Autologous Bone Marrow Transplantation - Blog Science Connections

456 High-Dose Chemotherapy and ABMT in Breast Cancer
cancer patients have shown high response rates. As expected, because of the
advanced stage and chemotherapy-resistant nature of these patients' illness,
the responses have been short (13). Other investigators, who examined highdose
combination alkylating agent therapy with cisplatin as initial therapy in a
small group of premenopausal women with stage IV disease, documented an
almost 100% response rate and an approximately 50% CR rate (14). It is not yet
possible to evaluate the durability of these responses.
Our approach to therapy for nonhematologic neoplasms is to use highdose
chemotherapy early in the treatment strategy as an intensification after
three to six courses of initial standard induction chemotherapy. This approach
allows the use in overall treatment of such important drugs as doxorubicin,
drugs that cannot be escalated to any significant degree in the bone marrow
transplant program because of their significant provocation of mucositis
(15-18). With this approach, we increased the tumor response in an elderly
group of patients with small cell bronchogenic carcinoma and frequently
associated lung and heart disease. Furthermore, 6 of 32 patients treated with
this high-dose therapy were disease-free 4 years later (19).
To increase the intensity of this approach, we introduced cisplatin therapy
into the cyclophosphamide/etoposide combination, and here describe the
response and preliminary progression-free survival of 30 patients with estrogen
receptor-negative metastatic breast carcinoma and other nonhematologic
malignancies treated with this strategy. Furthermore, in the last 15 patients
studied, a randomization was performed to define more accurately the
necessity of autologous bone marrow transplantation (ABMT) for high-dose
intensification studies in patients with minimal previous chemotherapy.
MATERIALS AND METHODS
Patient Population and Supportive Care
Thirty patients received one or two courses of high-dose CVP: 4.5 g/m 2 of
cyclophosphamide, 750-900 mg/m 2
of etoposide (VP-16-213), and
120-150 mg/m 2 of cisplatin (platinum) as intensification therapy after three or
four courses of standard-dose induction (23 patients) or for relapse (7 patients).
The patients' median age was 47, with a range of 29 to 63 years. The first 15
patients registered on this study all underwent ABMT. The last 15 patients were
randomized to receive CVP with or without ABMT. All 15 patients in the
randomized study had marrow aspirated and stored, and 8 were scheduled for
ABMT. Patients who were randomized not to receive autologous bone marrow
and whose granulocytes had not recovered to 500/mm 3
by day 28 after
chemotherapy received a reinfusion of marrow. In patients scheduled for
ABMT, marrow was infused 2 or 3 days after the third and last day of high-dose
chemotherapy. The details of marrow collection, storage, and thawing were
described previously (19). Patients were prehydrated and continuously
hydrated with approximately 5 liters per day of intravenous fluids until 1 day