Risk Factor Criteria

Memorial Sloan–Kettering Cancer Center (MSKCC) and Cleveland Clinic Foundation (CCF) Risk Factor Criteria for Advanced RCC

• According to the prognostic model proposed by Motzer et al, patients with advanced RCC may be defined as favorable, intermediate, or poor risk, depending on the presence or absence of 5 distinct risk factors¹
• Mekhail et al validated the Motzer et al data and identified additional independent prognostic factors in the survival of patients with previously untreated metastatic RCC.² Note: patient populations may have received different therapies prior to the analysis
• The CCF criteria proposed by Mekhail et al differs from the MSKCC criteria proposed by Motzer et al as follows^1,2:
  • Performance status was not identified as a prognostic risk factor
  • Expanded prognostic risk factors included prior radiotherapy and the presence of hepatic, lung, or retroperitoneal nodal metastases
  • The number of metastatic sites can be used as a surrogate for individual sites

MSKCC Criteria 20021 Prognostic Factor
Karnofsky performance status	< 80
Time from diagnosis to treatment with IFN-α	< 12 months
Hemoglobin	< Lower limit of laboratory’s reference range
Lactate dehydrogenase	> 1.5 x the upper limit of laboratory’s range
Corrected serum calcium	> 10.0 mg/dL

CCF Criteria 20052 Prognostic Factor
Time from diagnosis to study entry	< 12 months
Hemoglobin	< Lower limit of laboratory’s reference range
Lactate dehydrogenase	>1.5 x the upper limit of laboratory’s reference range
Corrected serum calcium	>10 mg/dL
Prior radiotherapy	Yes
Presence of hepatic, lung, or retroperitoneal lymph node metastases	2 or 3 sites

Risk Groups	MSKCC Criteria (2002)1 Median OS	CCF Criteria (2005)2 Median OS
Favorable	29.6 months	26.0 months
Intermediate	13.8 months	14.4 months
Poor	4.9 months	7.3 months
	Risk groups defined as	Risk groups defined as
	Favorable: 0 risk factors Intermediate: 1 or 2 risk factors Poor: 3, 4, or 5 risk factors	Favorable: 0 to 1 risk factor Intermediate: 2 risk factors Poor: more than 2 risk factors

Read the full Journal of Clinical Oncology article Validation and Extension of the Memorial Sloan-Kettering Prognostic Factors Model for Survival in Patients With Previously Untreated Metastatic Renal Cell Carcinoma.

Guidelines for Kidney Cancer Treatment

For more information and guidelines on kidney cancer treatment, visit the National Comprehensive Cancer Network (NCCN) Web site and click on “NCCN Clinical Practice Guidelines in Oncology.”

Important Safety Information

Important Safety Information

• Hypersensitivity reactions manifested by symptoms, including, but not limited to anaphylaxis, dyspnea, flushing, and chest pain have been observed with TORISEL.
• Serum glucose, serum cholesterol, and triglycerides should be tested before and during treatment with TORISEL.
  • The use of TORISEL is likely to result in hyperglycemia and hyperlipemia. This may result in the need for an increase in the dose of, or initiation of, insulin and/or oral hypoglycemic agent therapy and/or lipid-lowering agents, respectively.
• The use of TORISEL may result in immunosuppression. Patients should be carefully observed for the occurrence of infections, including opportunistic infections.
• Cases of interstitial lung disease, some resulting in death, have occurred. Some patients were asymptomatic and others presented with symptoms. Some patients required discontinuation of TORISEL and/or treatment with corticosteroids and/or antibiotics.
• Cases of fatal bowel perforation occurred with TORISEL. These patients presented with fever, abdominal pain, metabolic acidosis, bloody stools, diarrhea, and/or acute abdomen.
• Cases of rapidly progressive and sometimes fatal acute renal failure not clearly related to disease progression occurred in patients who received TORISEL.
• Due to abnormal wound healing, use TORISEL with caution in the perioperative period.
• Patients with central nervous system tumors (primary CNS tumor or metastases) and/or receiving anticoagulation therapy may be at an increased risk of developing intracerebral bleeding (including fatal outcomes) while receiving TORISEL.
• Live vaccinations and close contact with those who received live vaccines should be avoided.
• Patients and their partners should be advised to avoid pregnancy throughout treatment and for 3 months after TORISEL therapy has stopped.
• The most common (incidence ≥30%) adverse reactions observed with TORISEL are: rash (47%), asthenia (51%), mucositis (41%), nausea (37%), edema (35%), and anorexia (32%). The most common laboratory abnormalities (incidence ≥30%) are anemia (94%), hyperglycemia (89%), hyperlipemia (87%), hypertriglyceridemia (83%), elevated alkaline phosphatase (68%), elevated serum creatinine (57%), lymphopenia (53%), hypophosphatemia (49%), thrombocytopenia (40%), elevated AST (38%), and leukopenia (32%).
• Most common grades 3/4 adverse events and laboratory abnormalities included asthenia (11%), dyspnea (9%), hemoglobin decreased (20%), lymphocytes decreased (16%), glucose increased (16%), phosphorus decreased (18%), and triglycerides increased (44%).
• Strong inducers of CYP3A4/5 (eg, dexamethasone, rifampin) and strong inhibitors of CYP3A4 (eg, ketoconazole, atazanavir) may decrease and increase concentrations of the major metabolite of TORISEL, respectively. If alternatives cannot be used, dose modifications of TORISEL are recommended.
• St. John’s Wort may decrease TORISEL plasma concentrations, and grapefruit juice may increase plasma concentrations of the major metabolite of TORISEL, and therefore both should be avoided.
• The combination of TORISEL and sunitinib resulted in dose-limiting toxicity (Grade 3/4 erythematous maculopapular rash, and gout/cellulitis requiring hospitalization).

Please see the full Prescribing Information for TORISEL.

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