Toxicity of dose-dense docetaxel followed by doxorubicin with cyclophosphamide as adjuvant therapy for breast cancer in a phase II study.
OBJECTIVE
In order to evaluate the feasibility of dose-dense docetaxel followed by dose-dense AC (doxorubicin/cyclophosphamide) as adjuvant chemotherapy for operable breast cancer, we conducted a phase II study.


METHODS
In cohort 1, 28 patients received docetaxel 100 mg/m2 followed by doxorubicin 60 mg/m2 with cyclophosphamide 600 mg/m2, each every 2 weeks for 4 weeks (total of 8 cycles). Enrollment was discontinued because of stopping criteria based on significant toxicity (grade 4 hematologic toxicity or grade >or= 3 nonhematologic toxicity). In cohort 2, the docetaxel dose was reduced to 75 mg/m2; enrollment was discontinued after 18 patients.


RESULTS
Significant toxicity occurred in 79% and 72% of patients in cohorts 1 and 2, respectively, resulting in treatment delays in 50% and 17% of patients, respectively. The most common grade 4 hematologic toxicity was neutropenia, which occurred in 7% and 42% of cohort 1 patients during docetaxel and AC, respectively, and in none and 19% of cohort 2 patients, respectively. The most common grade >or= 3 nonhematologic toxicity was palmar-plantar erythrodysesthesia, which occurred in 25% and none of cohort 1 patients during docetaxel and AC, respectively. With docetaxel 75 mg/m2 and patient education encouraging routine use of topical strategies, grade 3 palmar-plantar erythrodysesthesia occurred in only 11% of cohort 2 patients. Grade 2 nail changes were also debilitating and occurred in 33% of cohort 1 patients during AC.


CONCLUSIONS
These phase II findings suggest that dose-dense docetaxel 100 mg/m2 followed by AC is not feasible and, until more studies are conducted, should be restricted to clinical studies.
Lambert-Falls
Rosemary
R
South Carolina Oncology Associates, Columbia, SC 29210, USA. rlambertfalls@sconcology.net
Modugno
Susan
S
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D003875:Drug Eruptions / Q000209:etiology; D064420:Drug-Related Side Effects and Adverse Reactions; D005240:Feasibility Studies; D005260:Female; D005533:Foot Dermatoses / Q000139:chemically induced; D006229:Hand Dermatoses / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D010292:Paresthesia / Q000139:chemically induced; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin; D003520:Cyclophosphamide