5-Fluorouracil and Capecitabine: Assessment and Treatment of Uncommon Early-Onset Severe Toxicities Associated With Administration

Brutcher, Edith; Christensen, Deb; Smith, Melissa H; Koutlas, Judy B; Sellers, Jean B.; Timmons, Tahitia; Thompson, Joanna B.

doi:10.1188/18.cjon.627-634

“…Capecitabine is an oral prodrug of 5-fluorouracil (5-FU) used as monotherapy, concurrently with radiation, or in combination with other antineoplastic agents for multiple gastrointestinal (GI) tract malignancies, including colorectal, gastroesophageal and pancreatobiliary cancers [ 1 - 4 ]. In contrast to infusional 5-FU, capecitabine obviates the need for an indwelling port and 46-h infusion, but it carries potential toxicities that can be life-threatening if not treated early [ 4 ]. The most common side-effects of capecitabine when given at full systemic doses (1000 mg/m 2 b.i.d.…”

Section: Introductionmentioning

confidence: 99%

Racial and ethnic differences in capecitabine toxicity in patients with gastrointestinal tract cancers

Brazelton¹

2022

aog

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Background Capecitabine is used as a first-line treatment for gastrointestinal (GI) tract cancers. Common toxicities of capecitabine include diarrhea and hand-foot syndrome, which frequently require dose reduction, interruption, or discontinuation. While racial and ethnic differences in capecitabine toxicities have been suggested, they have not been evaluated in a diverse “real-world” setting. We examined differences in capecitabine-related toxicities in different racial and ethnic populations. Methods The electronic medical records of patients receiving first-line capecitabine-containing regimens for GI malignancies were reviewed. Patients on irinotecan-containing regimens or radiation were excluded because of overlapping toxicities. Multiple logistic regression models were used to test the association between race or ethnicity and capecitabine toxicities while adjusting for other demographic characteristics. Results One hundred twenty-five patients diagnosed with colon (N=76, 60.8%), rectal (N=22, 17.6%), gastric (N=16, 12.8%), or other GI cancers (N=11, 8.8%) were included. In logistic regression analysis, diarrhea occurrence was significantly lower in the African-American/non-Hispanic (odds ratio [OR] 0.25, 95% confidence interval [CI] 0.08-0.75; P=0.01) compared to Caucasian non-Hispanic population. The occurrence of dose-reduction was significantly higher in the African-American/non-Hispanic population (OR 5.83, 95%CI 1.49-22.80; P=0.01) and in the Caucasian/Hispanic population (OR 4.49, 95%CI 1.09-18.42; P=0.03) compared to Caucasian non-Hispanic population. Conclusions We have identified racial and ethnic differences in the incidence of capecitabine toxicities, which may help clinicians counsel patients with GI malignancies on capecitabine. There is a need for prospective studies to confirm our findings and to understand the relationship between the incidence of toxicities and dose reductions or discontinuation.

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“…In the present study, CAPTEM showed significant benefits in clinical efficiency and the enhancement of hormone levels and pituitary function. CAP is an alternative drug to 5-F uracil (5-FU) that acts in tumor tissue catalyzed by thymidine phosphorylase to 5-FU [ 20 ]. It has been reported that CAPTEM demonstrated significant activity in the treatment of neuroendocrine tumors (NETs), particularly in pancreatic NETs, with ORRs ranging from 30% to 70% and improved PFS and overall survival (OS) of patients [ 21 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

Chemotherapy of Capecitabine plus Temozolomide for Refractory Pituitary Adenoma after Tumor Resection and Its Impact on Serum Prolactin, IGF-1, and Growth Hormone

