Xeloda for Metastatic Triple Negative Breast Cancer Review
ane Introduction
Breast cancer is one of the most commonly diagnosed cancers and the leading cause of cancer death among females worldwide.[1] Triple-negative breast cancer (TNBC) is a special blazon of breast cancer, which lacks expression of estrogen receptor (ER), progesterone receptor (PR), and HER2 gene. TNBC accounts for 15% to 20% of newly diagnosed BC cases.[2] Because of lacking recognized therapeutic molecular biological science targets, the treatment of TNBC is peculiarly challenging. Unfortunately, TNBC is highly proliferative and aggressiveness, rapid disease progression, loftier adventure for recurrence, and poor prognosis.[3] Chemotherapy is the mainstay of TNBC's treatment at present,[four] and novel strategies and drugs are urgently needed.
Angiogenesis is i of the hallmarks of cancer,[v] which is vital for tumor growth, development, and metastasis. Anti-angiogenesis is an important anticancer strategy.[6] Vascular endothelial growth cistron (VEGF) signaling plays an important function in angiogenesis via activation of VEGF receptor (VEGFR).[six] The VEGFR family unit involves 3 molecular subtypes (VEGFR-1, VEGFR-2, and VEGFR-3), which are type-Ii transmembrane proteins characterized past a tyrosine kinase (TK) action.[seven] Amongst them, VEGFR-ii is the majorly implicated in the pathological overformation of claret vessels in the context of several solid tumors.[viii]
Apatinib is a novel small molecule receptor TK inhibitor selectively targeting VEGFR 2 (VEGFR-2).[nine] Recently, apatinib has demonstrated its satisfying efficacy on diverse types of cancers such equally gastric cancer,[10] breast cancer,[11] and nasopharyngeal carcinoma.[12] At the aforementioned time, it also has shown acceptable toxicities.
Capecitabine (Xeloda) is an oral fluoropyrimidine carbamate that undergoes sequential conversion to five-fluorouracil (5-FU).[thirteen] The conversion to 5-FU occurs in several steps, and the last enzyme in the pathway is thymidine phosphorylase, which is located at much higher concentrations in tumor tissue than in normal tissues, the agile form of the drug is mainly present at the tumor site.[xiv] In addition, capecitabine typically lacks cumulative toxicity with prolonged employ, so is suitable for long-term administration. A number of studies accept indicated that capecitabine is constructive for the handling of metastatic breast cancer equally a single agent or as part of a combination regimen.[15,16] However, at that place is no study on the efficacy and safety of combination therapy of apatinib and capecitabine in the handling of avant-garde TNBC equally the 3rd-line treatment.
In this retrospective written report, we aimed to explore the efficacy and rubber of apatinib and capecitabine as the third-line treatment for advanced TNBC.
2 Patients and methods
ii.one Patients
This study was a retrospective assay, which included 44 avant-garde TNBC patients who failed in first-line or second-line therapy in Tangshan People's Hospital from January 2016 to February 2017. Amidst them, 22 patients received apatinib and capecitabine as tertiary-line therapy, while another 22 patients treated with capecitabine monotherapy served as control. The two groups were matched in age, Karnofsky operation score (KPS), metastatic site, and history of chemotherapy. The inclusion criteria were as follows: age ≥eighteen years; definite pathological diagnosis; failure of first-line or 2nd-line; KPS≥80; and life expectancy ≥three months.
2.two Drug assistants
In apatinib and capecitabine group, apatinib, 500 mg, was orally administered daily on days 1 through 28 of each 4-calendar week wheel. Capecitabine, at 12,500 mg/mii, was orally taken twice daily for 14 days followed past a vii-day rest period until affliction progression. In capecitabine group, an oral dose of capecitabine 1250 mg/yard2 was taken twice daily for 14 days followed by a 7-mean solar day rest period until affliction progression.
2.iii Efficacy and safety assessments
The primary end point of our report was PFS, defined as the time from enrollment to documented tumor progression with computed tomography (CT)/magnetic resonance imaging (MRI) scan or death equally a result of any cause, whichever occurred get-go. The secondary end points were ORR (CR +PR), DCR (CR+PR+SD), and toxicity.
Treatment efficacy was evaluated in accordance with the Response Evaluation Criteria in Solid Tumors, which were classified into complete response (CR), partial response (PR), stable affliction (SD), and progressive illness (PD). Adverse events were assessed and graded according to the National Cancer Institute Common Toxicity Criteria version 3.0 and classified as caste 0∼ 4.
