Leukocyte nadir as a predictive factor for efficacy of adjuvant chemotherapy in breast cancer. Results from the prospective trial SBG 2000-1.

Abstract

Background: Retrospective studies have suggested that chemotherapy-induced leukopenia is associated with improved recurrence-free or overall survival. The SBG 2000-1 trial was designed to verify the favorable prognosis associated with chemotherapy-induced leukopenia in early breast cancer. Patients not experiencing chemotherapy-induced leukopenia were randomized into standard dosed or individually escalated chemotherapy doses based on the grade of leukopenia after a first standard dose.Patients and methods: 1452 women in Sweden and Denmark with operable node-positive or high-risk node-negative breast cancer aged 18-60 years were recruited to participate in this trial. Participants received a first FEC cycle at standard doses (600/60/600 mg/m2). Patients (n = 1052) with nadir leukopenia grade 0-2 after the first cycle were randomized between either 6 standard FEC or 6 tailored FEC courses with doses of epirubicin and cyclophosphamide escalated during courses 2 and 3 and thereafter aimed at achieving grade 3 leukopenia. Patients with nadir leukopenia grade 3-4 after the first course continued treatment with standard FEC. Results of the randomized comparison has been published previously. The present study focuses on chemotherapy-induced leukopenia as a covariable with outcome in randomized and non-randomized patients. The prognostic value of leukopenia after course 3, was studied in a Cox model adjusted for cumulative doses of epirubicin and cyclophosphamide. The association of chemotherapy-induced leukopenia with prognosis was a preplanned secondary endpoint for this trial.Results: The eight-year distant disease-free survival was 73%, 77%, 78% and 83% for patients with leucocyte nadir grade 0, 1, 2 and 3-4, respectively. Higher degree of leukopenia was highly significantly associated to improved distant disease-free survival (HR 0.84, 95% CI 0.74-0.96, p = .008) and overall survival (HR 0.87 (0.76-0.99, p = .032).Conclusion: This prospective study confirms that chemotherapy-induced leukopenia is a covariable with outcome in primary breast cancer, even after adjustment for chemotherapy doses.

• Authors: Paula Poikonen-Saksela, Henrik Lindman, Asgerdur Sverrisdottir, Per Edlund, Kenneth Villman, Lena Tennvall Nittby, Søren Cold, Troels Bechmann, Lars Stenbygaard, Bent Ejlertsen, Michael Andersson, Carl Blomqvist, Jonas Bergh, Johan Ahlgren
• Journal: Acta oncologica (Stockholm, Sweden) (Acta Oncol) Vol. 59 Issue 7 Pg. 825-832 (Jul 2020) ISSN: 1651-226X [Electronic] England
• PMID: 32347139 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Epirubicin
• Cyclophosphamide
• Fluorouracil

Topics

• Adolescent
• Adult
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Breast Neoplasms (drug therapy, surgery)
• Chemotherapy, Adjuvant
• Cyclophosphamide (administration & dosage, adverse effects)
• Disease-Free Survival
• Epirubicin (administration & dosage, adverse effects)
• Female
• Fluorouracil (administration & dosage, adverse effects)
• Humans
• Leukocyte Count
• Leukopenia (blood, chemically induced)
• Middle Aged
• Prospective Studies
• Survival Rate
• Treatment Outcome
• Young Adult