High-dose cyclophosphamide plus carboplatin and interleukin-2 (IL-2) activated autologous stem cell transplantation followed by maintenance IL-2 therapy in metastatic breast carcinoma - a phase II study
Hc. Toh et al., High-dose cyclophosphamide plus carboplatin and interleukin-2 (IL-2) activated autologous stem cell transplantation followed by maintenance IL-2 therapy in metastatic breast carcinoma - a phase II study, BONE MAR TR, 25(1), 2000, pp. 19-24
Citations number
22
Categorie Soggetti
Hematology,"Medical Research Diagnosis & Treatment
While high-dose chemotherapy and stem cell transplantation is associated wi
th higher complete response rates than conventional chemotherapy in patient
s with metastatic breast cancer (MBC), its role in conferring a survival ad
vantage is unproven. We report the results of a prospective phase II trial
of 33 patients accrued between 1996 to 1998 with chemosensitive MBC, who re
ceived cyclophosphamide (Cy) 2000 mg/m(2)/day and carboplatin (Cb) 600 mg/m
(2)/day for 3 consecutive days, followed by infusion of peripheral blood st
em cells cultured in IL-2 for 24 h on day 0 as adoptive immunotherapy, Low-
dose interleukin-2 (IL-2) was administered from day 0 to +4 and/or +7 to +1
1, +14 to +18, +21 to +25, then 5 days per month for 11 months to augment a
graft-versus-tumor effect. The results of this study were compared to thos
e of a historical control group treated with an identical high-dose Cb + Cy
regimen with SCT but without IL-2 treatment. Only gastrointestinal (GI) to
xicity was more frequent in the IL-2 cohort (P = 0.0031). At a median follo
w-up of 18.6 months, the median progression-free survival (PFS) is 9 months
(2.4-40) and the median OS has not been reached yet. The Kaplan-Meier esti
mated 2 year PFS is 35%, compared with 17% in the control arm (P = 0.73), a
nd the estimated 2 year OS is 78%, compared with 61% in the control arm (P
= 0.22). Multivariate analysis showed that ER status was an independent pre
dictor for OS and PFS, and less chemotherapy prior to HDCSCT predicted for
a better PFS, These results show that augmenting HDC with IL-2 activated SC
T is well-tolerated. Whether a therapeutic advantage is achievable in patie
nts with MBC remains to be determined.