SAN DIEGO--A study of 1,000 patients who received high-dose chemotherapy (HDC) with peripheral blood stem cell (PBSC) support in the community setting showed treatment-related mortality rates similar to those reported at academic centers, said C. Dean Buckner, MD, scientific director of Response Oncology, Inc. and a founder of the Fred Hutchinson Cancer Research Center. He spoke at a symposium sponsored by the University of California, San Diego.
There have been numerous arguments given as to why private practice oncologists should not perform this complex procedure, including: It will increase the cost of care; transplants will be performed outside of clinical trials; transplant centers will lose patients for their own clinical trials; and private practice oncologists lack the skills to perform the procedure.
But Dr. Buckner, in his presentation at the Sixth International Symposium on Recent Advances in Hematopoietic Stem Cell Transplantation, tried to tilt the debate in favor of private oncologists. His company, Response Oncology, is a comprehensive cancer management company based in Memphis that owns and/or operates a network of outpatient treatment centers providing HDC/PBSC and other advanced cancer treatments.
The 400 medical oncologists in the Response Oncology network of 50 centers evaluate approximately 1,200 patients a year, and 650 are treated with HDC/PBSC. The company has 20 protocols and is active in 70 hospitals in 26 states.
Dr. Buckner presented a retrospective evaluation of 1,000 consecutive patients with acute myeloid leukemia (AML), non-Hodgkins lymphoma, Hodgkins disease, multiple myeloma, sarcoma, ovarian cancer, and breast cancer treated during a 5-year period (1989 to 1993) at community cancer centers in Response Oncologys network. These patients received one of five published HDC regimens followed by PBSC infusions in an outpatient setting.
Within the first 100 days after the procedure, 34 patients (3.4%) died of treatment-related mortality; 15 (1.5%) from infection; and 19 (1.9%) from regimen-related toxicities. In a logistical model, increasing age and lower numbers of CD34+ cells/kg were associated with an increased risk of treatment-related death within the first 100 days. A regimen of high-dose cyclophosphamide(Drug information on cyclophosphamide), thiotepa(Drug information on thiotepa) and carboplatin(Drug information on carboplatin) (CTCb) was associated with a lower risk of mortality than other high-dose regimens, Dr. Buckner said.
Response Oncology also examined what happened to transplant patients with several specific diseases during the first 100 days. The treatment-related mortality for relapsed malignant lymphoma patients who received carmustine(Drug information on carmustine), etoposide(Drug information on etoposide), cytarabine(Drug information on cytarabine), and cyclophosphamide (BEAC) was 3.6% to 10%.
Treatment mortality for women with newly diagnosed metastatic breast cancer who received busulfan, melphalan, and thiotepa (BuMelTT) was 7%, while there were no deaths in the same patient group among those who received CTCb. Investigators at the Fred Hutchinson Cancer Research Center have reported an 8% treatment-related mortality following BuMelTT in patients with metastatic breast cancer, which is not different than that observed in the Response Oncology network. For relapsed ovarian cancer patients receiving melphalan(Drug information on melphalan), mitoxantrone(Drug information on mitoxantrone), and carboplatin (MMC), treatment mortality was 6.9%.
"These results show that HDC and autologous PBSC support can be performed in community cancer centers with relative safety, with treatment-related mortality similar to that observed in patients treated in transplant centers," he said.
Dr. Buckner argued that practicing oncologists who treat patients with intensive chemotherapy already have the skills necessary to manage patients receiving HDC/PBSC. "Most oncologists who received their training in the past 10 years have experience with managing patients who have received allogeneic or autologous transplants," he observed. "The care of patients receiving well-tested HDC regimens with PBSC support is generally no more complex than managing patients with AML through multiple cycles of induction and consolidation."
He added that patients receiving HDC with well-established regimens have well-defined and usually manageable nonhe-matologic toxicities associated with a relatively short period of pancytopenia following the PBSC infusion.
Advantages for Patients
For patients, there are practical reasons why receiving a transplant in the community can be preferable, Dr. Buckner said. For starters, patients receiving HDC at home have better continuity of care without the social and economic costs associated with moving to an often distant transplant center for several weeks or months. The local support system of family, primary oncologist, and nurses remains intact.
Furthermore, patients are most likely to benefit from HDC if they are treated earlier in the natural history of their disease, and this is more likely to happen if treatment is available from the patients community oncologist.
For example, women with newly diagnosed advanced breast cancer who are treated with HDC/PBSC in the adjuvant setting are more likely to benefit than patients with advanced disease who have received prior chemotherapy. And outcomes with HDC are superior for patients with chemosensitive recurrent lymphoma treated with one prior regimen than for those who have received more extensive prior treatment.
This timely treatment is more likely if the community physicians endorse HDC in early disease settings and are knowledgeable with the literature and the field.
There are also some logistical reasons why community oncologists should become more involved, Dr. Buckner said. The traditional transplant referral centers will not be able to treat all the patients meeting eligibility criteria, he predicted, since HDC/PBSC appears to be emerging as the treatment of choice for newly diagnosed patients with metastatic breast cancer, multiple myeloma patients, and relapsed or refractory malignant lymphoma patients under the age of 66.
In addition, ongoing phase II and III studies may define other populations of patients for whom HDC/PBSC is a reasonable therapeutic option. Consequently, the number of potential patients likely to benefit from this procedure is large, he said. For example, it is estimated that currently only 10% to 15% of patients with non-Hodgkins lymphoma who fail initial chemotherapy receive HDC.
Most patients treated with HDC in community centers are currently not eligible for participation in NCI-sponsored trials, he said, noting that clinical trials could probably be carried out more rapidly if such patients were included.
Finally, Dr. Buckner cited certain requirements that must be met for the safe performance of HDC/PBSC in community cancer centers (see table)
Requirements for Using High-Dose Chemotherapy With Stem Cell Support in Community Cancer Centers
Treatment is delivered on protocol within the context of a clinical trial.
A data collection system is in place, and data are submitted to a central office with the capability of analyzing and reporting data from large numbers of patients.
There is a standardized and coordinated approach to supportive care and prophylaxis, and management of toxicities equal to that available in academic settings.Nurses are experienced with high-dose chemotherapy and the management of side effects.
Stem cell collection and preservation are performed under quality assurance controls.
Combined inpatient and outpatient facilities anticipate accreditation by the Foundation for the Accreditation of Hematopoietic Cell Therapy (FAHCT).
From a presentation by C. Dean Buckner, MD.