Toxicity Assessment of a Phase III Study Evaluating FEC-Doc and FEC-Doc Combined with Gemcitabine as an Adjuvant Treatment for High-Risk Early Breast Cancer: the SUCCESS-A Trial

Abstract

Introduction: This paper aims to evaluate the toxicity profile of additive gemcitabine to adjuvant taxane-based chemotherapy in breast cancer patients. Methods: Patients enrolled in this open-label randomized controlled Phase III study were treated with 3 cycles of epirubicin-fluorouracil-cyclophosphamide (FEC) chemotherapy followed by 3 cycles of docetaxel with those receiving 3 cycles of FEC followed by 3 cycles of gemcitabine-docetaxel (FEC-DG). 3690 patients were evaluated according to National Cancer Institute (NCI) toxicity criteria (CTCAE). The study medications were assessed by the occurrence of grade 3–4 adverse events, dose reductions, postponements of treatment cycles and granulocyte colony-stimulating factor (G-CSF) support. Results: No differences in neutropenia or febrile neutropenia were demonstrated. However, thrombocytopenia was significantly increased with FEC-DG treatment (2.0 vs. 0.5 %, p < 0.001), as was leukopenia (64.1 vs. 58.5 %, p < 0.001). With FEC-DG significantly more G-CSF support in cycles 4 to 6 (FEC-DG: 57.8 %, FEC-D: 36.3 %, p < 0.001) was provided. Transaminase elevation was significantly more common with FEC-DG (SGPT: 6.3 %, SGOT: 2 %), whereas neuropathy (1.2 %), arthralgia (1.6 %) and bone pain (2.6 %) were more common using FEC-D. Dose reductions > 20 % (4 vs. 2.4 %) and postponement of treatment cycles (0.9 vs. 0.4 %) were significantly more frequent in the FEC-DG arm. Eight deaths occurred during treatment in the FEC-DG arm and four in the FEC-D arm. Conclusion: The addition of gemcitabine increased hematological toxicity and was associated with more dose reductions and postponements of treatment cycles.

Zusammenfassung

Einleitung: Die vorliegende Studie untersucht das Toxizitätsprofil nach der zusätzlichen Gabe von Gemcitabin in Kombination mit einer adjuvanten Taxan-basierten Chemotherapie bei Patientinnen mit Brustkrebs. Methode: Es handelt sich hier um eine randomisierte kontrollierte Phase-III-Open-Label-Studie. Alle in der Studie aufgenommenen Patientinnen erhielten 3 Zyklen Epirubicin-Fluorouracil-Cyclophosphamid (FEC) gefolgt von 3 Zyklen Docetaxel bzw. 3 Zyklen FEC gefolgt von 3 Zyklen Gemcitabin-Docetaxel (FEC-DG). Die Daten von insgesamt 3690 Patientinnen wurden mittels der Toxizitätskriterien (CTCAE) des nationalen Krebsinstituts der USA (National Cancer Institute [NCI]) ausgewertet. Kriterien für die Auswertung der Studienmedikation waren das Auftreten unerwünschter Ereignisse 3. oder 4. Grades, Dosisreduktionen, Verschiebungen nachfolgender Behandlungszyklen und Granulozytenkolonie-stimulierender Faktor (G-CSF)-Gabe. Ergebnisse: Es zeigten sich keine Unterschiede zwischen den beiden Gruppen hinsichtlich der Entwicklung einer Neutropenie oder einer febrilen Neutropenie. Dagegen war die Thrombozytopenie nach der Behandlung mit FEC-DG signifikant erhöht (2,0 vs. 0,5 %, p < 0,001), und die Leukopenie trat in dieser Gruppe ebenfalls deutlich häufiger auf (64,1 vs. 58,5 %, p < 0,001). Der Einsatz von G-CSF-Präparaten in den Zyklen 4–6 war deutlich höher in der FEC-DG-Gruppe (FEC-DG: 57,8 %, FEC-D: 36,3 %, p < 0,001). Ein Transaminasenanstieg kam wesentlich häufiger in der FEC-DG-Gruppe vor (SGPT: 6,3 %, SGOT: 2 %), während Neuropathien (1,2 %), Arthralgien (1,6 %) und Knochenschmerzen (2,6 %) häufiger in der FEC-D-Gruppe auftraten. Dosisreduktionen > 20 % (4 vs. 2.4 %) sowie eine Verschiebung nachfolgender Behandlungszyklen (0,9 vs. 0,4 %) kamen deutlich häufiger im FEC-DG-Studienarm vor. Während der Behandlung starben 8 Patientinnen im FEC-DG-Studienarm und 4 im FEC-D-Studienarm. Schlussfolgerung: Die zusätzliche Gabe von Gemcitabin hat die hämatologische Toxizität erhöht und war mit mehr Dosisreduktionen und mehr Verschiebungen nachfolgender Behandlungszyklen assoziiert.

Key words

adjuvant chemotherapy - gemcitabine - toxicity - hematological - breast cancer

Schlüsselwörter

adjuvante Chemotherapie - Gemcitabin - Toxizität - hämatologisch - Brustkrebs

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