Journal of Clinical Oncology, Vol 14, 1156-1164, Copyright © 1996 by American Society of Clinical Oncology
Minimal toxicity and mortality in high-risk breast cancer patients receiving high-dose cyclophosphamide, thiotepa, and carboplatin plus autologous marrow/stem-cell transplantation and comprehensive supportive care
HK Holland, SP Dix, RB Geller, SM Devine, LT Heffner, DG Connaghan, CD Hillyer, LL Hughes, RL Miller, MR Moore, EF Winton and JR Wingard
Bone Marrow Transplant Program, Emory University School of Medicine, Atlanta, GA, USA.
PURPOSE: To assess the clinical toxicity and outcome associated with a
comprehensive supportive care approach in poor-risk breast cancer (BrCA)
patients with high-dose chemotherapy (HDC). PATIENTS AND METHODS: One
hundred twenty-five consecutive patients with stages II, III or metastatic
breast cancer received HDC between February 1992 and June 1994. Recipients
received 4 days of continuous infusion of cyclophosphamide 1.5 g/m2/d,
thiotepa 125 mg/m2/d, and carboplatin 200 mg/m2/d followed by infusion of
bone marrow or peripheral-blood stem cells (PBSC) and recombinant human
growth factor (rhu-GF) support. Patients received similar supportive care
that included administration of prophylactic antibiotics, management of
neutropenic fevers, and transfusion support. RESULTS: There were 38 women
with stage II or III (27 patients with > or = 10 lymph nodes), four with
stage IIIB, and 83 with metastatic breast cancer. The median age was 44
years (range, 27 to 61). Grade II or greater nonhematologic toxicities
included diarrhea (66%), stomatitis (33%), hepatic venoocclusive disease
(VOD) (5%), and pulmonary toxicity (4%). Myeloid and platelet engraftment
was comparable between bone marrow and PBSC recipients (P > .1).
Infectious complications were rare and consisted of gram-negative
bacteremia (1.6%), gram-positive bacteremia (1.6%), fungemia (1.6%), and
documented or suspected aspergillosis infection (3%). There was one
treatment-related death secondary to severe VOD. CONCLUSION: A
comprehensive supportive care approach was associated with a low
treatment-related mortality rate of less than 1%. With the observed
reduction in treatment-related mortality, it is reasonable to evaluate the
efficacy of HDC in women with less than 10 positive nodes and stage II
disease in well-designed clinical trials.