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According to an article recently published in an early online edition of the journal Cancer, isolated limb perfusion with tumor necrosis factor and the chemotherapy agent Alkera® (melphalan) results in high treatment responses while allowing patients with soft-tissue sarcoma to undergo limb-sparing surgery.

Soft-tissue sarcomas are characterized by the growth of cancer cells in the soft tissue of the body. Soft tissues include muscles, tendons, fibrous tissue, fat, blood or lymph vessels, nerves, or the tissues around joints.

Treatment for these soft-tissue sarcomas (STS) varies; factors that influence treatment include the specific type of cancer, the place in the body where the cancer started, and the extent of the disease. Treatment may include surgery to remove the cancer if possible, chemotherapy, and/or radiation therapy. When this type of cancer develops in an extremity (arm or leg), amputation is sometimes necessary; however, this is always used as a last resort.

Isolated limb perfusion refers to a type of treatment technique in which anticancer agents are delivered into the arm or leg that contains the cancer. This allows for higher concentrations of the drug to reach the cancer before the body’s metabolic processes break down the drug. Isolated limb perfusion may be used for the treatment of STS of the extremity that has not spread to other sites in the body.

Researchers from The Netherlands recently conducted a clinical trial to further evaluate isolated limb perfusion in patients with STS of the extremity. This study included 197 patients with STS of the extremity who underwent isolated limb perfusion between 1991 and 2003.

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Patients received the chemotherapy agent melphalan and the biologic agent tumor necrosis factor (TNF). TNF stops cancer cells from replicating through several mechanisms; it stimulates different cells of the immune system to aid in killing cancer cells, and it causes damage to blood vessels that provide nutrients and oxygen to cancer cells.

Results from treatment are as follows:

  • Overall anticancer responses were achieved in 75% of patients.
  • Progressive disease occurred in only 2% of patients.
  • 71% of patients with a single site of cancer were able to have their cancer completely surgically removed; only 34% of patients with multiple sites of cancer were able to have all of their cancer completely surgically removed.
  • 13% of limbs that received isolated limb perfusion required amputation.
  • 72% of limbs could still function following treatment.
  • Side effects were easily managed.
  • At 5 years, overall survival was 53% among patients with a single site of cancer, and 39% for patients with several sites of cancer.

The researchers concluded that isolated limb perfusion with TNF and melphalan has “gained a permanent place in the multimodality treatment of locally advanced extremity STS.” Patients with locally advanced STS of the extremity should speak with their physician regarding their individual risks and benefits of all treatment options.

Reference: Grunhagen DJ, de Wilt JHW, Graveland WJ, et al. Outcome and prognostic factor analysis of 217 consecutive isolated limb perfusions with tumor necrosis factor-alfa and melphalan for limb-threatening soft tissue sarcoma. Cancer. 2006;published early online March 15, 2006.

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