DURHAM, N.C. - Researchers at Duke University Medical Center have identified a lung condition that if not treated promptly can limit therapy choices for women undergoing high-dose chemotherapy and bone marrow transplantation (BMT) for breast cancer.
The Duke team followed 45 women and found side effects to the lungs that were different and less severe than any reported previously in the medical literature. The disorder, termed delayed pulmonary toxicity syndrome (DPTS) by the Duke researchers, can be successfully treated by inexpensive corticosteroids (prednisone) if diagnosed early in the course of a woman's cancer treatment.
About 64 percent of the women in the Duke study demonstrated symptoms of DPTS, with no reported mortality, and those treated with steroids saw 17 percent improvement in pulmonary function.
The results of the Duke study, led by pulmonologist Rodney Folz, were published Thursday (Feb. 19) in the February issue of the American Journal of Respiratory and Critical Care Medicine. The research was supported by two National Institutes of Health grants.
High-dose chemotherapy coupled with BMT is becoming an increasingly important way of treating breast cancer. Chemotherapy kills dividing cells, particularly cancer cells and immune system cells. To avoid killing immune cells, physicians remove the bone marrow that produces them before beginning treatment.
After the course of chemotherapy is completed, the bone marrow cells are re-infused into the patient (autologous transplant), where they grow and create a new immune system. In some cases, women receive bone marrow from donors (allogeneic transplant).
"We have long known that the higher the dose of chemotherapy, the better the cancer kill rate is," Folz said. "In patients receiving this treatment for breast cancer, what limits our ability to increase the doses of chemotherapy are the negative side effects to the lungs and other tissues."
The researchers believe that the chemotherapeutic agents cause subtle injuries to the lung tissue, and as the patient's immune system recovers after the bone marrow transplant, increasing numbers of immune cells migrate to the site of injury, causing inflammation.
"The onset of DPTS is usually five to 15 weeks after the cancer treatment, a time when many patients are recovering from the chemotherapy and transplant and are starting to feel better," Folz said. "All of a sudden, they develop cold-like symptoms -- a cough and shortness of breath.
"If you can detect this inflammation early and modify the body's inflammatory response through steroids, you may prevent or significantly minimize the lung toxicity," Folz said. "Lung toxicity is one of the major limiting factors in choosing options for future therapy for these women."
For example, many women who receive chemotherapy and BMT also receive radiation treatment as soon as six weeks later, Folz said. However, radiation is often delayed or canceled in women with lung damage.
"Since breast tissue and the lungs lie along the same plane, the radiation beams aimed at the tumor also hit the lungs, causing further damage," Folz said.
Physicians have known about another toxicity to lungs from high-dose chemotherapy and BMT, called idiopathic pulmonary syndrome (IPS), which occurs much sooner in cancer treatment, is more severe, and does not respond to steroid treatment.
The main difference between the Duke patients and previous studies describing IPS is the source of the immune cells re-infused into patients. All the Duke patients received autologous transplants, while the patients in published IPS studies received allogeneic transplants.
There are other differences between the Duke patients and previous studies describing IPS. In addition to receiving autologous transplants, the Duke patients were treated using the same chemotherapy protocol and were followed very closely for signs and symptoms of lung toxicity. Patients in published IPS studies received mostly allogeneic transplants and received a wide variety of chemotherapy protocols with variable follow-up.
Folz said that age, baseline pulmonary functions and smoking history were not predictive of which patients would develop DPTS.
Joining Folz in the research were Dr. Stephen Wilcznski, Dr. Jeremy Erasmus, Dr. William Petros and Dr. James Vredenburgh, all from Duke.