ORIGINAL ARTICLE
Evaluation of the Clinical Profile of Patients with Gynecological Tumors undergoing Antineoplastic Treatment
Avaliação do Perfil Clínico de Pacientes com Tumores Ginecológicos em Tratamento Antineoplásico
Evaluación del Perfil Clinico de Pacientes con Tumores Ginecológicos Sometidos a Tratamiento Antineoplásico
doi: https://doi.org/10.32635/2176-9745.RBC.2022v68n1.1879
Ana Paula do Nascimento Antonio1; Thiago Ribeiro Nery2; Liliana Rosa Alves Manaças3; Priscila Helena Marietto Figueira4
1,3,4National Cancer Institute José Alencar Gomes da Silva (INCA). Cancer Hospital II (HCII). Rio de Janeiro (RJ), Brazil. E-mails: nascimento.apna@gmail.com; lmanacas@inca.gov.br; pfigueira@inca.gov.br. Orcid iD: https://orcid.org/0000-0003-0049-8868; Orcid iD: https://orcid.org/0000-0002-7832-3745; Orcid iD: https://orcid.org/0000-0002-6918-0391
2Fundação Getulio Vargas (FGV). Rio de Janeiro (RJ), Brazil. E-mail: t.rnery@hotmail.com. Orcid iD: https://orcid.org/0000-0002-1228-2864
Corresponding author: Ana Paula do Nascimento Antonio, Via Binário do Porto, 831 ‒ Santo Cristo. Rio de Janeiro (RJ), Brazil. CEP 20081-250. E-mail: nascimento.apna@gmail.com
ABSTRACT
Introduction: The evaluation of the causes of interruption of the antineoplastic therapeutic plan allows the development of strategies that increase adherence and positive treatment outcomes. Objective: Outline the clinical profile of the patients with gynecological tumors under intravenous antineoplastic treatment, identifying the risk of interrupting the therapeutic plan. Method: Retrospective and quantitative study (2011-2018), including patients older than 18 years old, with gynecological tumors undergoing antineoplastic treatment. The database was built from the spreadsheets of antineoplastic drug handling at the Chemotherapy Center. The variables collected were: year of treatment, age, type of tumor, purpose of treatment, protocol, medication, dose, start and end of treatment, and treatment interruption. Results: 6,496 patients over 8 years were evaluated. Fifty two percent of the patients presented cervical cancer. Almost forty eight percent (47.6%) showed a palliative treatment purpose for their tumors. Approximately, twenty three percent (22.6%) interrupted the antineoplastic treatment. For adjuvant, curative, and palliative purposes the age range 18-30 presented the highest interruption, respectively 33%, 36% and 41%. The paclitaxel/carboplatin protocol was the most prescribed with a significant percentage of interruption. Conclusions: The findings suggest that there is an association between treatment discontinuation and patients' age and therapeutic purpose.
Key words: genital neoplasms, female; drug-related side effects and adverse reactions; antineoplastic agents; withholding treatment.
RESUMO
Introdução: A avaliação das causas de interrupção do plano terapêutico antineoplásico permite a elaboração de estratégias que aumentem a adesão e os desfechos positivos do tratamento. Objetivo: Traçar o perfil clínico das pacientes com tumores ginecológicos, em tratamento antineoplásico intravenoso, identificando o risco de interrupção do plano terapêutico. Método: Estudo retrospectivo e quantitativo (2011-2018), incluindo pacientes maiores de 18 anos, com tumores ginecológicos em tratamento antineoplásico. O banco de dados foi construído a partir das planilhas de controle de antineoplásicos da Central de Quimioterapia. As variáveis coletadas foram ano de tratamento, idade, tipo de tumor, finalidade do tratamento, protocolo, medicamento, dose, início e término do tratamento e interrupção do tratamento. Resultados: Avaliaram-se 6.496 pacientes ao longo de oito anos. Cinquenta e dois por cento das pacientes apresentavam câncer cervical. Quase 48% (47,6%) apresentaram uma finalidade de tratamento paliativo para seus tumores. Aproximadamente 23% (22,6%) interromperam o tratamento antineoplásico. Para fins adjuvantes, curativos e paliativos, a faixa etária de 18 a 30 anos apresentou a maior interrupção, respectivamente 33%, 36% e 41%. O protocolo paclitaxel/carboplatina foi o mais prescrito com percentual significativo de interrupção. Conclusão: Os achados sugerem que exista uma associação entre a suspensão do tratamento e a idade dos pacientes e a finalidade terapêutica.
