Assi H

Background: A 69-year-old male with history of stage IV left kidney clear cell carcinoma presented with 4-day history of gross hematuria, fever of 101.4 F and fatigue. He had been started on sunitinib, a VEGF Tyrosine Kinase Inhibitor (TKI) two weeks previously. Vitals were significant
for systolic BP of 160. Renal ultrasound showed perinephric hematoma. Labs were significant for platelets of 68,000, sodium of 120 and creatinine of 2.7 (baseline creatinine of 1.0). Urine sodium was less than 10 and 24 hours urine protein was 484 mg. Peripheral smear was negative for schistocytes. Renal biopsy performed after platelet infusion showed extensive interstitial inflammation with frequent eosinophils and interstitial edema, consistent with druginduced acute interstitial nephritis. He was started on oral steroids and required intermittent hemodialysis.

Discussion: This report describes the second known case of biopsy-proven sunitinib-induced acute interstitial nephritis (AIN). Similar case reports involving the VEGF-targeting drugs sorafenib (TKI), and bevacizumab (monoclonal antibody) imply a class effect. Previously reported renal adverse events of sunitinib include hypertension, proteinuria, renal insufficiency, and thrombotic microangiopathy; all present in this case except thrombotic microangiopathy. Thus, thrombocytopenia in this case may be secondary to bone marrow suppression.

Interestingly, while sunitinib is also used for the treatment of gastrointestinal stromal tumor (GIST) and pancreatic neuroendocrine tumors (PNET); thus far, cases of sunitinib-induced AIN have only been described in patients with metastatic renal cell carcinoma.

Given the risk of bleeding associated with a renal biopsy in the setting of thrombocytopenia on one hand; and the lethal complications that may ensue from delayed diagnosis and the possibility of permanent dialysis associated with AIN on the other, the decision to proceed with a renal biopsy is a controversial one and must be weighed carefully.

Conclusions: While sunitinib-induced AIN is exceedingly rare, it should be considered in patients with acute renal failure. Given the literature implicating VEGF-targeting drugs in cases of AIN, further study is required to elicit the link between the VEGF pathway and AIN.

Background: A 69-year-old male with history of stage IV left kidney clear cell carcinoma presented with 4-day history of gross hematuria, fever of 101.4 F and fatigue. He had been started on sunitinib, a VEGF Tyrosine Kinase Inhibitor (TKI) two weeks previously. Vitals were significant
for systolic BP of 160. Renal ultrasound showed perinephric hematoma. Labs were significant for platelets of 68,000, sodium of 120 and creatinine of 2.7 (baseline creatinine of 1.0). Urine sodium was less than 10 and 24 hours urine protein was 484 mg. Peripheral smear was negative for schistocytes. Renal biopsy performed after platelet infusion showed extensive interstitial inflammation with frequent eosinophils and interstitial edema, consistent with druginduced acute interstitial nephritis. He was started on oral steroids and required intermittent hemodialysis.

Discussion: This report describes the second known case of biopsy-proven sunitinib-induced acute interstitial nephritis (AIN). Similar case reports involving the VEGF-targeting drugs sorafenib (TKI), and bevacizumab (monoclonal antibody) imply a class effect. Previously reported renal adverse events of sunitinib include hypertension, proteinuria, renal insufficiency, and thrombotic microangiopathy; all present in this case except thrombotic microangiopathy. Thus, thrombocytopenia in this case may be secondary to bone marrow suppression.

Interestingly, while sunitinib is also used for the treatment of gastrointestinal stromal tumor (GIST) and pancreatic neuroendocrine tumors (PNET); thus far, cases of sunitinib-induced AIN have only been described in patients with metastatic renal cell carcinoma.

Given the risk of bleeding associated with a renal biopsy in the setting of thrombocytopenia on one hand; and the lethal complications that may ensue from delayed diagnosis and the possibility of permanent dialysis associated with AIN on the other, the decision to proceed with a renal biopsy is a controversial one and must be weighed carefully.

