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Gonzalez et al. Sunitinib effectiveness and safety in Costa Rica

INTRODUCTION Committees in each hospital approved this study.
All patients received oral sunitinib maleate, 50 mg
Renal cell carcinoma (RCC) accounts for about 3% once daily for 4 weeks of a 6-week treatment cycle
of all adult cancers, is the 8th most common cancer (4 weeks on, 2 weeks off). The dosage was reduced
in Central America and the 10th worldwide, and the in some cases to 37.5 mg daily. Sunitinib was given
clear-cell RCC (ccRCC) is its most frequent histologic until disease progression or unacceptable toxicity.
subtype. [1-4] Physical examination and clinical laboratory tests were
performed approximately one or two days before each
Surgery remains the standard of care for localized cycle. Adverse events were registered according to the
disease, and can often be curative. [5,6] Unfortunately, National Cancer Institute (NCI) common terminology
metastatic RCC (mRCC) is found in approximately Criteria for Adverse Events (CTACAE), version
one third of patients. Furthermore, RCC is extremely 3.0. Tumor evaluation was performed according
[7]
resistant to conventional chemotherapy. That is why to Response Evaluation Criteria in Solid Tumors
[8]
different treatment strategies had been developed, (RECIST) version 1.0, this assessment being done
taking into account improvements in understanding in accordance with local practices at each hospital.
RCC biology and tumor behavior. RCC is highly PFS was defined as from time of starting sunitinib to
vascularized due to overexpression of vascular disease progression or death from any cause (death
endothelial growth factor (VEGF) induced by alterations could occur within one month of the last treatment
of the tumor suppressor gene, Von Hippel-Lindau dose and was included in the PFS analysis). OS was
(VHL), leading to the increase of hypoxia-inducible defined as the time from start of sunitinib to death from
factors 1 alpha and 2 alpha, ending in angiogenesis. any cause.
[9]
This has allowed the development of VEGF inhibitors
such as tyrosine-kinase inhibitors (TKIs), monoclonal Statistical analysis
antibodies against VEGF, and mammalian target of In this retrospective study we included all patients
rapamycin (mTOR) inhibitors. [5] who received sunitinib during the observational period
of time in Costa Rica. For that reason there were
In Costa Rica the National Health Care System neither pre-specified sample sizes nor pre-established
(Caja Costarricense de Seguro Social, CCSS) has hypotheses to evaluate. Categorical variables are
authorized the use of sunitinib to treat mRCC in first presented as percentages. Continuous variables
line setting. Sunitinib is a multiple TKI, including the are presented as the mean ± standard deviation. To
[10]
VEFG receptors (VEFGRs) and platelet-derived growth assess the PFS and OS the Kaplan-Meier method
factor receptors, producing a strong antitumor action was used. A Cox Proportional Model Analysis was
in mRCC and is approved worldwide as upfront line employed to determine differences in the outcome
[11]
treatment of mRCC, with the reporting of significant variables according to age less or higher than 65 year.
objective response rates and also superiority over In addition univariate and multivariate analyses were
interferon-alfa in progression-free survival (PFS), with used to explore the association between OS and PFS
a trend to increase overall survival (OS). [12,13] with prognostic factors. A P value less than 0.05 was
considered statistically significant. Data were analyzed
In this retrospective study we evaluated the using SPSS for Mac version 20.0 (SPSS, Chicago, IL).
effectiveness of sunitinib in the Costa Rican population
in terms of median overall survival (mOS), median RESULTS
progression free survival (mPFS) and its safety profile.
A total of 77 patients were included in the study. Patient
METHODS characteristics are described in Table 1. All patients
received sunitinib as first line treatment, while none
Patients and study design was previously treated either with cytokines or TKIs.
This is a retrospective study reviewing the medical With a median follow-up of 18.9 months, mPFS was
records from a total of 77 patients treated with sunitinib 13.7 months [95% confidence interval (CI): 11.24-
as first-line therapy in mRCC. Data were collected 16.16 months], and mOS was 21.0 months (95% CI:
between February 2007 and June 2015 in the three 13.42-28.58 months) [Figure 1].
major hospitals (Hospital San Juan de Dios, Hospital
Calderon Guardia and Hospital Mexico) in San Jose, A statistically significant difference was found in
Costa Rica. All patients were required to be at least terms of PFS and OS according to patient age, risk of
18 years of age and to have histologically confirmed progression as well as risk of death by disease. This
mRCC (regardless of histologic subtype). The Ethics was higher in patients 65 years or older in comparison
Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ October 21, 2016 397