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.
Medical Oncology Division, University Hospital, Parma, Italy. giorgio.cocconi@tin.it
Giorgio
G
Cocconi
Stefania
S
Salvagni
Rodolfo
R
Passalacqua
Francesco
F
Ferrozzi
Roberta
R
Camisa
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