Palavras-chave: neoplasias dos genitais femininos; efeitos colaterais e reações adversas relacionados a medicamentos; antineoplásicos; suspensão de tratamento.
RESUMEN
Introducción: La evaluación de las causas de interrupción del plan terapéutico antineoplásico permite el desarrollo de estrategias que aumentan la adherencia y los resultados positivos del tratamiento. Objetivo: Delinear el perfil clínico de las pacientes con tumores ginecológicos, en tratamiento antineoplásico intravenoso, identificando el riesgo de interrupción del plan terapéutico. Método: Estudio retrospectivo y cuantitativo (2011-2018), que incluyó a pacientes mayores de 18 años, con tumores ginecológicos en tratamiento antineoplásico. La base de datos se construyó a partir de las hojas de cálculo del manejo de fármacos antineoplásicos en el Centro de Quimioterapia. Las variables recogidas fueron: año de tratamiento, edad, tipo de tumor, finalidad del tratamiento, protocolo, medicación, dosis, inicio y finalización del tratamiento e interrupción del mismo. Resultados: Se evaluaron 6.496 pacientes durante los ocho años. El 52% de las pacientes presentó cáncer de cuello uterino. Casi el 48% (47,6%) mostró un propósito de tratamiento paliativo para sus tumores. Aproximadamente, el 23% (22,6%) interrumpió el tratamiento antineoplásico. Para fines adyuvantes, curativos y paliativos, el rango de edad de 18 a 30 años presentó la mayor interrupción, respectivamente 33%, 36% y 41%. El paclitaxel/carboplatino fue el más prescrito con un porcentaje significativo de interrupción. Conclusiones: Nuestros hallazgos sugieren que existe una asociación entre la interrupción del tratamiento y la edad de los pacientes y el propósito terapéutico.
Palabras clave: neoplasias de los genitales femeninos; efectos colaterales y reacciones adversas relacionados con medicamentos; antineoplásico; privación de tratamiento.
INTRODUCTION
According to Siegel et al.1, cancer is the second cause of death and the major public health issue in the world. Gynecological cancers are among the 10 cancers that most affect women worldwide with considerable mortality2,3. In relation to their types, it has been mainly affecting cervix, ovary, endometrium (body of the uterus), vulva and vagina, but it can also occur in embryonic attachments, like placenta, as gestational trophoblastic neoplasia4-8.
Gynecological tumors have different histological subtypes requiring distinct treatment and management modalities, commonly surgery and chemotherapy. Chemotherapy may precede surgery (neoadjuvant), administered after surgery (adjuvant) or palliative. Radiotherapy and brachytherapy are also typically used in combination with the antineoplastics treatment5-8. All treatment strategies have certain degree of risk and could be harmful to the patient. Antineoplastic drugs have been used in chemotherapy treatment and, due to its toxicity, may cause adverse drug reactions (ADRs) in different degrees, occurring during drug infusion and later9.
Antineoplastic treatment can present toxicities, which can cause its temporary or permanent interruption, requiring a reassessment of the therapeutic plan. Cytopenia, such as neutropenia and thrombocytopenia, is an important cause for treatment interruption, especially febrile neutropenia10-12. Other factors that may affect the continuity of the antineoplastic treatment are decline of patient performance status, advanced age, prolonged hospitalizations and extensive disease11,12.
By calculating the interruption rate of antineoplastic treatment protocols, it is possible to identify profiles with greater susceptibility to discontinuation, and to propose strategies for better adequacy of the therapeutic plans.
There are some studies in literature addressing treatment interruption rates as seen in Won et al.13 (54.6%), Woopen et al.14 (38.5%), Wildes et al.15 (26.2%), Aaldriks et al.16 (28.5%), Kalsi et al.17 (15.7%) and Extermann et al.18 (50.9%). However, they differ from each other due to the number of patients and tumor types. These studies involved other than gynecological tumors.
In the scope of gynecological tumors, no findings relating clinical data of these tumors in the Brazilian population with the susceptibility to interrupt therapeutic plans were found, demonstrating the relevance of the findings of the current study.
