Chimioterapia neoadjuvantă cu Docetaxel, Epirubicină şi Ciclofosfamidă în cancerul de sân

 Neoadjuvant chemotherapy with Docetaxel, Epirubicin and Cyclophosfamide in breast cancer

First published: 25 aprilie 2017

Editorial Group: MEDICHUB MEDIA

Abstract

Purpose. To establish the efficacy of neoadjuvant (NA) Docetaxel (DOC) with anthracycline-based therapy and to determine the toxicity of NA DOC associated with Epirubicin and Cyclophoasfamide in patients with breast cancer.
Patients and methods. Patients with breast cancer treated between January 2013 and December 2013 were taken into account for this study. There were included into the study 48 patients with breast cancer locally advanced, stages IIB, IIIA, IIIB, IIIC, treated in the Department of Medical Oncology I - IOB. None of the patients included were male. There were administered 6 cycles of TEC (Docetaxel 75 mg/m2 day 1, Epirubicin 75 mg/m2 day 1, Cyclophosphamide 500 mg/m2 day 1 at 21 days). Clinical tumor response was assessed at cycle 4. After 6 cycles patients who became operable went through surgical intervention. There were included patients regardless of immunohistochemistry tets - taking into accont that Trastuzumab was not reimbursed for neoadjuvant setting at that time.
Results. 48 patients were enrolled. All patients completed 6 cycles of TEC treatment. At 6 series, 33 patients had surgical interventions. The remaining 15 patients in the study group were as follows: 4 patients - stable disease, 6 patients - partial remission (RECIST> 30%) but have not converted to operability, 4 patients - progressive disease (even after 4 series only one patient had progressive disease), 3 of the patients with stationary disease have had subsequent progression, 1 patient refused surgical intervention. GM-CSF were administered prophylactic; it was done the prophylaxis of mucositis. Adverse reactions more commonly observed were: hematologic toxicity (neutropeniae, anemiae, and trombocitopeniae), hepatic toxicity, digestive toxicity - more frequent of grade 1 or 2, less frequent of grade 3-4. After 24 months, 25 from 48 patients developed local recurrence or distant metastases.
Conclusion. Neoadjuvant therapy type TEC (Docetaxel, Epirubicin, Ciclofosfamid) resulted in substantial improvement in responses to DOC. TEC is a series of chemotherapy relatively well tolerated with RR superior to other neoadjuvant chemotherapy regimes - according to literature, in locally advanced breast cancer cases, such as the study by Kuerer HM, Newman Smith TL et al. “Clinical course of breast cancer patients with pathologic complete axillary lymph node primary tumor and response to doxorubicin based neoadjuvant chemotherapy”, J Clin Oncol 1999; 17; 460-469, which showed a pathologic complete response at 20% of the ganglionic cases. Patients with Her 2 positive disease received adjuvant Trastuzumab; neoadjuvant administration of Trastuzumab was not reimbursed, HR positive disease received adjuvant hormonal treatments. Adjuvant radiotherapy was administered to patients according to international guidelines.

Keywords
breast cancer, neoadjuvant treatment, prospective study

Rezumat

Scopul studiului. Stabilirea eficacităţii şi toxicităţii terapiei neodjuvante cu Docetaxel, Epirubicin şi Ciclofosfamidă administrată pacientelor cu cancerele mamare biopsiate.
Pacienţi şi metodă: Au fost incluse în analiză paciente cu cancer mamar tratate în cadrul Institutului Oncologic Bucureşti în perioada ianuarie 2013 - decembrie 2013. Au fost analizate cazurile a 48 de paciente cu cancer mamar în stadiile IIB, IIIA, IIIB, IIIC tratate în Departamentul de Oncologie Medicală I. Nu a fost inclus nici un pacient de sex masculin. Au fost administrate 6 cicluri de tip TEC (Docetaxel 75 mg/m2 ziua 1, Epirubicin 75mg/m2 ziua 1, Ciclofosfamidă 500 mg/m2 ziua 1 la 21 de zile). Răspunsul tumoral a fost evaluat clinic la ciclul 4. După 6 cicluri de chimioterapie de tip TEC, pacientele care au devenit operabile au suferit intervenţie chirurgicală. Au fost incluse paciente, indiferent de rezultatul testelor imunohistochimice - ţinând cont de faptul că Trastuzumabul nu era rambursat pentru terapie neoadjuvantă în acel moment.
Rezultate. 48 de paciente au fost înrolate. Toate pacientele au finalizat 6 cicluri de tratament TEC administrat neoadjuvant (după biopsie şi evaluare imagistică iniţială pentru excluderea metastazelor). După 6 serii, 33 de paciente au suferit intervenţii chirurgicale. Restul de 15 paciente din grupul de studiu au prezentat: boală stabilă 4 paciente, 6 paciente - remisiune parţială (RECIST>30%), dar nu s-au convertit la operabilitate, 4 paciente - boala progresivă, chiar şi după 4 serii doar un pacient a avut boală progresivă, 3 dintre pacientele cu boală staţionară au avut progresii ulterioare, o pacientă - a refuzat intervenţia chirurgicală. GM-CSF au fost administrate profilactic, s-a efectuat profilaxia mucozitei. Reacţiile adverse mai frecvente observate au fost: toxicităţi hematologice (neutropenie, anemie, trombocitopenie), toxicitate hepatică, toxicitate digestivă - mai multe de gradul 1 sau 2, mai puţine de grad 3-4. După 24 de luni, 25 din 48 de paciente au prezentat recurenţă locală sau metastaze la distanţă.
Concluzie. Terapia neoadjuvantă de tip TEC a dus la o îmbunătăţire substanţială a răspunsurilor la DOC. TEC este o serie de chimioterapie relativ bine tolerată, cu RR superioară altor regimuri de chimioterapie neoadjuvantă - aşa cum reiese din literatura de specialitate, în cazul pacientelor cu cancer mamar avansat, cum ar fi studiul de la MD Anderson Cancer Center FAC neoadjuvant: Kuerer HM Newman Smith TL şi colab. “Clinical course of breast cancer patients with pathologic complete axillary lymph node primary tumor and response to doxorubicin based neoadjuvant chemotherapy”. Pacientele cu boală Her2 pozitivă au primit adjuvant trastuzumab; administrarea neo-adjuvantă a trastuzumabului  nu a fost rambursată, pacientele cu boală HR pozitivă au primit tratamente hormonale adjuvante. Radioterapia adjuvantă a fost administrată pacientelor în conformitate cu ghidurile internaţionale.

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