Wang

¹

,

Hu

²

,

Li

³

et al. 2022

Journal of Oncology

1

0

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Objective. To investigate the efficiency of capecitabine (CAP) plus temozolomide (TEM) in refractory pituitary adenoma after tumor resection and its impact on serum prolactin (PRL), insulin-like growth factor 1 (IGF-1), and growth hormone (GH) levels. Methods. From January 2017 to January 2020, 80 patients assessed for eligibility receiving transsphenoidal tumor resection for refractory pituitary adenoma in the Department of Neurosurgery of our hospital were recruited. They were randomly distributed at a ratio of 1 : 1 via the random number table method to receive either bromocriptine and TEM (control group) or bromocriptine plus combination chemotherapy of TEM and CAP (study group). The two groups were compared in terms of clinical efficacy and serum levels of PRL, IGF-1, and GH. Results. The objective response rate (ORR) was 87.50% and 67.50% in the study group and the control group, respectively P = 0.032 . Before treatment, two groups had similar levels of PRL, IGF-1, and GH. After treatment, PRL levels in the study group were lower than that in the control group (278.35 ± 39.25 versus 326.35 ± 42.45, P < 0.001 ). Compared with the control group, IGF-1 levels in the study group were also lower (311.78 ± 28.82 versus 364.35 ± 31.35, P < 0.001 ). The study group presented markedly lower levels of thyroid-stimulating hormone (TSH) and higher serum levels of free thyroxine-4 (FT-4) and adrenocorticotropic hormone (ACTH) versus the control group P < 0.05 . The incidence of adverse events was comparable between the study group (30.0%) and the control group (22.5%) P > 0.05 . All eligible patients had similar progression-free survival (PFS) after chemotherapy. Conclusion. For patients with refractory pituitary adenoma, the combination chemotherapy of CAP and TEM significantly improves clinical outcomes and corrects hormonal disturbances, with a good safety profile, but its long-term efficacy requires further investigation.

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“…Drugs with high toxicity, such as mitomycin C and 5-fluorouracil, were included in the present review for a comprehensive discussion. As will be discussed later, mitomycin C could cause bone marrow depression [ 19 ]; 5-fluorouracil is associated with gastrointestinal (e.g., diarrhea), hematological (e.g., neutropenia, thrombocytopenia, anemia), and dermal (e.g., hand–foot syndrome) undesirable side effects [ 20 ]. Although the toxicity of drugs should be carefully evaluated and toxic drugs should be avoided, this is often not possible.…”

Section: Introductionmentioning

confidence: 99%

“…Despite the overall safety of 5-fluorouracil, this drug is toxic in some cases, with toxicities including gastrointestinal (e.g., diarrhea, nausea, vomiting, mucositis/stomatitis, anorexia), hematological (e.g., neutropenia, thrombocytopenia, anemia), and dermal (e.g., hand–foot syndrome) symptoms [ 20 ]. A meta-analysis involving 1219 patients with colorectal cancer receiving 5-fluorouracil intravenously (either by bolus or infusion) showed that 31%–34% of the patients had grade 3 to 4 toxicities as defined by the WHO, with 0.5% of the patients experiencing lethal toxicity [ 45 ].…”

Section: Introductionmentioning

confidence: 99%

Can Drug Repurposing be Effective Against Carbapenem-Resistant Acinetobacter baumannii?

Gontijo

¹

,

Pereira

²

,

Bonfante

³

2021

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Carbapenem-resistant Acinetobacter baumannii has been classified as a top priority for the development of new therapies due to its resistance to most antibiotics. Drug repurposing may be a fast and inexpensive strategy for treating this pathogen. This review aims to critically evaluate repurposed drugs for the treatment of infections caused by carbapenem-resistant A. baumannii , correlating their antimicrobial activity with data available for toxicity and side effects. Some drugs have been suggested as promising candidates for repurposing; however, in some cases, high toxicity and low plasma concentrations reduce applicability in clinical practice. The most favorable applicability is offered by fusidic acid and colistin, possibly combined with a third agent, promising to be well tolerated and achieving satisfactory plasma concentrations.

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5-Fluorouracil and Capecitabine: Assessment and Treatment of Uncommon Early-Onset Severe Toxicities Associated With Administration

Cited by 7 publications

References 0 publications

Racial and ethnic differences in capecitabine toxicity in patients with gastrointestinal tract cancers

Racial and ethnic differences in capecitabine toxicity in patients with gastrointestinal tract cancers

Chemotherapy of Capecitabine plus Temozolomide for Refractory Pituitary Adenoma after Tumor Resection and Its Impact on Serum Prolactin, IGF-1, and Growth Hormone

Can Drug Repurposing be Effective Against Carbapenem-Resistant Acinetobacter baumannii?

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