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, thiotepa and
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, etoposide, 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,
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
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
From a presentation by C. Dean Buckner, MD.