This study aimed to outline the clinical profile of the patients with gynecological tumors receiving intravenous antineoplastic treatment and identify the risk of interrupting the therapeutic plan.
Study Design
Retrospective and quantitative study conducted from 2011 to 2018 at the Chemotherapy Center of the Cancer Hospital II of the National Cancer Institute José Alencar Gomes da Silva, a treatment unit of the public health system specialized in gynecological cancer.
Patient selection and data collection
The study included patients older than 18 years with gynecological tumors undergoing antineoplastic treatment from 2011 to 2018. Patients enrolled in clinical research protocols were excluded, since the interruption of the treatment is assessed according to the specific protocol.
The database was built from the data entered at spreadsheets of antineoplastic drug handling at the Chemotherapy Center. The variables analyzed were: year of treatment, patient age, type of tumor, purpose of treatment (curative, neoadjuvant, adjuvant and palliative), protocol, medication and dose.
The analysis of treatment interruption was based on the number of protocol cycles prescribed and treatment visit dates.
In order to determine the absolute and relative frequencies of tumor types, gynecological tumors of the Endometrium (Uterus, Endometrium and Body of the Uterus), Gestational Trophoblastic (placenta, hydatidiform mole and choriocarcinoma), Cervical (Cervical, Vagina and Vulva) and Ovarian were considered.
The Institutional Review Board of INCA approved the study, number 3.451.467, which collected and utilized data from the Pharmacy Service routine.
Statistical analysis
Descriptive statistics was performed for the variables: age, type of tumor, treatment purpose, protocol, and treatment conclusion. The influence of these variables on treatment interruption was tested using the chi square test, which evaluates the dependence between categorical variables.
With SPSS and Microsoft Excel, it was possible to analyze the antineoplastic infusion dates, identifying the treatment interruption. Statistical analyses were completed using IBM SPSS 22.0 (IBM Co., Ar-monk, NY, USA) and p<0.05 was considered significant.
6,496 patients over 8 years were evaluated, with mean of 815 (920-736) per year. The clinical and therapeutic characteristics of these patients are summarized in Table 1.
Fifty two percent of the patients had cervical tumors, and 29.4%, ovarian cancer. 97.8% were treated on an outpatient basis, and 2.2% on an inpatient basis. 47.6% of the cases were palliative treatment. Furthermore, 22.6% of the patients interrupted the antineoplastic treatment.
This study described that gynecological tumors affect middle-aged older women (51-70 years old) mainly, with an incidence of 49.6% (3,221 women). However, the incidence in the youngest women was also high 38.1% (2,472 women, 18-50 years old).
Table 2 shows the treatment interruption by purpose and age range, presenting a different reality other than the hypothesis adopted. For adjuvant, curative and palliative purposes, the age range of 18-30 years had the highest interruption rate, 33%, 36% and 41%, respectively. For neoadjuvant purpose, the age range with highest interruption was 51-70, with 21%. Apart from curative purposes, the association between age, treatment purpose and interruption was significant.
|
Table 2. Association between treatment interruption by treatment purpose and age range. p<0.05 was considered significant |
|||||||
|
Interruption by age and treatment purpose (n=6,496) |
|||||||
|
Treatment purpose |
Age range |
Treatment interrupted |
Treatment completed |
Total |
p value |
||
|
n |
% |
n |
% |
||||
|
Adjuvant |
18-30 |
15 |
33% |
29 |
67% |
44 |
0.011 |
|
31-50 |
41 |
16% |
214 |
84% |
255 |
|
|
|
51-70 |
102 |
15% |
578 |
85% |
679 |
|
|
|
70+ |
28 |
17% |
139 |
83% |
168 |
|
|
|
Curative |
18-30 |
31 |
36% |
56 |
64% |
87 |
0.26 |
|
31-50 |
40 |
29% |
99 |
71% |
140 |
|
|
|
51-70 |
16 |
21% |
59 |
79% |
75 |
|
|
|
70+ |
2 |
29% |
5 |
71% |
7 |
|
|
|
Neoadjuvant |
18-30 |
17 |
14% |
103 |
86% |
120 |
0.007 |
|
31-50 |
136 |
15% |
767 |
85% |
903 |
|
|
|
51-70 |
163 |
21% |
627 |
79% |
790 |
|
|
|
70+ |
17 |
13% |
116 |
87% |
134 |
|
|
|
Palliative |
18-30 |
37 |
41% |
53 |
59% |
53 |
0.041 |
|
31-50 |
241 |
29% |
592 |
71% |
592 |
|
|
|
51-70 |
463 |
27% |
1,224 |
73% |
1,224 |
|
|
|
70+ |
133 |
27% |
352 |
73% |
352 |
|
|
Table 3 presents the association between treatment interruption by purpose and tumor type. This association was significant for cervical, endometrial and ovarian tumors. For cervical cancer, palliative and adjuvant purposes had the highest interruption rates, respectively 31% and 29%. Endometrial tumors presented rates of 27% for neoadjuvant and palliative purposes. Ovarian tumors showed the highest rates for curative purpose (45%). For gestational trophoblastic neoplasia, the highest rates were curative and palliative purposes, respectively, 31% and 75%, however, it presents statistical bias due to the low incidence of the palliative purpose.
