Doxorubicin and Gemcitabine in Treating Patients With Locally Recurrent or Metastatic Unresectable Renal Cell Carcinoma

OBJECTIVES:

• Determine the response rate of patients with locally recurrent or metastatic unresectable renal cell cancer with sarcomatoid features treated with doxorubicin and gemcitabine.
• Determine the progression-free survival and overall survival of patients treated with this regimen.
• Determine the toxic effects of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive doxorubicin intravenously (IV) and gemcitabine IV over 30 minutes on day 1. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 2- or 3-10 or pegfilgrastim SC on day 2. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.

After 6 courses, patients undergo a MUGA scan. Patients with a stable* left ventricular ejection fraction (LVEF) continue therapy as above. Patients who reach a total doxorubicin dose of 450 mg/m^2 and are found to have unstable cardiac function or who have an abnormal LVEF continue therapy with gemcitabine alone.

NOTE: *Stable cardiac function is defined as no decrease more than 15% of LVEF in absolute number and LVEF at least 35% in total function by MUGA.

Patients are followed every 3 months for 2 years and then every 6 months for 1 year.

ACTUAL ACCRUAL: A total of 39 patients were accrued for this study.

Inclusion criteria

• Histologically confirmed renal cell carcinoma

• Features must be of sarcomatoid histology
• Locally recurrent or metastatic disease not amenable to resection
• Measurable disease
• Must have a prior nephrectomy provided all other eligibility criteria are met, and adequately recovered from any recent surgery
• At least 4 weeks since prior radiotherapy and recovered
• ECOG performance status of 0-1
• WBC greater than 3,000/mm^3 or absolute neutrophil count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3
• Bilirubin less than 1.5 mg/dL
• Aspartate aminotransferase (AST) less than 2 times upper limit of normal
• Creatinine no greater than 2.0 mg/dL
• LVEF at least lower limit of normal by MUGA
• Negative pregnancy test
• Fertile patients must use effective contraception
• Other prior malignancy allowed provided patient was curatively treated and has been disease free from that cancer
• Age of 18 and over
• Diagnostic material from the kidney or metastatic site biopsy available for central pathologic review

Exclusion criteria

• Prior treatment for advanced disease
• Previously irradiated lesions as the sole site of disease for patients with prior radiation therapy
• Concurrent local radiotherapy for pain control or for life-threatening situations
• Myocardial infarction within the past year
• Congestive heart failure within the past year
• Significant ischemic or valvular heart disease within the past year
• Prior or concurrent brain metastases
• Concurrent serious medical illness that would preclude study treatment
• Active infection that would preclude study treatment
• Pregnant or nursing