Thalidomide - new treatment for cancer

Mar 8 2005

Thalidomide, famous in the 60's because of limb deformities in babies born to women who had taken it for morning sickness, was withdrawn in 1961. Now doctors say it could be used as a treatment for cancer.

The drug has been seen to slow down weight loss in patients with advanced pancreatic cancer; severe weight loss is the direct cause of death in one in five patients with advanced cancer, according to doctors from Southampton University Hospital.

Patients who took 200mg of thalidomide daily during tests did not live longer than those who did not, but their increased weight was matched by increased physical capacity.

50 patients who were terminally ill with pancreatic cancer and had lost as least 10 per cent of their body weight, took either thalidomide or a dummy drug during a 24 week trial led by Dr John Gordon. Thalidomide reduces inflammation in the body, the researchers said, although they do not know how it does. The drug is cheap and safe, if not used by pregnant patients, and has few side effects.

The authors of the report said combinations of thalidomide with nutritional supplements and pharmacological agents could lead to a better clinical outcome for pancreatic cancer patients.

Previous research has shown that thalidomide can improve the wasting typical in Aids patients and can also reduce weight loss as a result of tuberculosis. The drug reduces levels of TNF and inhibits angiogenesis, aphthous ulcers, diarrhea and Kaposi's sarcoma. Safer thalidomide analogs are under development.

Thalidomide (C₁₃H₁₀N₂O₄; phthalimido-glutarimide; one of a number of systematic names is 2-(2,6-dioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione) is a sedative and hypnotic drug. Thalidomide was synthesized at Chemie Grünenthal in West Germany in 1953.

Thalidomide is racemic - that is, it contains both left and right handed isomers in equal amounts: one enantiomer is effective against morning sickness, and the other is teratogenic. It should be noted that the enantiomers are converted to each other in vivo. That is, if a human is given D-thalidomide or L-thalidomide, both isomers can be found in the serum. Hence, administering only one enantiomer will not prevent the teratogenic effect in humans.

The drug is most toxic if taken orally and is a mild carcinogen. Other symptoms can include peripheral neuritis, numbness, paresthesias in the extremities, peripheral neuropathy, mental confusion, unsteadiness, hypotension, and absent reflexes. Excessive dosages can lead to pulmonary oedema, atelectasis or aspiration pneumonia, and refractory hypotension.

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