Monday, March 18, 2013

Thalidomide in Metastatic Renal cell carcinoma

Renal cell carcimoma (RCC) is the third   most common genitourinary cancer after prostate and bladder. Majority (80% to 85%) of kidney tumours are malignant.  It is the most lethal malignancy of all urological cancers1
Unique characteristics of RCC
  • lack of early warning signs,
  • diverse clinical manifestations,
  • resistance to radiation and chemotherapy, and
  • immunogenic nature and spontaneous regressions.
RCC diagnosed early can be managed with nephron sparing or radical nephrectomy with excellent 5 year survival and prognosis. The problematic cases are those presenting as advanced disease at the initial presentation. The advanced disease includes: T4 N0 M0, or any T, any N, M1.  These cases are associated with poor survival and limited treatment options. This review aims to through some light on our current understanding of the pathogenic mechanisms, and the available treatment options for the management of advanced RCC.
 Pretreatment features associated with shorter survival
There are various studies identifying the pretreatment factors associated with poor survival. These are
        Low Karnofsky performance status (< 80%)
        High lactate dehydrogenase level (<; 1.5 x normal)
        Low hemoglobin level
        High serum calcium
        Absence of nephrectomy

·         Nephrectomy and resection of metastases has been   reported to prolong   the survival. Effect is enhanced with long disease-free interval between initial nephrectomy and development of metastases.
·         Survival also depends on the site of metastasis. Patients with lung metastasis only have better survival than those with other site metastasis.(Flanigan RC, et al.  N Engl J Med. 2001; 345: 1655-1659.)

    Thalidomide   is reported to suppress levels of several cytokines, angiogenic  growth factors including TNF-alpha, basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6). The resulting anti-angiogenic, immunomodulatory and growth suppressive effects form the rationale for investigating thalidomide in the treatment of malignancies. Studies have been carried out where high dose thalidomide have been administered to the patients with renal cell carcinoma (600 mg daily).Thalidomide has been given to patient s who are refractory to the immunotherapy. The partial response occurs in 9-10% patients with 30-50% patients show stable disease for a period ranging from 6 -12 months.
  We usually start patients on thalidomide if they cannot tolerate sunitinib .The side effects of sunitinib like oral ulcers sometimes cause patients to drop out from the therapy.But the toxic sideffects like neuropathy,asthenia,fatigue,constipation etc can happen.

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