Immunochemotherapy for Metastatic Renal Cell Carcinoma
Immunochemotherapy for Metastatic Renal Cell Carcinoma
Immunochemotherapy consisting of IL-2, INF-A, and VBL and 5FU is regarded as the treatment of
 choice in metastatic renal cell carcinoma. During the period 1996-2000, we evaluated the
 efficacy and toxicity of this immunochemotherapy, combined with an aggressive surgical
 approach: nephrectomy before treatment and resection of residual disease. The 3-year survival
 rate for the entire group and complete responder patients was 30% and 88%, respectively. The
 side effects were usually moderate and consisted mainly of a flu-like syndrome, headache,
 nausea, vomiting and depression. Most importantly, there was no drug-related death. Good
 performance status, absence of bone metastases and prior nephrectomy were associated with
 higher response rates.

 Capecitabine is a novel fluoropyrimidine carbamate, orally administered and selectively
 activated to Fluorouracil by a sequential triple-enzyme pathway in liver and tumor cells.
 Capecitabine at dose of 2,500mg/m2/d divided equally into two daily doses for 14 days in
 patients who failed to respond to "standard" immunotherapy achieved a 30% objective response.
 Toxicity consisted of hand-foot syndrome.

 Aim of Study:

 To evaluate efficacy and toxicity of the combination of IL-2, INF-A, VBL and Capecitabine in
 MRCC
This is a phase II study, non-randomized in patients with metastatic renal cell carcinoma.
 The treatment will include: Proleukin (produced by Chiron and supplied by Megapharm Israel
 Ltd), Roferon A and Xeloda (produced by Roche) and VBL. The treatment will be given in 8-week
 courses with an interval of two weeks of rest in which the response (on D63) and toxicity
 will be assessed.

 45 patients with MRCC will be entered into this study during a 18-month period. All patients
 must meet all inclusion and exclusion criteria. All data of each participating patient,
 including medical history, disease characteristics, laboratory and imaging tests, response
 and toxicity to treatment will be entered into the specific form before, during, after each
 treatment course and during follow up.

 Patients will be followed up for survival status and disease status every 6 months until last
 visit or death.

 Treatment Schedule:

 Proleukin S.C. 10X106 IU/m2 three times a week (Sun, Tue, Thu), weeks 1 - 4 Roferon A S.C. 6
 X 106 IU/m2 once a week (Wed), weeks 1 - 4 Roferon A S.C. 3 X 106 IU/m2 three times a week,
 weeks 5 - 8 Xeloda Oral 1,000 mg/m2 twice a day, weeks 5, 6 Vinblastine I.V. 4mg/m2, Day 1,
 weeks 5 &
Inclusion Criteria:

 - Inclusion Criteria; Patients with the following criteria will be included in this study

 -  Pathological (histology or cytology) diagnosis of renal cell carcinoma

 -  Clinical evidence of metastatic disease

 -  Performance status 0 - 2 (European Cooperative Oncology Group Score)

 -  Nephrectomy before starting treatment

 -  Normal cardiac function (left ventricular ejection fraction >45%).

 -  Normal blood counts: WBC >3,000/ml3, Hb >10gr%, Platelets >100,000/ml3

 -  Normal kidney function: Creatinine <1.3 mg/dl

 -  Age  18 years

 -  Patient's written consent (on informed consent form)

 Exclusion Criteria:

 -  Life expectancy less than 3 months

 -  Brain metastases

 -  Ischemic heart disease - active

 -  Prior immunochemotherapy

 -  Performance status 3 or more (European Cooperative Oncology Group Score)

 -  Schizophrenia

 -  Active liver disease