Supportive Care in Cancer

, Volume 28, Issue 1, pp 395–403 | Cite as

Impact of protocol change on individual factors related to course of adverse reactions to chemotherapy for breast cancer

  • Daniela Polessa PaulaEmail author
  • Vanessa I. do Brasil Costa
  • Rosane V. Jorge
  • Flávio F. Nobre
Original Article



Asthenia, myalgia, arthralgia, mucositis, abdominal pain, diarrhea, and neutropenia are adverse reactions commonly reported by women undergoing chemotherapy. Traditional approaches do not take into account the effect that chemotherapeutic changes and variable interactions can cause in adverse reactions. We aimed to identify the impact of the change of a chemotherapy protocol within the same treatment in profiles associated with adverse reactions.


A total of 166 women admitted to the Brazilian National Institute of Cancer (INCA) were followed. Polymorphisms, clinical variables, and FAC-D protocols (3 cycles of cyclophosphamide, 5-fluorouracil, and doxorubicin followed by 3 cycles of docetaxel) composed the set of independent variables analyzed. Reaction levels were recorded at the end of each chemotherapy cycle via interviews. Marginal models were fitted.


The results of marginal models for non-hematological reactions revealed that the docetaxel phase was associated with increased reaction levels compared with the FAC phase. In addition, the set of factors associated with the reactions changed in each protocol. The post-menopausal status was related to high levels of asthenia in docetaxel protocol whereas CYP2B6 polymorphism (rs3745274) was related to high levels in FAC protocol. Regarding the docetaxel phase, high levels of abdominal pain and mucositis were related to CBR3 gene (rs8133052) polymorphism and diabetes respectively.


The results suggest the need for monitoring non-hematological reactions during the docetaxel phase of FAC-D treatment. The factors related to more severe reactions depend on the chemotherapy protocol used.


Chemotherapy Adverse reactions Longitudinal models Breast cancer Polymorphisms 



The authors thank the Instituto Nacional do Cancer (INCA), the Programa de Engenharia Biomédica (Universidade Federal do Rio de Janeiro), and all of the women who participated in this study.


This work was supported by the Conselho Nacional de Pesquisa e Desenvolvimento (CNPQ) and the Fundação Carlos Chagas Filho de Amparo à Pesquisa no Rio de Janeiro (FAPERJ).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The INCA Ethics Research Committee approved the study protocol (number 129/08), and all subjects signed the informed consent form before inclusion in this study.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Programa de Engenharia Biomédica/UFRJRio de JaneiroBrazil
  2. 2.Escola Nacional de Saúde Pública – FIOCRUZRio de JaneiroBrazil
  3. 3.Instituto de Ciências Biomédicas/UFRJRio de JaneiroBrazil

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