HIGH-DOSE CISPLATIN, ETOPOSIDE, AND CYCLOPHOSPHAMIDE WITH AUTOLOGOUS STEM-CELL REINFUSION IN PATIENTS WITH RESPONSIVE METASTATIC OR HIGH-RISK PRIMARY BREAST-CANCER
G. Somlo et al., HIGH-DOSE CISPLATIN, ETOPOSIDE, AND CYCLOPHOSPHAMIDE WITH AUTOLOGOUS STEM-CELL REINFUSION IN PATIENTS WITH RESPONSIVE METASTATIC OR HIGH-RISK PRIMARY BREAST-CANCER, Cancer, 73(1), 1994, pp. 125-134
Background. This study was designed to establish the feasibility of co
mbining high-dose cisplatin, etoposide, and cyclophosphamide followed
by stem cell rescue in patients with responsive metastatic or high-ris
k primary breast cancer.Methods. Eligibility criteria included the pre
sence of high-risk primary breast cancer (Stage II with 10 or more inv
olved axillary nodes or Stage IIIA or B) or Stage IV disease in comple
te or partial response; physiologic age 50 years or younger; Karnofsky
performance status of 80% or greater; and creatinine clearance of 80
ml/minute or greater. Chemotherapy consisted of escalating doses of ci
splatin (50-150 mg/m(2) intravenously [IV]) given on days -12 and -5,
etoposide (30 mg/kg IV) given on days -12 and -5, and cyclophosphamide
(100 mg/kg IV) on day -3. On day 0, autologous bone marrow with or wi
thout peripheral stem cells, or granulocyte colony-stimulating factor
primed peripheral stem cells alone were reinfused. Results. Thirty pat
ients were enrolled in this study. Twenty-eight patients demonstrated
no evidence of persistent renal damage after treatment. Two patients s
uffered symptomatic peripheral neuropathy, and one patient required a
hearing aid 3 months after therapy. Hematopoietic toxicities were acce
ptable. There were two fatalities; Streptococcus viridans bacteremia a
nd adult respiratory distress syndrome developed in one patient; and o
ne patient who received 262 mg/m(2) of cisplatin died of renal failure
. Twelve of 18 assessable patients with Stage IV disease are without e
vidence of progression; 3 of these patients are progression-free at 11
+, 12+, and 32+ months. With a median follow-up of 16+ months (range,
4-31 months), 7 patients of the group of 11 treated with high-risk pri
mary breast cancer are without evidence of disease. Conclusions. The P
hase II dose of cisplatin when given on a day -12 and day -5 schedule
in combination with etoposide and cyclophosphamide has been establishe
d at a total of 250 mg/m(2). Dose-limiting toxicity has been defined a
s renal failure, and response rates were comparable to previously repo
rted high-dose chemotherapeutic regimens.