Seeking the Causes of Oral Lesions in Patients on Chemotherapy

SAN DIEGO--Despite acknowledged oral complications associated with chemotherapy agents, there is nothing in the literature pointing to the causes.

This prompted Monique Vincent, RN, BN, a senior research nurse at M.D. Anderson Cancer Center, and her colleagues to initiate a study to look at the incidence of oral lesions in patients receiving liposomal doxorubicin (Doxil) and make the differentiation between localized oral problems and those throughout the oral cavity.

Ms. Vincent presented the study at the 26th Annual Conference of the Oncology Nursing Society (abstract 107).

Oral ulceration is a major cause of dose modification and treatment delays in patients receiving liposomal doxorubicin, she said. The ulcerative lesions are painful, restrict oral intake, and, as portals of entry for indigenous oral microbiotic flora, can potentially lead to sepsis.

The lesions, stomatitis and mucositis, are inflammations of the oral mucous membrane. Although stomatitis is site specific and characterized by local reactions, mucositis, Ms. Vincent said, is generalized and induced by chemotherapy.

"You see them mostly in the mouth, but they can go into the gastrointestinal tract," she said. "This is an issue for most of the anthracycline-containing chemotherapy regimens and for high-dose therapy all across the board."

With use of liposomal doxorubicin, she said, about 30% of patients have mouth problems, "but there’s nothing in the literature that points to the exact cause. Is it chemical deposits in the skin? Is it superimposed infections? We don’t know and are looking to find that out."

Ms. Vincent’s team has received funding for enrollment of 20 patients, a number she acknowledged is a suboptimal sample size. She is hoping, however, that if she can provide the patients with dental care, follow them closely, and get interesting results, she can convince the sponsor, Alza Pharmaceuticals, to provide further funding for additional patients.

The trial duration is four courses of chemotherapy for each patient or removal from liposomal doxorubicin chemotherapy. "The reason we decided on four visits is that, generally, if people are going to have complications, they appear early on," she said.

Eligible patients are those beginning single-agent liposomal doxorubicin therapy. They will be referred to dental oncology at the initiation of therapy, and their overall oral health will be assessed, with incidental oral and dental pathologies corrected.

Participants will also be given a dental cleaning and instruction in oral care. Patients will keep a daily log recording oral care habits and symptoms. If symptoms develop, they will return to see dental oncology for care.

The differential diagnosis of stomatitis vs mucositis will be made using the Mucositis Grading Score and the Oral Toxicity Score, with samples collected for culture and treatment initiated as necessary. Based on the recommendations of dental and medical oncology, additional therapy will be initiated.

Researchers will use descriptive statistics to report demographic data, occurrence, predisposing factors, and etiology, with the results used to direct further studies aimed at treatment and preventative strategies.

The study commenced in February 2001, but Ms. Vincent noted that they have run into problems at M.D. Anderson because the institution does not have an adequate population of liposomal doxorubicin-naïve patients.

"When they come to us, they’ve generally failed that therapy and need to be started on different agents," she said. "So, we’re having a hard time finding those 20 people. We’ve screened 11 patients during the first 2 months of the trial, and none were eligible."

Of those 11 patients, three were screened for the trial after receiving the first dose of liposomal doxorubicin, three wanted to go into the trial but were getting treatment outside of M.D. Anderson, two patients chose alternative therapies, one chose combination therapy, one had a performance status that was too low, and one refused consent.

So, the larger challenge right now is recruitment, which Ms. Vincent is trying to accomplish by informing and educating the clinic staff, speaking to scheduling clerks and the people who process orders, and posting bulletins on the pharmacy computer system that force the pharmacist to call her before dispensing any liposomal doxorubicin.

This strategy has yet to yield any candidates, so the researchers will also be seeking a collaboration with a community gynecologic oncology practice where they know liposomal doxorubicin is frequently used.

"We would bring patients in to see our dental oncologists for screenings," Ms. Vincent said. "If there are problems, we would bring them back for treatment with no out-of-pocket expenses for the patients."