Prolonged response to cytoreductive surgery and Sunitinib in an elderly patient with synchronous multiple metastases from renal cell carcinoma

Renal cell carcinoma (RCC) is a cancer with a relatively low incidence, accounting for about 2-3% of all cancer cases. Multitargeted therapy of advanced RCC appears to be a better option than immunotherapy. Sunitinib is a multitarget tyrosine kinase inhibitor whose activity has been demonstrated in phase III and expanded-access studies. In the present paper, we report the case of an elderly patient with multiple metastases who attained a prolonged response to sunitinib. A 72-year-old woman with a Karnofsky performance status of 90, no significant medical history, and no comorbidities except hypertension treated with transdermal clonidine (TTS-1) was referred to our hospital in October 2006 complaining of flank pain and gross hematuria. At clinical examination, a mass in the right flank and a 2 cm subcutaneous nodule in the right breast were detected. Total-body computed tomography (CT) scan showed a right kidney neoplasm of 15 cm, a mass in the left adrenal gland, peripancreatic abnormal tissue, small lung nodules (three bilateral nodules of 1 cm) and extensive hilarmediastinal lymphadenopathies (maximum diameter 3.8 cm). At cranial CT evaluation, a sub-centimetric (0.4 cm) thalamic lesion of uncertain etiology was identified. Bone scintigraphy was normal. At blood chemistry assay, mild anemia (Hb 11.7 g/dl) was present; LDH and calcium were in the normal range. Surgical excision of the subcutaneous breast nodule revealed an adenocarcinoma of metastatic origin. The patient underwent a right radical nephrectomy and abdominal cytoreductive surgery, including left adrenalectomy and distal pancreatectomy. No residual intra-abdominal gross tumor remained after surgery. Final pathology documented a 15×10×8 cm clear cell RCC, Fuhrman grade 2, pT3cN0M1, with pancreatic and contralateral adrenal involvement. After surgery, the patient recovered quickly and was placed on long-term corticosteroid treatment. Four weeks later (December 2006), she began subcutaneous interferon-alpha (IFN) 6 MU three times/weekly; higher doses were not tolerated. In February 2007, treatment was discontinued because of malaise and bone pain in the left hip. A CT scan of the pelvis revealed bone involvement of the left ischium. On CT and MRI, the thalamic lesion was found to have increased to 1 cm, with peripheral edema. The patient underwent stereotactic radiosurgery (Cyberknife) of the brain lesion. After cardiological assessment with ECG and echocardiography, in April 2007, she was placed on 50 mg sunitinib daily in a six-week cycle according to a 4/6 schedule (four weeks on treatment, two weeks off treatment. Up to June 2010, the patient was continuing sunitinib treatment and there was good control of arterial blood pressure with the three-drug combination, no electrocardiographic or echocardiographic alterations, normal thyroid function, grade 1 leukopenia and thrombocytopenia, and macrocytosis. The patient was in good performance status (Karnofsky 80) and was asymptomatic, but complaining of asthenia, especially during the four weeks of sunitinib administration, causing mild impairment of quality of life. The role of surgery in metastatic RCC is still debatable especially in this new era of targeted therapy. In conclusion, in the treatment of older people with targeted therapies, the following recommendations are made: assessment of the type and severity of co-morbidities; careful monitoring of cardiac, thyroid and metabolic dysfunctions, and assessment of the impact of every kind and grade of the developed toxicities on quality of life. 1 Flanigan RC, Mickisch GH, Sylvester R, Tangel C, Van Poppel H and Crawford ED: Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis. J Urol 171: 1071-1076, 2004. 2 Hofmann HS, Neef H, Krohe K, Andreev P and Silber RE: Prognostic factors and survival after pulmonary resection of metastatic renal cell carcinoma. Eur Urol 48: 77-81, 2005. 3 Karellas ME, Jang TL, Kagiwada MA, Kinnaman MD, Jarnagin WR and Russo P: Advanced-stage renal cell carcinoma treated by radical nephrectomy and adjacent organ or structure resection. BJU Int 103: 160-164, 2008.