Gastric perforation related to concurrent use of nintedanib and ramucirumab

Takahashi, Saeko; Murata, Saori; Yoshino, Yudai; Kobayashi, Yasuhiko; Nakamura, Morio

doi:10.1002/rcr2.383

Cited by 3 publications

(3 citation statements)

References 3 publications

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“…Likewise, several case studies in humans have reported anastomotic leak in the bowel following initiation of TKIs. 13-18 We now infer a similar contributory mechanism of TKIs to the development of gastropharyngeal leak in our patient. While the exact mechanism of action of this side effect is unclear, we look to the evidence of other animal studies as a possible starting point for an answer.…”

Section: Discussionsupporting

confidence: 62%

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Gastropharyngeal Anastomotic Leak in Medullary Thyroid Carcinoma Following Initiation of a Tyrosine Kinase Inhibitor: A Case Report of an Unusual Side Effect of Cabozantinib

Ackerman

Kent

Walker

2020

Ann Otol Rhinol Laryngol

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Background: Medullary thyroid carcinoma (MTC) accounts for 1% to 2% of thyroid cancers in the United States. When identified early, total thyroidectomy is most often curative. However, in advanced disease, more aggressive treatment such as laryngectomy and esophagectomy may be indicated. Postsurgical fistula formation and leak is a potential complication in such cases. These fistulas are most likely to occur at the anastomotic site in cases of laryngectomy or esophagectomy. Concomitant chemotherapy and radiation increase this risk. Tyrosine kinase inhibitors (TKI) such as Cabozantinib are used as therapy for metastatic MTC. These drugs have previously been associated with dehiscence of anastomotic sites in the gastrointestinal tract. While previously identified in the bowel, this report represents the first documented case of gastropharyngeal anastomosis leak described in the context of TKI use for head and neck cancer. Case Presentation: We present the case of a 72-year-old male previously diagnosed with MTC. His gastropharyngeal anastomosis status-post laryngopharyngectomy and gastric pull up had been stable for 23 years. Over the past year, he developed back pain and was found to have spinal metastases of MTC. He was subsequently started on Cabozantinib to slow the progression of the disease. Within months of starting this TKI, a bleeding pharyngocutaneous fistula developed at the anastomosis site of the gastric pull up and pharynx. Upon discontinuation of Cabozantinib, the fistula healed with no further complications. Conclusions: To our knowledge, this is the first documented case of gastropharyngeal anastomotic leak related to TKI use. A causal relationship is highly plausible given the previously stable anastomosis and the suspicious advent of complications within months of initiation of this new drug. While previously limited to cases of intraabdominal bowel dehiscence, this report now suggests that wound dehiscence must be considered a known side effect of TKIs throughout the gastrointestinal tract, including the gastropharynx. As such, the risk of anastomotic dehiscence should be discussed with the patient prior to starting a TKI.

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Section: Discussionsupporting

confidence: 62%

“…More recently, gastric perforations have also been described with use of the newer TKIs Nintedanib, Ramucirumab, and Regorafenib. 17,18…”

Section: Introductionmentioning

confidence: 99%

Gastropharyngeal Anastomotic Leak in Medullary Thyroid Carcinoma Following Initiation of a Tyrosine Kinase Inhibitor: A Case Report of an Unusual Side Effect of Cabozantinib

Ackerman

Kent

Walker

2020

Ann Otol Rhinol Laryngol

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“…We found 29 completed studies evaluating FGFR -targeting drugs in 11 of 14 cancer types analyzed in the off-label estimations (Table 2). 12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38 There were 8 (27.6%) case reports, 1 (3.4%) case series, 9 (31.0%) phase 1 studies, 2 (6.9%) phase 1/2 studies, and 9 (31.0%) phase 2 studies. While 2 phase 2 trials (22.2%) were randomized, the rest were noncomparator trials.…”

Section: Resultsmentioning

confidence: 99%

Estimation of Percentage of Patients With Fibroblast Growth Factor Receptor Alterations Eligible for Off-label Use of Erdafitinib

et al. 2019

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IMPORTANCE When a novel drug is granted accelerated approval, both its on-label and off-label uses must be taken into account. OBJECTIVES To estimate the potential upper bound of off-label use of erdafitinib to treat advanced cancer with fibroblast growth factor receptor gene (FGFR) alterations, compare it to the upper bound of on-label use in urothelial cancer, and to review studies that may support off-label use. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study used frequency data on FGFR alterations by cancer type and the estimated number of deaths from all cancers for 2019 in the United States. Mortality statistics were used as surrogates for patients with advanced cancer. Analysis was conducted in May 2019. EXPOSURE Percentage of patients with an FGFR2 or FGFR3 alteration. MAIN OUTCOMES AND MEASURES Estimated number of patients with advanced cancer expressing an FGFR2 or FGFR3 alteration eligible for off-label use of erdafitinib by cancer type; number of studies investigating FGFR-targeting drugs for patients with cancer; and number of ongoing clinical trials on erdafitinib by cancer type. RESULTS A total of 15 cancer types had reported FGFR alterations. Of 455 440 estimated patients who died of cancer in 2019, 17 019 (3.7%) were estimated to have FGFR2 or FGFR3 alterations. Of these patients, 12 955 (76.1%) could be eligible for off-label treatment with erdafitinib. A total of 29 completed studies evaluated FGFR-targeting drugs in 11 cancer types, and 10 ongoing studies are studying erdafitinib for different oncological indications. CONCLUSIONS AND RELEVANCE This study indicates that the potential for off-label use of FGFR inhibitors such as erdafitinib spans a number of cancer types and a large patient population. Systematic trials exploring off-label uses may be desirable for drugs that target clear, identifiable molecular alterations because this may be more efficient than off-label use in identifying clinical scenarios where the agent has activity.

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Nintedanib/prednisolone/ramucirumab

2019

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Gastric perforation related to concurrent use of nintedanib and ramucirumab

Cited by 3 publications

References 3 publications

Gastropharyngeal Anastomotic Leak in Medullary Thyroid Carcinoma Following Initiation of a Tyrosine Kinase Inhibitor: A Case Report of an Unusual Side Effect of Cabozantinib

Gastropharyngeal Anastomotic Leak in Medullary Thyroid Carcinoma Following Initiation of a Tyrosine Kinase Inhibitor: A Case Report of an Unusual Side Effect of Cabozantinib

Estimation of Percentage of Patients With Fibroblast Growth Factor Receptor Alterations Eligible for Off-label Use of Erdafitinib

Nintedanib/prednisolone/ramucirumab

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