The main reasons for discontinuing treatment, in order of incidence, were: toxicity, disease progression, worsening performance status, referral to the exclusive palliative care unit, lack of adherence to treatment and death during treatment. During this period, 18.2% (1,179) patients died.
The main protocols recommended for cervical tumors treatment were paclitaxel-combined carboplatin (CARBOTAX) and radiotherapy-combined cisplatin (CDDP+RT). These protocols present, respectively, 29% and 18% of interruption rate, as shown in Table 4. CARBOTAX was a palliative protocol and CDDP+RT was a curative protocol.
CARBOTAX and Doxorubicin monotherapy were the main protocols for endometrial tumors, with respectively, 16% and 38% of interruption.
Ovarian tumors also feature CARBOTAX as one of the major protocols, along with gemcitabine alone. For these protocols, the percentage of interruption was, respectively, 10% and 31%.
The main protocol for gestational trophoblastic neoplasia was methotrexate intramuscularly (MTX IM), with 19% of interruption rate.
|
Table 4. Association between treatment interruption by protocol* and tumor type. p<0.05 was considered significant |
|||||||
|
Protocol by interruption and cancer site (n=6,390) |
|||||||
|
Cancer site |
Protocol |
Treatment interrupted |
Treatment concluded |
Total |
p value |
||
|
n |
% |
n |
% |
||||
|
Cervical |
ADM |
8 |
57% |
6 |
43% |
14 |
0.0 |
|
CARBO monotherapy |
15 |
65% |
8 |
35% |
23 |
|
|
|
CARBOTAX |
358 |
29% |
868 |
71% |
1,226 |
|
|
|
CDDP+RT |
367 |
18% |
1,656 |
82% |
2,023 |
|
|
|
EC |
7 |
54% |
6 |
46% |
13 |
|
|
|
TAX |
15 |
65% |
8 |
35% |
23 |
|
|
|
TOPO weekly |
18 |
95% |
1 |
5% |
19 |
|
|
|
Endometrium (body of uterus) |
ADM |
34 |
38% |
55 |
62% |
89 |
0.0 |
|
ADM+CDDP |
2 |
25% |
6 |
75% |
8 |
|
|
|
CARBO monotherapy |
17 |
49% |
18 |
51% |
35 |
|
|
|
CARBOTAX |
142 |
16% |
724 |
84% |
866 |
|
|
|
CDDP+RT |
5 |
23% |
17 |
77% |
22 |
|
|
|
IFO monotherapy |
6 |
86% |
1 |
14% |
7 |
|
|
|
TAX |
7 |
47% |
8 |
53% |
15 |
|
|
|
TOPO weekly |
2 |
40 |
3 |
60% |
5 |
|
|
|
Ovarian |
BEP |
37 |
54% |
32 |
46% |
69 |
0.0 |
|
CARBO monotherapy |
43 |
40% |
65 |
60% |
108 |
|
|
|
CARBOTAX |
111 |
10% |
1,042 |
90% |
1,153 |
|
|
|
GEMCITABINE |
92 |
31% |
203 |
69% |
295 |
|
|
|
GEMCITABINE+CARBO |
5 |
16% |
26 |
84% |
31 |
|
|
|
TAX |
51 |
39% |
79 |
61% |
130 |
|
|
|
TOPO weekly |
43 |
47% |
48 |
53% |
91 |
|
|
|
Gestational trophoblastic |
ACTD |
16 |
100% |
1 |
0% |
17 |
0.0 |
|
EMA-CO |
2 |
12% |
15 |
88% |
17 |
|
|
|
MTX IM |
13 |
19% |
54 |
81% |
67 |
|
|
|
TETP |
8 |
53% |
7 |
47% |
15 |
|
|
|
Captions: *ACTD = Actinomycin; ADM = Doxorubicin; CDDP = Cisplatin; BEP = Blemycin+Etoposide+Cisplatin; CARBO= Carboplatin monotherapy; CARBOTAX= Carboplatin+Paclitaxel; EC = Etoposide+Carboplatin; EMA-CO = Etoposide+Methotrexate+Actinomycin+Cyclophosphamide+Vincristine; IFO = Iphosphamide; IM = Intramuscular; MTX = Methotrexate; RT = Radiotherapy; TAX = Paclitaxel; TETP = Cisplatin+Etoposide+Paclitaxel; TOPO = Topotecan. |
|||||||
Considering the toxicity of antineoplastic treatment as the most frequent cause of interruption, and the widespread use of the protocols CARBOTAX and CDDP+RT, in 2018, 4 carboplatin and 1 cisplatin related adverse reactions were reported.
