63

Treatment of Advanced Renal Cell

Carcinoma

W. Marston Linehan; Ramaprasad Srinivasan

Questions

1.What is the approximate overall objective response rate to interleukin-2 (IL-2) monotherapy in patients with metastatic renal cell carcinoma (RCC)?

a.5%

b.10%

c.15%

d.25%

e.35%

2.Which of the following regarding IL-2 therapy for metastatic RCC is TRUE?

a.IL-2 has demonstrable efficacy in clear cell as well as papillary RCC.

b.Randomized studies have demonstrated a survival benefit associated with high-dose IL-2.

c.Low-dose subcutaneous and high-dose intravenous IL-2 have comparable efficacy.

d.Durable complete responses are seen in a small proportion of patients receiving high-dose IL-2.

e.Newer formulations have led to better tolerability of high-dose IL-2.

3.In the Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic scheme for patients with metastatic RCC undergoing therapy with cytokine or chemotherapy, which of the following is NOT a predictor of poor outcome?

a.Karnofsky performance status greater than 80%

b.Elevated lactate dehydrogenase

c.Elevated calcium

d.Decreased hemoglobin

e.Absence of prior nephrectomy

4.In which of the following patients with metastatic RCC is cytoreductive nephrectomy most appropriate?

a.A 50-year-old male with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, a large 12-cm right renal mass, and four small pulmonary metastases

b.A 67-year-old female with an ECOG performance status of 0, a 7-cm left renal mass, retroperitoneal adenopathy, and hepatic metastases that have doubled in size over 4 weeks

c.An 81-year-old man with an asymptomatic 6-cm right renal mass and multiple hepatic metastases who has declined systemic therapy

d.A 72-year-old man with an ECOG performance status of 2, a 5-cm right renal mass, and mild dyspnea associated with numerous pulmonary metastases

5.The rationale for cytoreductive nephrectomy followed by immunotherapy with cytokines in patients with synchronous metastatic RCC includes all of the following EXCEPT:

a.removal of tumor burden.

b.removal of source of tumor-associated immunosuppressive factors.

c.reversal of acquired immune dysfunction.

d.improved tolerance to cytokine therapy.

e.improved T-lymphocyte function.

6.Which of the following statements about cytokine therapy for metastatic renal cell carcinoma is TRUE?

a.Lymphokine-activated killer (LAK) cells augment the efficacy of both interferon-α (IFN-α) and IL-2.

b.Randomized trials have demonstrated a significant survival advantage for combined IL-2 and interferon versus either agent given as monotherapy.

c.The combination of IL-2 and interferon leads to higher overall response rates than either agent alone.

d.The complete response rate with interferon-α monotherapy is 10%.

7.Which of the following metastatic RCC tumors is most likely to benefit from cytokine therapy?

a.Papillary carcinoma

b.Clear cell carcinoma

c.Medullary carcinoma

d.Collecting duct carcinoma

e.Chromophobe carcinoma

8.A 58-year-old woman had a nephrectomy 6 years previously for a grade 2 clear cell carcinoma. She was incidentally found to have three left-sided pulmonary nodules (two < 1.0 cm, other 2.5 cm). A physical examination is normal, as are all blood chemistries. Computed tomography (CT) of the brain, lungs, abdomen, and pelvis show three pulmonary nodules with no associated hilar or mediastinal adenopathy, and a bone scan is normal. Which of the following is the most appropriate next step in her management?

a.Therapy with high-dose IL-2

b.Biopsy of a pulmonary nodule

c.Mediastinoscopy followed by resection of the pulmonary nodules

d.Observation

e.IFN-α therapy

9.The sirolimus analogues temsirolimus and everolimus act primarily on which of the following pathways?

a.vascular endothelial growth factor (VEGF)

b.Platlelet-derived growth factor (PDGF)

c.Raf-1

d.mechanistic target of rapamycin (mTOR)

e.c-met

.The overall RECIST response rate in metastatic clear cell RCC patients receiving front-line therapy with sunitinib is:

a.15% to 20%.

b.30% to 40%.

c.60% to 70%.

d.less than 10%.

e.greater than 70%.

.In patients with previously untreated metastatic clear cell RCC, sunitinib is:

a.associated with a higher response rate compared with interferon-α.

b.associated with a longer progression free survival compared with interferon-α.

c.associated with a better quality of life compared with interferon-α.

d.all of the above.

e.none of the above.

.Which of the following agents has been shown to prolong progression-free survival in patients with metastatic clear cell RCC who have progressed on first-line therapy with VEGFR antagonists?

a.Axitinib

b.Bevacizumab + interferon-α

c.High-dose IL-2

d.Everolimus

e.Low-dose subcutaneous IL-2

.Randomized trials in patients with previously untreated metastatic clear cell RCC have demonstrated that sorafenib is:

a.associated with better overall survival compared with interferon-α.

b.associated with a longer progression free survival compared with interferon-α.

c.associated with a better quality of life compared with interferon-α.

d.all of the above.

e.none of the above.

.Which of the following agents has been shown in randomized phase 3 trials to prolong survival in “poor risk” metastatic RCC patients?

a.IL-2

b.Sunitinib

c.Sorafenib

d.Temsirolimus

e.IFN-α

.Which of the following molecules is NOT known to be upregulated as a consequence of VHL dysfunction?

a.VEGF

b.PDGF

c.TGF-α

d.Glut-1

e.Raf-1

.In what proportion of sporadic clear cell tumors are mutations or promoter hypermethylation of the VHL gene seen?

a.70% to 90%

b.10% to 20%

c.100%

d.Less than 10%

.A 47-year-old man presents with multiple metastatic lesions to the lungs and liver 8 months following a radical nephrectomy for a 9-cm papillary type I renal tumor. Which of the following statements about his systemic treatment options is TRUE?