90% reduction to 29% increase). 

Two patients (15%) had an objective partial response per Response Evaluation Criteria in Solid Tumors. Ten patients have discontinued therapy (nine because of disease progression and one because of thrombocytopenia).

Seven patients (53%) have experienced grade 3 toxicity, including thrombocytopenia (four patients), fatigue (two patients), hypertension (two patients), anemia (one patient), hemoptysis (one patient), and hand-foot syndrome (one patient). One patient had grade 4 neutropenia.

“These data suggest that this approach is worth looking at, but we have not proven that this is the way to go,” Dr. Campbell said. “So now we know that sunitinib has significant activity in this setting, and it appears to be tolerated in the same way as it is in other settings. What is new here is that we found it does not prevent doing surgery safely.”