Toxicity of dose-dense docetaxel followed by doxorubicin with cyclophosphamide as adjuvant therapy for breast cancer in a phase II study

Clin Breast Cancer. 2007 Aug;7(9):697-704. doi: 10.3816/CBC.2007.n.029.

Abstract

Purpose: 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.

Patients and 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.

Conclusion: 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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Chemotherapy, Adjuvant / adverse effects
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Docetaxel
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Drug Eruptions / etiology
  • Drug-Related Side Effects and Adverse Reactions
  • Feasibility Studies
  • Female
  • Foot Dermatoses / chemically induced
  • Hand Dermatoses / chemically induced
  • Humans
  • Middle Aged
  • Neutropenia / chemically induced
  • Paresthesia / chemically induced
  • Taxoids / administration & dosage
  • Taxoids / adverse effects

Substances

  • Taxoids
  • Docetaxel
  • Doxorubicin
  • Cyclophosphamide