title: 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.
abstract: 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.
authors.affiliation: Bone Marrow Transplant Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: H C
authors.initials: HC
authors.lastname: Toh
authors.forename: S L
authors.initials: SL
authors.lastname: McAfee
authors.forename: R
authors.initials: R
authors.lastname: Sackstein
authors.forename: P
authors.initials: P
authors.lastname: Multani
authors.forename: B F
authors.initials: BF
authors.lastname: Cox
authors.forename: R
authors.initials: R
authors.lastname: Garcia-Carbonero
authors.forename: C
authors.initials: C
authors.lastname: Colby
authors.forename: T R
authors.initials: TR
authors.lastname: Spitzer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016019:Survival Analysis; D014182:Transplantation, Autologous
chemical_list: D007376:Interleukin-2; D003520:Cyclophosphamide; D016190:Carboplatin