A feasibility study evaluating docetaxel-based sequential and combination regimens in the adjuvant therapy of node-positive breast cancer

• Published in: Annals of oncology Vol. 11; no. 2; pp. 169 - 175
• Main Authors: Di Leo, A., Crown, J., Nogaret, J.-M., Duffy, K., Bartholomeus, S., Dolci, S., Rowan, S., O'Higgins, N., Paesmans, M., Larsimont, D., Riva, A., Piccart, M. J.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.02.2000
• Subjects: adjuvant therapy; Adult; Aged; Antineoplastic agents; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biological and medical sciences; breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Breast Neoplasms - surgery; Chemotherapy; Chemotherapy, Adjuvant; Confidence Intervals; Cyclophosphamide - administration & dosage; Docetaxel; Dose-Response Relationship, Drug; Doxorubicin - administration & dosage; Drug Administration Schedule; feasibility; Feasibility Studies; Female; Female genital diseases; Fluorouracil - administration & dosage; Follow-Up Studies; Gynecology. Andrology. Obstetrics; Humans; Lymphatic Metastasis; Medical sciences; Methotrexate - administration & dosage; Middle Aged; Neoplasm Staging; Paclitaxel - administration & dosage; Paclitaxel - analogs & derivatives; Pharmacology. Drug treatments; Survival Rate; Taxoids; Treatment Outcome; Tumors; Antineoplastic agent; Human; Drug combination; Toxicity; Treatment efficiency; Docetaxel; Adjuvant treatment; Controlled therapeutic trial; Administration schedule; Lymphatic nodule; Malignant tumor; Multiple dose; Mammary gland diseases; Chemotherapy; Taxane derivatives; Feasibility; Mammary gland
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1023/A:1008345432342

Background and purpose: Docetaxel is an active agent in the treatment of metastatic breast cancer. We evaluated the feasibility of docetaxel-based sequential and combination regimens as adjuvant therapies for patients with node-positive breast cancer. Patients and methods: Three consecutive groups of patients with node-positive breast cancer or locally-advanced disease, aged ≤ 70 years, received one of the following regimens: a) sequential A → T → CMF: doxorubicin 75 mg/m2 q 3 weeks × 3, followed by docetaxel 100 mg/m2 q 3 weeks × 3, followed by i.v. CMF days 1 + 8 q 4 weeks × 3; b) sequential accelerated A → T -→ CMF: A and T were administered at the same doses q 2 weeks; c) combination therapy: doxorubicin 50 mg/m2 + docetaxel 75 mg/m2 q 3 weeks × 4, followed by CMF × 4. When indicated, radiotherapy was administered during or after CMF, and tamoxifen started after the end of CMF. Results: Seventy-nine patients have been treated. Median age was 48 years. A 30% rate of early treatment discontinuation was observed in patients receiving the sequential accelerated therapy (23% during A → T), due principally to severe skin toxicity. Median relative dose-intensity was 100% in the three treatment arms. The incidence of G3-G4 major toxicities by treated patients, was as follows: skin toxicity a: 5%; b: 27%; c: 0%; stomatitis a: 20%; b: 20%; c: 3%. The incidence of neutropenic fever was a: 30%; b: 13%; c: 48%. After a median follow-up of 18 months, no late toxicity has been reported. Conclusions: The accelerated sequential A → T → CMF treatment is not feasible due to an excess of skin toxicity. The sequential non accelerated and the combination regimens are feasible and under evaluation in a phase III trial of adjuvant therapy.