2.four Ethical statement
The study was approved by the institutional ideals commission of Tangshan People's Hospital. All procedures performed in this study were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
2.5 Statistical analysis
Pearson ten 2 test or Fisher exact test was used to clarify the baseline characteristics, treatment efficacy, and adverse events. The t examination was used to compare the clinical parameters between both groups. Survival analysis was done co-ordinate to Kaplan–Meier method. Data were expressed equally the hateful ± standard deviation and P < .05 was considered statistically meaning. The SPSS (Statistical Package for the Social Science, SPSS Inc., Chicago, IL) version sixteen.0 or GraphPad Prism (GraphPad Software, San Diego, CA) version 5.0 was used for all statistical analyses.
3 Results
three.one Baseline characteristics
This retrospective accomplice involved 44 advanced TNBC patients fulfilling the inclusion criteria during the menses from Jan 2016 till Feb 2017. Among them, 22 patients received apatinib and capecitabine, while 22 patients received capecitabine monotherapy. The characteristics of the patients are summarized in Tabular array 1. At that place was no significant departure in historic period, KPS, and disease characteristics between the apatinib and capecitabine group and the capecitabine grouping.
Characteristics of patients with avant-garde triple-negative breast cancer patients.
three.ii Treatment efficacy
Median follow-up fourth dimension was v months (range, 2–11 months). The median PFS time of patients in apatinib and capecitabine group was five.5 months, and for the capecitabine group, was 3.5 months (Fig. 1). The apatinib and capecitabine group exhibited a college PFS than capecitabine group [P = .001, run a risk ratio (HR) = 0.2583, 95% confidence interval (95% CI) 0.1150–0.5803].
Kaplan–Meier curves of progression-free survival (PFS). The median PFS time of patients in apatinib and capecitabine group was v.v months, and for the capecitabine group was iii.5 months (P = .001).
Of the total 44 patients, no patient was rated every bit having CR. In apatinib and capecitabine grouping, nine patients (40.nine%) were rated as having a PR, 6 patients (27.3%) were rated every bit having a SD, and seven patients (31.8%) had a PD. ORR was forty.ix%, and DCR was 68.2%. In capecitabine group, 3 patients (13.iv%) were rated as having a PR, 4 patients (eighteen.2%) were rated every bit having a SD, and 15 patients (68.2%) had a PD. ORR was 13.4%, and DCR was 31.viii%. The ORR and DCR in apatinib and capecitabine grouping were better than in capecitabine group (P = .042; .016). There was a meaning difference betwixt the ii groups. The apatinib and capecitabine regimen had a meliorate efficacy than capecitabine regimen. The clinical response rates are listed in the Table 2.
Comparing of efficacy betwixt the apatinib and capecitabine group and the capecitabine group (n, %).
three.iii Agin events
Previous studies have reported that the main toxicities of apatinib were hypertension, proteinuria, liver dysfunction, hand–pes syndrome, thrombocytopenia, leukopenia, and neutropenia, which by and large manageable.[eleven,17] As presented in Tabular array three, the most mutual adverse events in the patients were hypertension, neutropenia, leukopenia, fatigue, bleeding, nausea, and hand–pes syndrome. Among the ii groups, nigh of adverse events were degree I-II, which were not serious. In that location was no significant departure in the adverse events such as hypertension, neutropenia, leukopenia, fatigue, nausea, paw–human foot syndrome, or degree III-IV adverse consequence of haemorrhage betwixt the 2 groups. Although the apatinib and capecitabine group showed higher incidence of caste I-2 bleeding than the capecitabine group (P = .021), this degree I-II adverse upshot was manageable and non serious, which had no clinical significance.
Comparison of adverse events between the apatinib and capecitabine group and the capecitabine group (n, %).
four Discussion
TNBC is a heterogeneous disease and associated with a higher risk of early on relapse with visceral metastasis.[18] Because of uncommonness, aggressiveness, and impressive heterogeneity, the treatment of TNBC remains a major clinical claiming,[19] especially for the patients who failed in starting time-line or second-line therapy. Although a swell deal of therapies have been developed to specific molecular targets, such every bit poly-(ADP-ribose)-polymerase inhibitors, epidermal growth gene receptor inhibitors, Src TK inhibitors, and mTOR inhibitors,[twenty] chemotherapy is all the same the mainstay of treatment.
