Design and development of new combinations of the CMF agents with taxanes (paclitaxel or docetaxel) in advanced breast cancer: a feasibility study.
OBJECTIVE
We previously designed and tested combinations made up of the CMF agents, two at a time by rotation, and of doxorubicin or epirubicin. The present study was aimed to similarly test new combinations made up of the CMF agents, two at a time by rotation, and paclitaxel or docetaxel.


METHODS
The doses of each taxane were escalated with the objective of reaching at least a single dose level of 90 mg/m2 of paclitaxel and 45 mg/m2 of docetaxel on days 1 and 8 of each four-week cycle. Thirty-two patients with advanced breast carcinoma were randomized to receive increasing doses of paclitaxel (45, 65, 80, 90 and 100 mg/m2) or docetaxel (30, 35, 40, 45 and 50 mg/m2) together with the CMF agents at the same dose as that used in the conventional regimen. Each dose level was administered to a triplet of patients. No direct comparison of the two taxanes was made.


RESULTS
The fourth dose level was reached for paclitaxel and docetaxel. The most important toxicities were grade 4 neutropenia and grade 1-2 nausea/vomiting and stomatitis. The objective response rate, assessed only after the third cycle at any dose level, was 31% (95% CI, 15-47%).


CONCLUSIONS
The combinations of the CMF agents (two at a time in rotation) with paclitaxel (90 mg/m2) or docetaxel (45 mg/m2) on days 1 and 8 of each four-week cycle are feasible and lead to definite signs of therapeutic activity, and the side effects are generally mild. Further studies are therefore warranted.
Cocconi
Giorgio
G
Medical Oncology Division, University Hospital, Parma, Italy. giorgio.cocconi@tin.it
Salvagni
Stefania
S
Passalacqua
Rodolfo
R
Ferrozzi
Francesco
F
Camisa
Roberta
R
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use*; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil; D008727:Methotrexate