Capecitabine and Celecoxib as a Promising Therapy for Thymic Neoplasms

Wood, Kevin; Byron, Elizabeth; Janisch, Linda; Salgia, Ravi; Sharma, Manish

doi:10.1097/coc.0000000000000400

Cited by 5 publications

(2 citation statements)

References 16 publications

(16 reference statements)

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“…Toxicities observed were as expected for capecitabine. We previously reported durable responses to the combination in the subgroup of patients with thymic malignancies …”

Section: Resultsmentioning

confidence: 99%

Prolonged Pharmacokinetic Interaction Between Capecitabine and a CYP2C9 Substrate, Celecoxib

Ramı́rez

House

Karrison

et al. 2019

The Journal of Clinical Pharma

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This study investigated the time course and magnitude of the pharmacokinetic interaction between capecitabine and the cytochrome P450 (CYP) 2C9 substrate celecoxib, with implications for coadministration of fluoropyrimidines with CYP2C9 substrates such as warfarin. Patients received celecoxib 200 mg orally twice daily continuously, with capecitabine (1000 mg/m2 orally twice daily for 14 days every 21 days) starting 7 days later. Assessment of the drug‐drug interaction (DDI) potential was performed using equivalence testing, which assumes that there is no clinically relevant DDI when the calculated 90% confidence intervals (CIs) of the drug exposure ratios fall within the range of 0.80 to 1.25. Comparison of steady‐state pharmacokinetic parameters of celecoxib between day 7 (cycle 0, celecoxib only) and day 14 (cycle 1, celecoxib + capecitabine) showed geometric mean ratios of 1.24 (90%CI, 1.04‐1.49), 1.30 (1.11‐1.53) and 1.28 (1.11‐1.47) for maximum plasma concentration, minimum plasma concentration, and area under the concentration‐time curve from time zero to 8 hours, respectively. Comparison of day 7 vs day 21 (cycle 1, after 1 week washout of capecitabine) showed a further increase in the geometric mean ratio of maximum plasma concentration (1.39; 90%CI, 1.16‐1.66), minimum plasma concentration (1.53; 1.10‐2.12) and area under the concentration‐time curve from time zero to 8 hours (1.41; 1.19‐1.68). Because the 90%CIs fell outside the prespecified equivalence margin, we conclude that coadministration results in a DDI (increased celecoxib exposure) that persists for at least 7 days after capecitabine discontinuation. Close monitoring should be undertaken when administering fluoropyrimidines with CYP2C9 substrates with narrow therapeutic indexes while also weighing the benefits and risks for individual patients.

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“…Toxicities observed were as expected for capecitabine. We previously reported durable responses to the combination in the subgroup of patients with thymic malignancies …”

Section: Resultsmentioning

confidence: 99%

Prolonged Pharmacokinetic Interaction Between Capecitabine and a CYP2C9 Substrate, Celecoxib

Ramı́rez

House

Karrison

et al. 2019

The Journal of Clinical Pharma

Self Cite

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“…A recent study, on which our treatment plan was based, demonstrated some success in treating metastatic thymic epithelial neoplasms with capecitabine 1000 mg/m 2 two times per day and celecoxib 200 mg two times per day for 14 days on a 21-day cycle. Three patients in that study had thymic carcinomas, of which two had a complete response to therapy and one had a partial response 7…”

Section: Discussionmentioning

confidence: 96%

Metastatic basaloid squamous cell carcinoma of thymic origin

Phen¹,

Wang

Kelling

et al. 2019

BMJ Case Rep

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A 57-year-old man with a known anterior mediastinal mass presented with abdominal distension, jaundice, and signs of urinary and bowel obstruction. Labs revealed leukocytosis, transaminitis, direct hyperbilirubinaemia and elevated levels of alkaline phosphatase, lactate dehydrogenase and uric acid. Subsequent imaging revealed the anterior mediastinal mass and diffuse liver lesions consistent with metastatic disease. MRI of the spine and brain were negative for metastases. Liver biopsy and immunohistochemistry revealed basaloid squamous cell carcinoma of thymic origin. Treatment with capecitabine was initiated but was complicated by worsening liver and kidney failure. Eventually, due to continued worsening of the patient’s condition and minimal treatment response, capecitabine was stopped during cycle 1 and the patient was discharged to inpatient hospice with comfort care. In this case report, we highlight the presenting features, imaging findings and management of a patient with metastatic thymic carcinoma.

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