A Phase II Trila of Sunitinib Schedule 4/2 vs. Shedule 2/1 as First Line Therapy in Metastatic Renal Cell Carcinoma.

A Randomized Phase II Trila of Sunitinib Four-weeks on/Two-weeks Off Versus Two-weeks on/One-week Off as First Line Therapy in Metastatic Renal Cell Carcinoma.

Sunitinib given at 50 mg/day on schedule 4/2 (4 weeks on treatment, 2 weeks off) is the standard care for first-line treatment of metastatic renal cell carcinoma, but the schedule was reported with a high rate of dose reduction and dose discontinuation because of the safety profile. So investigators conducte this randomized, multi-center phase II study to determine whether a sunitinib regimen of 50 mg/day 2-weeks on/1-week off could provide the same efficacy in terms of progression-free survival, objective response, and overall survival, while reducing drug-related toxicity.

Sunitinib given at 50 mg/day on schedule 4/2 (4 weeks on treatment, 2 weeks off) is the standard care for first-line treatment of metastatic renal cell carcinoma, but the schedule was reported with a high rate of dose reduction and dose discontinuation because of the safety profile. Sunitinib 50mg/day on schedule 2/1 (2 weeks on treatment, 1 weeks off) was reported to be associated with significantly decrease toxicities in patients who initially experienced grade 3 or greater toxicity on the schedule 4/2 and could extend treatment duration considerably. Through this research, we would like to explore whether the schedule 2/1 of sunitinib 50 mg/day as first line therapy could provide the same efficacy as standard schedule 4/2 in terms of progression-free survival, objective response, and overall survival, while reducing drug-related toxicity in metastatic renal cell carcinoma patients.

Inclusion Criteria:

• Age≥18 years, ≤75 years, male or female
• Advanced renal cell carcinoma is diagnosed histologically or pathologically
• Treatment naive at diagnosed
• At least one measurable tumor lesion (Response Evaluation Criteria In Solid Tumors)
• Eastern Cooperative Oncology Group（ECOG) performance scale is 0 or 1
• The expected life span is ≥12 weeks
• No contraindications for targeted therapy, with enough liver function and renal function and normal ECG recording Peripheral hemogram: neutrophil≥1.5×109/L, Plt≥100×109/L, Hgb≥90g/L Renal function: serum creatinine≤1.5 folds the upper limit of normal (ULN) For patients with non-metastatic liver dysfunction:alanine aminotransferase and aspartate aminotransferase≤2.5 ULN, For patients with metastatic liver dysfunction: alanine aminotransferase and aspartate aminotransferase≤5 ULN
• The patients participate voluntarily and have signed the informed consent form

Exclusion Criteria:

• Patients who have received any systemic therapy including targeted therapy,immunotherapy,chemotherapy etc at diagnosed.
• Pregnant and lactating women, or female patients of child-bearing age without taking contraceptive measures
• Patients with severe acute infection without being controlled effectively or having pyogenic and chronic infections with persistently unhealed wounds
• Past history of serious heart diseases, including: cardiac function classification ≥NYHA class II, unstable angina pectoris, myocardial infarction, arrhythmia requiring anti-arrhythmic drug therapy (excluding β-blockers or digoxin), and uncontrolled hypertension
• Patients with a history of HIV infection or active phase of chronic hepatitis B/C
• negative imaging examination result 4 weeks prior to enrollment)
• Epilepsy patients requiring drug therapy (e.g. steroids or antiepileptic drugs)
• A history of allogeneic organ transplantation