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Title
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High-dose cyclophosphamide + 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
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HC Toh1,2, SL McAfee1, R Sackstein1, P Multani1, BF Cox1, R Garcia-Carbonero2, C Colby1 & TR Spitzer1
1Bone Marrow Transplant Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
2Division of Hematology-Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Correspondence to: Dr TR Spitzer, Bone Marrow Transplant Program, Massachusetts General Hospital, Cox 640, 100 Blossom Street, Boston, MA 02114, USA
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Abstract
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While high-dose chemotherapy and stem cell transplantation is associated with higher complete response rates than conventional chemotherapy in patients with metastatic breast cancer (MBC), its role in conferring a survival advantage is unproven. We report the results of a prospective phase II trial of 33 patients accrued between 1996 to 1998 with chemosensitive MBC, who received cyclophosphamide (Cy) 2000 mg/m2/day and carboplatin (Cb) 600 mg/m2/day for 3 consecutive days, followed by infusion of peripheral blood stem 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 +11, +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 those of a historical control group treated with an identical high-dose Cb + Cy regimen with SCT but without IL-2 treatment. Only gastrointestinal (GI) toxicity was more frequent in the IL-2 cohort (P = 0.0031). At a median follow-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 estimated 2 year PFS is 35%, compared with 17% in the control arm (P = 0.73), and 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 predictor 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 SCT is well-tolerated. Whether a therapeutic advantage is achievable in patients with MBC remains to be determined. Bone Marrow Transplantation (2000) 25, 19–24.
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Keywords |
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high dose chemotherapy and stem cell transplantation; metastatic breast cancer; interleukin-2; graft-versus-tumor effect; adoptive immunotherapy
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Received 13 May 1999; Accepted 2 August 1999

©
Macmillan Publishers Ltd 2000
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