Outpatient sequential high dose alkylation with stem cell support for patients with advanced breast cancer: a phase I-II study.
We evaluated the feasibility of administering, in an out-patient setting, a sequential high dose alkylating regimen with hematopoietic growth factor (HGF) and stem cell support to patients with advanced breast cancer. Peripheral blood stem cells (PBSC) were previously collected after chemotherapy and HGF. Two consecutive cycles of alkylating agents were planned: Thiotepa (T) then, 15 days later, BCNU (B). Three dose levels of each agent were administered in cohorts of consecutive patients: 400, 500 and 600 mg/m2 respectively. HGF and reinfusion of PBSC followed both cycles. Toxicity and response were evaluated according to the WHO recommendations. From April 1996 to August 1988, 30 women were enrolled: 8 in the first, 12 in the second and 10 in the third dose level. In all cases, B was administered after T with a median delay of 25 days because of grade 3/4 hematological toxicity. 4 patients did not receive B because of previous lung radiotherapy, persistent tricytopenia or insufficient PBSC collection. 19 patients with measurable lesions were considered for response. The objective response rate was 48% (11% CR, 37% PR). We recommended T and B at a dose of 600 mg/m2 to conduct a phase II study in metastatic breast cancer and even to administer B before T.
Institut Paoli-Calmettes, Marseilles, France. oncomed@marseille.fnclcc.fr
D
D
Genre
P
P
Viens
G
G
Gravis
F
F
Bertucci
D
D
Cowen
G
G
Novakovitch
S
S
Derméche
C
C
Chabannon
S
S
Oziel-Taieb
J
J
Camerlo
G
G
Houvenaeghel
J
J
Jacquemier
D
D
Maraninchi
D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000628:therapy; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D002330:Carmustine / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D003131:Combined Modality Therapy; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D000069585:Filgrastim; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins; D013852:Thiotepa / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D013852:Thiotepa; D000069585:Filgrastim; D002330:Carmustine