Conclusions: While sunitinib-induced AIN is exceedingly rare, it should be considered in patients with acute renal failure. Given the literature implicating VEGF-targeting drugs in cases of AIN, further study is required to elicit the link between the VEGF pathway and AIN.

Background: A 69-year-old male with history of stage IV left kidney clear cell carcinoma presented with 4-day history of gross hematuria, fever of 101.4 F and fatigue. He had been started on sunitinib, a VEGF Tyrosine Kinase Inhibitor (TKI) two weeks previously. Vitals were significant
for systolic BP of 160. Renal ultrasound showed perinephric hematoma. Labs were significant for platelets of 68,000, sodium of 120 and creatinine of 2.7 (baseline creatinine of 1.0). Urine sodium was less than 10 and 24 hours urine protein was 484 mg. Peripheral smear was negative for schistocytes. Renal biopsy performed after platelet infusion showed extensive interstitial inflammation with frequent eosinophils and interstitial edema, consistent with druginduced acute interstitial nephritis. He was started on oral steroids and required intermittent hemodialysis.

Discussion: This report describes the second known case of biopsy-proven sunitinib-induced acute interstitial nephritis (AIN). Similar case reports involving the VEGF-targeting drugs sorafenib (TKI), and bevacizumab (monoclonal antibody) imply a class effect. Previously reported renal adverse events of sunitinib include hypertension, proteinuria, renal insufficiency, and thrombotic microangiopathy; all present in this case except thrombotic microangiopathy. Thus, thrombocytopenia in this case may be secondary to bone marrow suppression.

Interestingly, while sunitinib is also used for the treatment of gastrointestinal stromal tumor (GIST) and pancreatic neuroendocrine tumors (PNET); thus far, cases of sunitinib-induced AIN have only been described in patients with metastatic renal cell carcinoma.

Given the risk of bleeding associated with a renal biopsy in the setting of thrombocytopenia on one hand; and the lethal complications that may ensue from delayed diagnosis and the possibility of permanent dialysis associated with AIN on the other, the decision to proceed with a renal biopsy is a controversial one and must be weighed carefully.

Conclusions: While sunitinib-induced AIN is exceedingly rare, it should be considered in patients with acute renal failure. Given the literature implicating VEGF-targeting drugs in cases of AIN, further study is required to elicit the link between the VEGF pathway and AIN.

Background: Current NCCN guidelines recommend the use of cetuximab, an EGFR monoclonal antibody, in the treatment of head and neck (H&N) cancers in combination with radiation therapy as initial treatment of locally or regionally advanced disease in patients, who are ineligible
for platinum-based therapy. It is also the standard of care in the treatment of recurrent or persistent disease with distant metastases.

Objective: Hypomagnesemia is a common side effect of cetuximab. Previous studies demonstrated that magnesium reduction was a potential marker of efficacy and outcome in the treatment of advanced colorectal cancer. We hypothesize that hypomagnesemia is also a marker of efficacy of the anti-neoplastic treatment of H&N cancer.

Methods: We retrospectively reviewed the medical records of H&N cancer patients that were treated with cetuximab between January 1, 2006 and January 1, 2016 at the Stratton VA Medical Center. Included in the study were patients aged over 20 years with stage III or IV H&N cancer who received cetuximab. Exclusion criteria included prior magnesium supplementation, history of treatment with anti-EGFR therapy, malabsorption syndromes and genetic magnesium wasting syndrome.

Results: Of the 63 patients studied, 23 developed hypomagnesemia for an overall incidence of 36.5%. The median age of diagnosis was 65 years for the hypomagnesemia group and 66 years for the nonhypomagnesemia. The patients that developed hypomagnesemia had a median survival of 27 months (95% CI, 16.3-37.6) while those that maintained normal magnesium levels had a mean survival of 20 months (95% CI, 12.3-27.7) (P = .583).

