July 08, 2011 . By Helen Albert . Contaminated cocaine use can cause painful, necrotic skin purpura . By Springer . MedWire News: Using cocaine contaminated with the animal de-worming drug levamisole can result in painful, necrotic purple skin lesions and low levels of white blood cells, report US researchers.
"We've seen a lot of cases in Rochester alone, so it is important to alert the gatekeepers of medicine, the primary care physicians who are in the trenches every day, of this diagnosis," said study author Mary Gail Mercurio from the University of Rochester in New York.
"This is one of those entities that with familiarity and recognition, can go a long way in helping physicians to quickly make a diagnosis and intervene without embarking on an elaborate workup where nothing will pan out," she said.
Co-author Noah Craft (University of California, Los Angeles) and colleagues describe a series of six patients with remarkably similar dermatological symptoms after cocaine use, treated in clinics in New York and California over the past few months.
Symptoms included net-like purple skin discoloration or purpura on the body, which included painful eruptions, skin necrosis, and scabbing, all occurring after cocaine use.
In addition, all the patients had positive perinuclear antineutrophil cytoplasmic antibody values, a common feature of many autoimmune conditions. Three also had a low white blood cell count (neutropenia), which can significantly increase infection risk.
The study authors believe that the cause of these symptoms is contamination of the cocaine with levamisole, rather than cocaine use per se, as the symptoms of purpura and neutropenia have been observed before in connection with levamisole-contaminated cocaine use.
Craft et al explain that levamisole-contaminated cocaine has been in use in the USA since 2003, and resulting toxic reactions have increased dramatically since 2008.
"When we first started seeing these patients they all had a similar clinical picture, but they were really an enigma because they weren't falling into any other pattern we'd seen before. When a colleague at the National Institutes of Health mentioned levamisole contamination, we did toxicity screens and lo-and-behold, all the patients came up positive for cocaine," said Mercurio.
She concluded: "We believe these cases of skin reactions and illnesses linked to contaminated cocaine are just the tip of the iceberg in a looming public health problem posed by levamisole."
The results of this study are published in the Journal of the American Academy of Dermatology.
For people with metastatic pancreatic cancer, the chemotherapy combination known as FOLFIRINOX results in better overall survival than standard treatment with Gemzar® (gemcitabine), but also increases side effects. These results were published in the New England Journal of Medicine.
Pancreatic cancer is one of the deadliest forms of cancer. Each year, approximately 43,000 people are diagnosed with pancreatic cancer in the United States and close to 37,000 die from the disease. The disease is often diagnosed at an advanced stage, and treatment of advanced disease remains challenging.
Gemzar has been a standard chemotherapy drug for the treatment of advanced pancreatic cancer for some time. Recent results, however, suggest that the combination known as FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) may be more effective.
To compare FOLFIRINOX with Gemzar, researchers in France conducted a Phase II-III clinical trial among 342 patients with metastatic pancreatic cancer. Study participants had not previously been treated with chemotherapy. All had a good performance status, meaning that they were generally able to carry out activities of daily living.
Overall survival among was 11.1 months among patients in the FOLFIRINOX group and 6.8 months among patients in the Gemzar group.
Progression-free survival was also significantly improved among the FOLFIRINOX group: 6.4 months versus 3.3 months.
Severe side effects that were more common in the FOLFIRINOX group included low white blood cell counts (sometimes accompanied by fever), low platelet counts, diarrhea, and sensory neuropathy (a nerve problem that causes pain, numbness, tingling, swelling, or muscle weakness).
The researchers conclude that compared with Gemzar, FOLFIRINOX improves survival but also increases side effects. They note “FOLFIRINOX is an option for the treatment of patients with metastatic pancreatic cancer and good performance status.”
Reference: Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. New England Journal of Medicine. 2001;364:1817-25. news.cancerconnect.com
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In two separate Phase III clinical trials, the targeted drugs Sutent® (sunitinib) and Afinitor® (everolimus) delayed the progression of advanced pancreatic neuroendocrine tumors. These results were published in the New England Journal of Medicine.
Pancreatic neuroendocrine tumors are a relatively uncommon type of cancer that develops in the hormone-producing cells of the pancreas.
Sutent is an oral targeted agent that works by inhibiting multiple biologic pathways involved in the growth, replication, and spread of cancer cells. It has been shown to be effective in the treatment of selected patients with kidney cancer or gastrointestinal stromal tumors, and is also being evaluated in the treatment of other types of cancer.
To evaluate Sutent for the treatment of advanced pancreatic neuroendocrine tumors, researchers conducted a Phase III clinical trial among 171 patients who had experienced cancer progression. Half the patients were treated with Sutent, and half were treated with a placebo.
Progression-free survival was 11.4 months among patients treated with Sutent and 5.5 months among patients treated with placebo.
Patients treated with Sutent also experienced better overall survival than patients treated with placebo.
The most common serious side effect of Sutent was neutropenia (a low white blood cell count), which affected 12% of patients.
A second clinical trial evaluated Afinitor for the treatment of advanced pancreatic neuroendocrine tumors. Afinitor is an oral targeted therapy that works by inhibiting a protein known as the mammalian target of rapamycin (mTOR). The mTOR protein plays an important role in regulating cancer cell division and blood vessel growth. Afinitor is used in the treatment of selected patients with kidney cancer or subependymal giant cell astrocytoma (SEGA), and is also being evaluated for the treatment of other types of cancer.
The study of Afinitor enrolled 410 patients with advanced, low-grade or intermediate-grade pancreatic neuroendocrine tumors. Half the patients were treated with Afinitor and half were treated with a placebo.
Progression-free survival was 11 months among patients treated with Afinitor and 4.6 months among patients treated with placebo.
34% of patients treated with Afinitor were alive and free of cancer progression at 18 months, compared with 9% of patients treated with placebo.
Serious side effects of Afinitor included anemia and high blood sugar.
The results of these studies suggest that Sutent and Afinitor may improve outcomes among patients with advanced pancreatic neuroendocrine tumors.
References:
Raymond E, Dahan L, Raoul J-L et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. New England Journal of Medicine. 2011;364:501-513.
Yao JC, Shah MH, Ito T et al. Everolimus for advanced pancreatic neuroendocrine tumors. New England Journal of Medicine. 2011;364:514-523. news.cancerconnect.com
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