The dose adjustment of the antineoplastic in relation to the previous cycle was present in most interrupted treatments (62%), and in those that were not interrupted (58%), this result was statistically significant.
|
Table 5. Association between treatment interruption by dose adjustment. p<0.05 was considered significant |
|||||
|
Treatment interruption by dose adjustment (n=48,876) |
|||||
|
Dose adjustment |
Treatment interrupted |
Treatment concluded |
p value |
||
|
n |
% |
n |
% |
||
|
Without dose adjustment |
2,294 |
38% |
17,784 |
42% |
0.0 |
|
With dose adjustment |
3,805 |
62% |
24,993 |
58% |
|
|
Total |
6,099 |
100% |
42,777 |
100% |
|
DISCUSSION
Although older adults present higher risk of toxicity due to reduced bone marrow reserve and renal and hepatic clearance capacity19, young and middle-aged adults are also at risk. The socioeconomic situation and the presence of a support network20 are crucial for the completion of the chemotherapy treatment in all age groups. Another perspective to be evaluated is the access to antineoplastic treatment21, especially for persons with poor financial status, which may have influenced the high number of patients in palliative chemotherapy. The difficulty of access, on the other hand, makes people seek oncologic services at a very advanced stage of the disease.
In Table 1, most patients were treated with palliative purpose, almost 50% (47.6%) as observed. We could observe that palliative purpose is targeted to patients with metastatic tumors. The table shows a worrying reality of Brazilian patients, where many of them had metastases, limiting the use of curative therapeutic protocols.
Globally, cervical cancer is the most prevalent gynecological tumor, however the incidence and mortality rates show a decreasing tendency, greatly influenced by vaccination, screening and early diagnosis policies, especially in developed countries2. In this logic, a small portion of women have metastatic tumors of the cervix, requiring palliative treatment in developed countries, probably justifying the shorter survival of these patients due to the absence of standard palliative treatment22,23.
The second most common type of gynecological tumor, ovarian cancer, does not portray the same reality2. Regardless of the population's socioeconomic level, screening methods and early diagnosis are scarce, which explains the diagnosis in advanced stages and the high lethality of this type of tumor24. Approximately 70% of the patients with ovarian cancer are diagnosed in advanced stage, requiring palliative treatment through different therapeutic lines23,24.
The data presented by Renna Junior and Azevedo e Silva20, from 2000 to 2012 in Brazil, shows that most of the women with cervical cancer were diagnosed at stages III and IV (advanced disease with metastasis), corresponding to palliative antineoplastic treatments.
Renna Junior and Azevedo e Silva20, like Carvalho et al.21 in their respective studies, present a significant percentage of patients in advanced stage at the time of diagnosis with definition of the therapeutic plan, which is an aggravating factor, since it limits the possibilities of cure. This is the Brazilian reality about cervical cancer, quite different from what is seen in most parts of the world.
Treatment interruption for tumor types such as cervical, ovarian, and endometrial have been evaluated in some studies such as Li et al.25 with 40% and Krusun et al.26 with 18.7% of interruption for cervical cancer. Data from Jang et al.27 demonstrate that for most patients with ovarian and cervical tumors, palliative chemotherapy was discontinued early, with an average of 3 cycles performed. Woopen et al.14 found around 38%, Muralikrishnan et al.28, 19.2%, Chambers et al.29, 28.1%, and Falandry et al.30, 26.1% for ovarian cancer. Khouri et al.31 detected 20% of interruption for endometrial cancer and de Boer et al.32, around 20%.
