Scientists from the Barbara Ann Karmanos Cancer Institute in Detroit presented data showing that by combining two treatment agents in the care of multiple myeloma patients, doctors can use higher dosages of chemotherapy before autologous stem cell transplant while alleviating painful and debilitating side effects like severe oral mucositis (mouth ulcers). The findings were announced today at the 2010 American Society of Clinical Oncology Annual Meeting.
Muneer Abidi, M.D., associate professor of Internal Medicine and Oncology and medical director of the Hematopoietic Stem Cell Lab and Apheresis and Blood and Marrow Stem Cell Collection Program at Karmanos, presented the study poster.
Dr. Abidi has led a two-part Phase I dose escalation study that enrolled patients with multiple myeloma with normal and abnormal renal function. Multiple myeloma, otherwise known as cancer of the plasma cells, can cause kidney disease, bone lesions, metabolic malfunction, elevated calcium levels that tax the kidneys, anemia and fatigue.
The drug Melphalan is the standard conditioning treatment that prepares patients for autologous stem cell transplantation. It, however, brings with it symptoms that include severe mouth ulcers at doses of 200 milligrams per meter squared or higher, precluding dose escalation.
"The intent of our study was to determine whether the use of Palifermin (a recombinant human keratinocyte growth factor) would allow us to increase the dose of Melphalan beyond the current standard," Dr. Abidi said. "When these patients have severe mucositis, they are completely disabled. There is nothing effective available in terms of prevention and pain treatment, so the only thing we have available is the use of narcotics.
"When patients develop mucositis, it affects their ability to take oral pills and it forces us to change the majority of their medications from pills to an intravenous method. It also severely limits their nutritional intake so they require intravenous nutrition supplementation. It impacts the quality of their life during hospitalization and can potentially prolong their hospital stay."
Patients who must cope with oral ulcers also run the risk of developing infections through bacteria that enters the bloodstream.
"It can have a significant impact on a patient's health and hospital course post-stem cell transplant," Dr. Abidi said.
Melphalan is administered to patients as a combating agent against cancerous plasma cells. Melphalan works to eradicate as much of the disease as possible before stem cells are infused back into the patient.
The use of Palifermin has reduced the intensity and severity of mucositis in patients. Researchers were able to increase the dosage of Melphalan up to 280 milligrams. Palifermin is an FDA-approved drug that prevents mucositis in patients that have received high-dose chemotherapy and radiation in many types of cancer.
Researchers began the study in July of 2007 and enrolled a total of 19 patients between then and September 2009. Those patients were between the ages of 18 to 74 with stage two and three multiple myeloma. All patients had normal renal function. One patient was removed due to an inability to receive all six doses of Palifermin. Of the 18 patients, eight had an overall incidence of oral mucositis at or above a grade 3 with a median duration of 10 days, with grade 4 being the most severe. Only one patient developed grade 4 mucositis with the Melphalan-Palifermin combination. Two patients out of six that were given a Melphalan dose of 280 milligrams, along with Palifermin developed no oral mucositis.
A total of 14 multiple myeloma patients with abnormal renal function have been recruited since 2007 with similar criteria to the study portion that tested Melphalan and Palifermin on patients with normal renal function. Dosage testing levels of Melphalan, however, were different considering patients with abnormal renal function exhibit more toxicity and side effects with higher levels of Melphalan. Researchers continue to recruit patients for this part of the study.
Karmanos researchers have concluded that Palifermin allows safe dose escalation of Melphalan up to 280 milligrams with acceptable toxicity levels. This result has the potential to further improve the outcomes of multiple myeloma patients undergoing an autologous stem cell transplant.
"The study has been very successful," Dr. Abidi said. "With the dose that we have used, we have successfully demonstrated that an increased dose of 280 milligrams is very promising."
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