Capecitabine has been approved for the treatment of breast cancer,[21] and information technology is widely used in metastatic breast cancer. Information technology has been proved effective for the treatment of metastatic breast cancer in a number of Phase I, Phase Two, and Stage III trials.[22–24] A retrospective study including 363 patients with TNBC treated with capecitabine demonstrated that capecitabine is a treatment option for patients with TNBC in advanced disease including first-line and second/third-line.[25]
Apatinib is an oral, highly strong TK inhibitor targeting VEGFR2. It Antitumor activity has been demonstrated beyond a broad range of malignancies, including gastric, colorectal, and chest cancer, and proficient tolerability in phase I written report conducted in former studies.[26,27] A nonclinical trial has confirmed the encouraging efficacy and manageable prophylactic of apatinib on pretreated metastatic breast cancer patients.[17] In a multicenter stage II written report, apatinib has also been evaluated the efficacy and safe in heavily pretreated patients with metastatic TNBC.[xi]
In this study, the avant-garde TNBC patients who failed in kickoff-line or second-line therapy received apatinib and capecitabine or capecitabine monotherapy as the third-line handling. The apatinib and capecitabine grouping exhibited a higher PFS than the capecitabine group (P = .001). A retrospective report with 363 TNBC patients showed that capecitabine monotherapy achieved a ORR of 21% and a DCR of 33%[25]; our study had a like efficacy with it and the ORR in capecitabine grouping was thirteen.4%, and the DCR in capecitabine group was 31.8%. Although in apatinib and capecitabine grouping, it was forty.9% and 68.two%. The ORR and DCR in apatinib and capecitabine group were higher than that in the capecitabine grouping (P = .042; .016), which demonstrated that advanced TNBC patients with apatinib and capecitabine had a amend efficacy than those with capecitabine monotherapy.
Between the 2 groups, the most common adverse events were nausea, hand–human foot syndrome, fatigue, neutropenia, and leukopenia. Nosotros institute no significant difference in the above agin events, while the capecitabine group showed significantly lower incidence of degree I-2 bleeding than the apatinib and capecitabine group (P = .021). However, the minor bleeding events (degree I-II) were manageable; as a issue, there was no clinical significance. At the same time, no serious bleeding (caste Iii-IV) occurred in both groups. Overall, compared with capecitabine monotherapy, apatinib and capecitabine did not increment serious agin events. Both the apatinib and capecitabine and the capecitabine regimens showed expert tolerability.
In summary, the results of our present study, although retrospective, support that tertiary-line treatment of avant-garde TNBC with the apatinib and capecitabine regimen showed better efficacy and similar serious adverse events compared with capecitabine regimen. Given the limited treatment options for advanced TNBC patients who failed in first-line or 2d-line therapy, apatinib and capecitabine regimen may be one of the more effective treatments. However, our study is a single-center retrospective report with a small sample size, and more prospective studies with a big sample size are needed to verify the results of our study.
Acknowledgments
We greatly give thanks the patients, investigators, and participating institutions.
Writer contributions
Conceptualization: Yi Hui Li, Jian Gong Wang, Xiao Hong Wang.
Data curation: Yang Zhou, Yu Wei Wang, Jian Gong Wang, Xiao Hong Wang.
Formal analysis: Yang Zhou, Yu Wei Wang, Jian Gong Wang, Xiao Hong Wang.
Investigation: Yi Hui Li, Yu Wei Wang, Ling Tong, Run Xue Jiang, Jing Qi Feng.
Methodology: Yang Zhou, Lei Xiao.
Resources: Yi Hui Li, Yu Wei Wang, Ling Tong, Run Xue Jiang, Lei Xiao, Shu Shan Xing.
Software: Shu Shan Xing, Jing Qi Feng.
Supervision: Ling Tong, Guang Ju Zhang, Fang Qian.
Validation: Fang Qian, Ya Ling Zhao.
Visualization: Guang Ju Zhang, Ya Ling Zhao.
Writing – original typhoon: Yi Hui Li, Yang Zhou.
Writing – review & editing: Jian Gong Wang, Xiao Hong Wang.
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Keywords:
advanced triple-negative breast cancer; apatinib; capecitabine; tertiary-line therapy
Source: https://journals.lww.com/md-journal/fulltext/2018/09070/comparison_of_apatinib_and_capecitabine__xeloda_.84.aspx
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