Most patients with gynecological cancers are older adults, as shown in Table 2 and data about risk of antineoplastic treatment is found in the literature for this population. This risk is increased due to the greater vulnerability of normal tissues to chemotherapy, resulting in a higher incidence of toxicities that may promote treatment interruption24. Therefore, it is possible to notice association between age and treatment interruption for neoadjuvant, adjuvant and palliative purposes. Krusun et al.26, Woopen et al.14, Won et al.13, Wildes et al.15 and Kalsi et al.17 have not found any association between age and treatment interruption, unlike Hurria et al.33.
Contrary to the literature, Table 2 shows a high percentage of interruption of antineoplastic treatment in the age range 18-30 years for adjuvant, curative, and palliative purposes. These interruption rates are not expected, since age-related functional decline is not present23.
A very high range of antineoplastic protocols was not addressed in the scope of the article. While some were used for a few patients and with high rates of interruption, others like CARBOTAX were widely used, with rates not so high, but requiring special attention, mainly due to the risk of toxicity.
De Boer et al.32 presents the interruption of carboplatin + paclitaxel /cisplatin protocols associated with radiotherapy increased as more cycles were applied, reflecting accumulation of toxicity.
An alternative to treatment interruption due to associated toxicity is dose adjustment/reduction. Won et al.13, Kalsi et al.17 and Aaldriks et al.16 utilized the evaluation of patients who have taken the full dose and the reduced dose in their studies. 62% (n=33,783) of the interrupted treatments had dose adjustment, indicating that, possibly, these patients had some degree of toxicity in previous cycle, or even alteration of the body surface due to weight gain or loss, and in renal function.
The data corroborate the information from Renna Junior and Azevedo e Silva20 and Carvalho et al.21 about public policies gaps for screening and early detection of cervical cancer; therefore, it is possible to infer that it is necessary to rethink the therapeutic plans not only for this tumor, but for gynecological tumors in general, in order to reduce early treatment discontinuation, mainly for young and middle-aged patients. However, it is also necessary to think about strategies for early detection and screening of endometrium and ovary tumors, which, although not easily preventable and traceable like cervix tumor, may have their risk factors modified and detected prior to reaching more advanced stages.
The study has limitations due to its retrospective nature as information bias and the events that occurred in the past. Another difficulty was the access to computerized information because of the long period investigated, unavailability of data of the early years, and evaluation of the outcome of different therapeutic approaches due to sub-notification.
CONCLUSION
The findings suggest that there is an association among treatment discontinuation and tumor type, patients' age and therapeutic purpose, whereas metastatic tumors, middle-aged and older patients in palliative chemotherapy are more likely to discontinue treatment.
Further studies will be needed to identify the factors that contribute to the discontinuity of the proposed treatments as those patient-related, toxicity of antineoplastic agents and/or definition of the therapeutic plan.
A more accurate analysis of treatment interruption by tumor type, age range and treatment line, assessing change between treatment lines, is among the future perspectives, looking for interruption reasons, especially when they are related to toxicity, in order to correlate to the active search for pharmacovigilance realized in our unit.
CONTRIBUTIONS
Priscila Helena Marietto Figueira, Liliana Rosa Alves Manaças, and Ana Paula do Nascimento Antonio designed the study. Ana Paula do Nascimento Antonio collected and analyzed the data and drafted the manuscript. Thiago Ribeiro Nery and Ana Paula do Nascimento Antonio conducted the statistical analyzes. Liliana Rosa Alves Manaças. and Priscila Helena Marietto Figueira supported the data interpretation and Ana Paula do Nascimento Antonio, Liliana Rosa Alves Manaças and Priscila Helena Marietto Figueira supported the drafting of the manuscript.
ACKNOWLEDGEMENTS
To residents, pharmacists, and pharmacy technicians of the Pharmacy Service of Cancer Hospital II.
CONFLICTS OF INTEREST
There is no conflict of interest to declare.
FUNDING
None, except for residency.
