Dose intensification of chemotherapy in advanced breast cancer: a feasibility phase II study.
OBJECTIVE
Dose intensification of chemotherapy is associated with increased response rates in advanced breast cancer. Achievement of dose incrementation is usually limited by drug-dependent bone marrow toxicity. The recent availability of recombinant human colony-stimulating factors (CSFs) have made it possible to evaluate their potential in ameliorating chemotherapy-induced myelosuppression. The aim of this study was to evaluate tolerability and effectiveness of an intensified mitoxantrone, methotrexate and mitomycin-C (3M) regimen, given with G-CSF support in patients with advanced breast cancer (ABC).


METHODS
Twenty-eight eligible patients with advanced breast cancer were treated with mitomycin -C (7 mg/sqm i.v. every 4 weeks), methotrexate (35 mg/sqm i.v.) and mitoxantrone (7 mg/sqm i.v. every 2 weeks) for 6 cycles. Recombinant human granulocyte colony-stimulating factor (r-HuG-CSF, Filgrastim) (5 micrograms/kg/day) was given subcutaneously from day 2 to day 12 after each chemotherapy administration to prevent leukopenia.


RESULTS
Of the 27 evaluable patients, 4 had complete response and 14 achieved partial response; the overall response rate was 63% (95% CI; 46.8%-82.2%). The median duration of response was 8 months (range, 4-13+). Chemotherapy-related toxicity was mild: only 3 out of 163 courses had to be postponed due to myelotoxicity.


CONCLUSIONS
The 3M regimen given at 2- week intervals is a feasible, active and well toleratel treatment in patients not previously treated for metastatic breast cancer.
Pedrazzoli
P
P
Division of Medical Oncology, Clinica del Lavoro Foundation, IRCCS, Pavia, Italy.
Zamagni
C
C
Martoni
A
A
Capotorto
A M
AM
Da Prada
G A
GA
Pavesi
L
L
Preti
P
P
Lelli
G
G
Pannuti
F
F
Robustelli della Cuna
G
G
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000517:prevention & control*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D008937:Mitomycins / Q000008:administration & dosage / Q000009:adverse effects; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome
D008937:Mitomycins; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D008942:Mitoxantrone; D000069585:Filgrastim; D008727:Methotrexate