A first: Drug may safely cut mucositis symptoms
A first: Drug may safely cut mucositis symptoms
Amgen's experimental agent palifermin may become the first specific drug treatment for mucositis, a disabling side effect of high-dose chemotherapy and radiation, according to new data from a phase III study presented at a recent conference in San Diego.
The study, sponsored by Amgen, showed that patients with severe mucositis receiving palifermin (recombinant human keratinocyte growth factor, or rHuKGF) showed a 40% improvement in their ability to eat, drink, swallow, sleep, talk, and generally function. The study included 212 hematologic cancer patients with mucositis; half were given palifermin, the rest, placebo. The patients reported daily on the rawness and pain in the oral cavity caused by the ulcerations characteristic of mucositis.
"The statistically significant and clinically meaningful results of our study are especially exciting because there is no approved therapy for the treatment or prevention of this debilitating side effect," said lead investigator Patrick Stiff, M.D., director of the Cardinal Bernardin Cancer Center, Loyola University Health System, Chicago Stritch School of Medicine. He presented the new data at the annual meeting of the American Society of Hematology (ASH).
"In my practice, I typically offer lidocaine, narcotics, oral rinsesas well as Kaopectate for diarrhea for the mucositis symptoms that follow chemotherapy and radiation," said Stiff. "But at the same time I warn the patients not to expect much relief." In fact, most patients in the study rated their symptoms as a 9 or 10 on a 10-point severity scale, he noted. "About half said we did a fair-to-poor job of controlling symptoms with the usual methods." But with palifermin, the researchers found the duration and severity of mucositis was reduced by 54% compared with the placebo arm of the study.
The patients were randomized to receive either palifermin (60 mcg/kg/day) or placebo for three days prior to high-dose chemotherapy and total body irradiation. Then all patients received peripheral blood stem cell transplants followed by an additional three days of either palifermin or placebo.
Besides a lower incidence of severe mucositis, patients receiving palifermin had almost one week less pain and suffering compared with those on placebo (10.4 days versus 3.7 days). In particular, Stiff emphasized, "The new study data showed that palifermin helped protect patients from the most severe form of mucositis [grade 4]; that is, three times fewer [active drug-treated] patients developed the side effect compared with placebo-treated patients [62% versus 20%]." Additionally, he said, "Preclinical studies show that natural palifermin stimulates growth and development of epithelial cellsthose that line the gastrointestinal tract as well as the oral cavity."
Dutch investigator Nicole M.A. Blijlevens, M.D.not connected with the palifermin studysaid in a symposium on controlling infections in patients with hematologic cancers that "many clinicians don't take mucositis seriously enough, especially when it manifests in the GI tract. Yet the aerodigestive mucosa from top to bottom may be so badly damaged that only opioid analgesics can provide relief, and eating requires total parenteral nutrition." She is a specialist in hematology at the University Medical Center St. Radboud, Nimegen, Netherlands.
GI injury is more life-threatening than the pain and ulceration of oral mucositis, Blijlevens said. "Billions of microbes400 different speciesreside in the gut, aiming to penetrate the mucosal barrier.... Severe mucositis can increase the risk of serious infection, force hospitalization, and even postpone cancer treatments." Noting that no specific treatment for mucositisgut or oralexists, she listed some of the drugs currently used as palliatives both in Europe and the United States, including chlorhexidine, antibiotics, sucralfate, glutamine supplements, vitamins, and antioxidants.
"But now for the first time, perhaps there is hope for a safe and effective treatment," Blijlevens said, reviewing the upbeat palifermin results described by Stiff. "This seems to be the first experimental proof that a drug can produce a significant decline in mucositis symptoms."
The AUTHOR is a medical writer based in New York.
Naomi Pfeiffer. A first: Drug may safely cut mucositis symptoms. Drug Topics Feb. 9, 2004;148:52.
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