REFERENCES
1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7-34. doi: https://doi.org/10.3322/caac.21551
2. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. doi: https://doi.org/10.3322/caac.21492
3. Instituto Nacional de Câncer José Alencar Gomes da Silva. Estimativa 2020: incidência de câncer no Brasil. Rio de Janeiro: INCA; 2019.
4. Pimenta JM, Maluf FC, Calabrich A, et al. Cérvice. In: Buzaid AC, Maluf FC, Lima CMR. organizadores. Manual de oncologia clínica do Brasil. São Paulo: Dendrix; 2015. p. 342-59.
5. National Comprehensive Cancer Network. Plymouth Meeting, PA: NCCN; c2021. NCCN Guidelines: uterine neoplasms; Version: 1.2019.
6. National Comprehensive Cancer Network. Plymouth Meeting, PA: NCCN; c2021. NCCN Guidelines: cervical cancer. Version: 3.2019.
7. National Comprehensive Cancer Network. Plymouth Meeting, PA: NCCN; c2021. NCCN Guidelines: vulvar cancer. Version: 2.2019.
8. National Comprehensive Cancer Network. Plymouth Meeting, PA: NCCN; c2021. NCCN Guidelines: ovarian cancer. Version: 2.2018.
9. Bertolazzi LG, Lanza MVC, Bitencourt EC, et al. Incidência e caracterização de reações adversas imediatas à infusão de quimioterápicos em hospital sentinela. Arq Ciênc Saúde. 2015;22(3):84. doi: https://doi.org/10.17696/2318-3691.22.3.2015.107
10. Laskey RA, Poniewierski MS, Lopez MA, et al. Predictors of severe and febrile neutropenia during primary chemotherapy for ovarian cancer. Gynecol Oncol. 2012;125(3):625-30. doi: https://doi.org/10.1016/j.ygyno.2012.03.015
11. Taha A, Vinograd I, Sakhnini A, et al. The association between infections and chemotherapy interruptions among cancer patients: prospective cohort study. J Infect. 2015;70(3):223-9. doi: https://doi.org/10.1016/j.jinf.2014.10.008
12. Adjogatse D, Thanopoulou E, Okines A, et al. Febrile neutropaenia and chemotherapy discontinuation in women aged 70 years or older receiving adjuvant chemotherapy for early breast cancer. Clin Oncol (R Coll Radiol). 2014;26(11):692-6. doi: https://doi.org/10.1016/j.clon.2014.05.002
13. Won HS, Sun DS, Choi JY, et al. Factors associated with treatment interruption in elderly patients with cancer. Korean J Intern Med. 2019;34(1):156-64. doi: https://doi.org/10.3904/kjim.2016.318
14. Woopen H, Richter R, Ismaeel F, et al. The influence of polypharmacy on grade III/IV toxicity, prior discontinuation of chemotherapy and overall survival in ovarian cancer. Gynecol Oncol. 2016;140(3):554-8. doi: https://doi.org/10.1016/j.ygyno.2016.01.012
15. Wildes TM, Ruwe AP, Fournier C, et al. Geriatric assessment is associated with completion of chemotherapy, toxicity, and survival in older adults with cancer. J Geriatr Oncol. 2013;4(3):227-34. doi: https://doi.org/10.1016/j.jgo.2013.02.002
16. Aaldriks AA, Maartense E, Nortier HJWR, et al. Prognostic factors for the feasibility of chemotherapy and the Geriatric Prognostic Index (GPI) as risk profile for mortality before chemotherapy in the elderly. Acta Oncol. 2016;55(1):15-23. doi: https://doi.org/10.3109/0284186X.2015.1068446
17. Kalsi T, Babic-Illman G, Fields P, et al. The impact of low-grade toxicity in older people with cancer undergoing chemotherapy. Br J Cancer. 2014;111(12):2224-8. doi: https://doi.org/10.1038/bjc.2014.496
18. Extermann M, Boler I, Reich RR, et al. Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score. Cancer. 2012;118(13):3377-86. doi: https://doi.org/10.1002/cncr.26646
19. Cortez AJ, Tudrej P, Kujawa KA, et al. Advances in ovarian cancer therapy. Cancer Chemother Pharmacol. 2018;81(1):17-38. doi: https://doi.org/10.1007/s00280-017-3501-8