Conclusions: To our knowledge, no study has examined the predictive value of hypomagnesemia for the overall survival of H&N cancer patients treated with cetuximab that develop hypomagnesemia vs those that don’t. While data from the colorectal cancer suggest that hypomagnesemia may be used as a surrogate of efficacy for cetuximab, our data negates such correlation. Further study is required to elicit the link between cetuximab and hypomagnesemia.

Background: Current NCCN guidelines recommend the use of cetuximab, an EGFR monoclonal antibody, in the treatment of head and neck (H&N) cancers in combination with radiation therapy as initial treatment of locally or regionally advanced disease in patients, who are ineligible
for platinum-based therapy. It is also the standard of care in the treatment of recurrent or persistent disease with distant metastases.

Objective: Hypomagnesemia is a common side effect of cetuximab. Previous studies demonstrated that magnesium reduction was a potential marker of efficacy and outcome in the treatment of advanced colorectal cancer. We hypothesize that hypomagnesemia is also a marker of efficacy of the anti-neoplastic treatment of H&N cancer.

Methods: We retrospectively reviewed the medical records of H&N cancer patients that were treated with cetuximab between January 1, 2006 and January 1, 2016 at the Stratton VA Medical Center. Included in the study were patients aged over 20 years with stage III or IV H&N cancer who received cetuximab. Exclusion criteria included prior magnesium supplementation, history of treatment with anti-EGFR therapy, malabsorption syndromes and genetic magnesium wasting syndrome.

Results: Of the 63 patients studied, 23 developed hypomagnesemia for an overall incidence of 36.5%. The median age of diagnosis was 65 years for the hypomagnesemia group and 66 years for the nonhypomagnesemia. The patients that developed hypomagnesemia had a median survival of 27 months (95% CI, 16.3-37.6) while those that maintained normal magnesium levels had a mean survival of 20 months (95% CI, 12.3-27.7) (P = .583).

Conclusions: To our knowledge, no study has examined the predictive value of hypomagnesemia for the overall survival of H&N cancer patients treated with cetuximab that develop hypomagnesemia vs those that don’t. While data from the colorectal cancer suggest that hypomagnesemia may be used as a surrogate of efficacy for cetuximab, our data negates such correlation. Further study is required to elicit the link between cetuximab and hypomagnesemia.

Background: Current NCCN guidelines recommend the use of cetuximab, an EGFR monoclonal antibody, in the treatment of head and neck (H&N) cancers in combination with radiation therapy as initial treatment of locally or regionally advanced disease in patients, who are ineligible
for platinum-based therapy. It is also the standard of care in the treatment of recurrent or persistent disease with distant metastases.

Objective: Hypomagnesemia is a common side effect of cetuximab. Previous studies demonstrated that magnesium reduction was a potential marker of efficacy and outcome in the treatment of advanced colorectal cancer. We hypothesize that hypomagnesemia is also a marker of efficacy of the anti-neoplastic treatment of H&N cancer.

Methods: We retrospectively reviewed the medical records of H&N cancer patients that were treated with cetuximab between January 1, 2006 and January 1, 2016 at the Stratton VA Medical Center. Included in the study were patients aged over 20 years with stage III or IV H&N cancer who received cetuximab. Exclusion criteria included prior magnesium supplementation, history of treatment with anti-EGFR therapy, malabsorption syndromes and genetic magnesium wasting syndrome.

Results: Of the 63 patients studied, 23 developed hypomagnesemia for an overall incidence of 36.5%. The median age of diagnosis was 65 years for the hypomagnesemia group and 66 years for the nonhypomagnesemia. The patients that developed hypomagnesemia had a median survival of 27 months (95% CI, 16.3-37.6) while those that maintained normal magnesium levels had a mean survival of 20 months (95% CI, 12.3-27.7) (P = .583).

Conclusions: To our knowledge, no study has examined the predictive value of hypomagnesemia for the overall survival of H&N cancer patients treated with cetuximab that develop hypomagnesemia vs those that don’t. While data from the colorectal cancer suggest that hypomagnesemia may be used as a surrogate of efficacy for cetuximab, our data negates such correlation. Further study is required to elicit the link between cetuximab and hypomagnesemia.