High-dose alkylating agents with autologous hematopoietic stem cell support and trastuzumab in ERBB2 overexpressing metastatic breast cancer: a feasibility study.
BACKGROUND
ERBB2 overexpression predicts a worse outcome for patients receiving high-dose chemotherapy (HDC). Trastuzumab improves response rate and survival in ERBB2 overexpressing metastatic breast cancer patients (MBC). We investigated the feasibility of combining high-dose alkylating agents with autologous hematopoietic stem cell (AHSC) support and trastuzumab in ERBB2 overexpressing MBC.


METHODS
Eleven consecutive patients with pre-treated ERBB2 overexpressing MBC were enrolled. HDC regimen consisted of a single course of cyclophosphamide 120 mg/kg + melphalan 140 mg/m2 (CyMEL, n =8), a single course of Thiotepa 600 mg/m2 (TTP, n = 1) or a sequential combination of Thiotepa 600 mg/m2 followed on day 21 by BCNU 600 mg/m2 (TTP-BCNU, n =2). Trastuzumab (4mg/kg) was started 24 h after AHSC infusion and then administered weekly (2 mg/kg).


RESULTS
Median time to neutrophil and platelet recovery was 10 and 14.5 days, respectively. Three patients experienced febrile neutropenia and in 2 Herpes virus infections were documented. Five grade III/IV mucositis/oesophagitis were recorded. One patient experienced a reversible atrial arrhythmia on day 2 of trastuzumab, and another patients had a nonsymptomatic decrease in LVEF >10% on week 12 of trastuzumab. No toxic death was recorded. Median time to progression was 5 months (1 to 38 +).


CONCLUSIONS
Combining alkylating agent-based HDC and trastuzumab appears to be feasible in ERBB2 overexpressing MBC and warrants further investigation in a larger cohort.
Gonçalves
A
A
Department of Medical Oncology, Institut Paoli-Calmettes, 13273 Marseille Cedex 9, France. goncalvesa@marseille.fnclcc.fr
Braud
A C
AC
Viret
F
F
Tarpin
C
C
Charaffe-Jauffret
E
E
Jacquemier
J
J
Maraninchi
D
D
Viens
P
P
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001792:Blood Platelets / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000628:therapy*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D005240:Feasibility Studies; D005260:Female; D006321:Heart / Q000187:drug effects; D006801:Humans; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009504:Neutrophils / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D012306:Risk; D033581:Stem Cell Transplantation; D013997:Time Factors; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; D008558:Melphalan; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab