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

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.