20. Renna Junior NL, Azevedo e Silva G. Tendências temporais e fatores associados ao diagnóstico em estágio avançado de câncer do colo uterino: análise dos dados dos registros hospitalares de câncer no Brasil, 2000-2012. Epidemiol Serv Saúde. 2018;27(2):e2017285. doi: https://doi.org/10.5123/S1679-49742018000200003
21. Carvalho PG, O´Dwer G, Rodrigues NCP. Trajetórias assistenciais de mulheres entre diagnóstico e início de tratamento do câncer de colo uterino. Saúde Debate. 2018;42(118):687-701. doi: https://doi.org/10.1590/0103-1104201811812
22. Feliu J, Heredia-Soto V, Gironés R, et al. Can we avoid the toxicity of chemotherapy in elderly cancer patients? Crit Rev Oncol Hematol. 2018;131:16-23. doi: https://doi.org/10.1016/j.critrevonc.2018.08.008
23. van Abbema DL, van den Akker M, Janssen-Heijnen ML, et al. Patient- and tumor-related predictors of chemotherapy intolerance in older patients with cancer: a systematic review. J Geriatr Oncol. 2019;10(1):31-41. doi: https://doi.org/10.1016/j.jgo.2018.04.001
24. Webster EM, Burke WM, Ware HM, et al. Patient reported outcomes in evaluation of chemotherapy toxicity in women with gynecologic malignancies: a pilot study. Gynecol Oncol. 2018;150(3):487-93. doi: https://doi.org/10.1016/j.ygyno.2018.07.008
25. Li H, Wu X, Cheng X. Advances in diagnosis and treatment of metastatic cervical cancer. J Gynecol Oncol. 2016;27(4):e43. doi: https://doi.org/10.3802/jgo.2016.27.e43
26. Krusun S, Pesee M, Supakalin N, et al. Treatment interruption during concurrent chemoradiotherapy of uterine cervical cancer; analysis of factors and outcomes. Asian Pac J Cancer Prev. 2014;15(14):5653-7. doi: https://doi.org/10.7314/apjcp.2014.15.14.5653
27. Jang TK, Kim DY, Lee SW, et al. Trends in treatment during the last stages of life in end-stage gynecologic cancer patients who received active palliative chemotherapy: a comparative analysis of 10-year data in a single institution. BMC Palliat Care. 2018;17(1):99. doi: https://doi.org/10.1186/s12904-018-0348-7
28. Muralikrishnan S, Hatzis C, Katz A, et al. Chemotherapy for elderly ovarian cancer patients. Gynecol Obstet (Sunnyvale). 2016;6(8):397. doi: https://doi.org/10.4172/2161-0932.1000397
29. Chambers LM, Son J, Radeva M, et al. Evaluation of non-completion of intraperitoneal chemotherapy in patients with advanced epithelial ovarian cancer. J Gynecol Oncol. 2019;30(6):e93. doi: https://doi.org/10.3802/jgo.2019.30.e93
30. Falandry C, Weber B, Savoye AM, et al. Development of a geriatric vulnerability score in elderly patients with advanced ovarian cancer treated with first-line carboplatin: a GINECO prospective trial. Ann Oncol. 2013;24(11):2808-13. doi: https://doi.org/10.1093/annonc/mdt360
31. Khouri OR, Frey MK, Musa F, et al. Neoadjuvant chemotherapy in patients with advanced endometrial cancer. Cancer Chemother Pharmacol. 2019;84(2):281-5. doi: https://doi.org/10.1007/s00280-019-03838-x
32. de Boer SM, Powell ME, Mileshkin L, et al. Toxicity and quality of life after adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2016;17(8):1114-26. doi: https://doi.org/10.1016/S1470-2045(16)30120-6
33. Hurria A, Togawa K, Mohile SG, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011;29(25):3457-65. doi: https://doi.org/10.1200/JCO.2011.34.7625
Recebido em 28/4/2021
Aprovado em 21/7/2021
Editora-científica: Anke Bergmann. Orcid iD: https://orcid.org/0000-0002-1972-8777
Este é um artigo publicado em acesso aberto (Open Access) sob a licença Creative Commons Attribution, que permite uso, distribuição e reprodução em qualquer meio, sem restrições, desde que o trabalho original seja corretamente citado.
©2019 Revista Brasileira de Cancerologia | Instituto Nacional de Câncer José Alencar Gomes da Silva | Ministério da Saúde