Banaszynski M

Background: This case describes severe transaminitis resulting 21 days after administration of the first dose of nivolumab 480 mg for non-small cell lung cancer (NSCLC) adenocarcinoma. The patient was an 81-year-old male whose disease had progressed after 3 cycles of carboplatin/pemetrexed. Molecular tumor marker testing did not reveal any actionable mutations prior to treatment.

Case Report: The patient initially presented with headaches, worsening shortness of breath and Grade 4 transaminitis (AST/ALT > 10x ULN). During hospitalization, he was treated with PO prednisone and IV methylprednisolone with a decrease in transaminases. Due to ongoing psychoses and worsening myopathies, the steroid doses were reduced. On day 14 of hospitalization, mycophenolate mofetil (MMF) 500 mg PO BID was initiated due to steroid refractory transaminitis. The patient was put on infection prophylaxis with sulfamethoxazole/trimethoprim and fluconazole at the time of MMF initiation. Valacyclovir was initiated when MMF was increased to 1,000 mg PO BID after three days without a response to lower doses. Ultimately the patient expired from cardiac failure 18 days after
hospitalization.

Discussion: Nivolumab recently received US Food and Drug Administration approval for every 4-week dosing based on pharmacokinetic data. Without clinical evidence, it was concluded that this increased dosing would not differ in safety or efficacy from previously approved doses, despite steady-state peak and average time concentrations predicted to be higher than the every 2-week dosing regimen. Both the National Comprehensive Cancer Network and American Society of Clinical Oncology recommend initiation of MMF for steroid refractory irAE transaminitis. These recommendations are based on case reports in patients receiving ipilimumab or nivolumab. The specific dosing and timing of initiation is not well elucidated. Additionally, there are case reports of use of antithymocyte globulin for management of irAEs.

Conclusions: Administration of 480-mg nivolumab may lead to more rapid onset of severe transaminitis. Administration of this dosing should be delayed until a patient demonstrates tolerability to the 240-mg dosing. High-dose steroids, in combination with MMF may provide more rapid clinical improvement. All patients on increased doses of immunosuppressive agents should receive opportunistic infection prophylaxis.

Background: This case describes severe transaminitis resulting 21 days after administration of the first dose of nivolumab 480 mg for non-small cell lung cancer (NSCLC) adenocarcinoma. The patient was an 81-year-old male whose disease had progressed after 3 cycles of carboplatin/pemetrexed. Molecular tumor marker testing did not reveal any actionable mutations prior to treatment.

Case Report: The patient initially presented with headaches, worsening shortness of breath and Grade 4 transaminitis (AST/ALT > 10x ULN). During hospitalization, he was treated with PO prednisone and IV methylprednisolone with a decrease in transaminases. Due to ongoing psychoses and worsening myopathies, the steroid doses were reduced. On day 14 of hospitalization, mycophenolate mofetil (MMF) 500 mg PO BID was initiated due to steroid refractory transaminitis. The patient was put on infection prophylaxis with sulfamethoxazole/trimethoprim and fluconazole at the time of MMF initiation. Valacyclovir was initiated when MMF was increased to 1,000 mg PO BID after three days without a response to lower doses. Ultimately the patient expired from cardiac failure 18 days after
hospitalization.

Discussion: Nivolumab recently received US Food and Drug Administration approval for every 4-week dosing based on pharmacokinetic data. Without clinical evidence, it was concluded that this increased dosing would not differ in safety or efficacy from previously approved doses, despite steady-state peak and average time concentrations predicted to be higher than the every 2-week dosing regimen. Both the National Comprehensive Cancer Network and American Society of Clinical Oncology recommend initiation of MMF for steroid refractory irAE transaminitis. These recommendations are based on case reports in patients receiving ipilimumab or nivolumab. The specific dosing and timing of initiation is not well elucidated. Additionally, there are case reports of use of antithymocyte globulin for management of irAEs.

Conclusions: Administration of 480-mg nivolumab may lead to more rapid onset of severe transaminitis. Administration of this dosing should be delayed until a patient demonstrates tolerability to the 240-mg dosing. High-dose steroids, in combination with MMF may provide more rapid clinical improvement. All patients on increased doses of immunosuppressive agents should receive opportunistic infection prophylaxis.

Background: This case describes severe transaminitis resulting 21 days after administration of the first dose of nivolumab 480 mg for non-small cell lung cancer (NSCLC) adenocarcinoma. The patient was an 81-year-old male whose disease had progressed after 3 cycles of carboplatin/pemetrexed. Molecular tumor marker testing did not reveal any actionable mutations prior to treatment.

Case Report: The patient initially presented with headaches, worsening shortness of breath and Grade 4 transaminitis (AST/ALT > 10x ULN). During hospitalization, he was treated with PO prednisone and IV methylprednisolone with a decrease in transaminases. Due to ongoing psychoses and worsening myopathies, the steroid doses were reduced. On day 14 of hospitalization, mycophenolate mofetil (MMF) 500 mg PO BID was initiated due to steroid refractory transaminitis. The patient was put on infection prophylaxis with sulfamethoxazole/trimethoprim and fluconazole at the time of MMF initiation. Valacyclovir was initiated when MMF was increased to 1,000 mg PO BID after three days without a response to lower doses. Ultimately the patient expired from cardiac failure 18 days after
hospitalization.

Discussion: Nivolumab recently received US Food and Drug Administration approval for every 4-week dosing based on pharmacokinetic data. Without clinical evidence, it was concluded that this increased dosing would not differ in safety or efficacy from previously approved doses, despite steady-state peak and average time concentrations predicted to be higher than the every 2-week dosing regimen. Both the National Comprehensive Cancer Network and American Society of Clinical Oncology recommend initiation of MMF for steroid refractory irAE transaminitis. These recommendations are based on case reports in patients receiving ipilimumab or nivolumab. The specific dosing and timing of initiation is not well elucidated. Additionally, there are case reports of use of antithymocyte globulin for management of irAEs.

Conclusions: Administration of 480-mg nivolumab may lead to more rapid onset of severe transaminitis. Administration of this dosing should be delayed until a patient demonstrates tolerability to the 240-mg dosing. High-dose steroids, in combination with MMF may provide more rapid clinical improvement. All patients on increased doses of immunosuppressive agents should receive opportunistic infection prophylaxis.

Purpose: To determine the efficacy and toxicity of fluorouracil/leucovorin/oxaliplatin (FOLFOX) vs capecitabine/oxaliplatin (XELOX or CAPOX) in the treatment of colorectal cancer (CRC) in both the adjuvant (aCRC) and metastatic (mCRC) setting in Veterans at the Southern Arizona Veteran Affairs Health Care System (SAVAHCS).

Methods: A retrospective chart review was conducted to collect efficacy and toxicity data. Subjects were included based on age, treatment setting, and regimen in the preset 5-year period, and appropriate diagnosis via International Classification of Diseases-Revision 9 (ICD-9) codes. Efficacy was measured via 1-year disease-free survival (DFS) for aCRC, progression-free survival (PFS) for mCRC, and overall survival (OS) for both settings.

Results: A total of 79 subjects were initially evaluatedwith 51 and 54 all-male subjects included in the efficacy and toxicity analysis, respectively. Mean range of age was 63-72 years old. Subjects were divided into four groups: FOLFOX aCRC (N = 17) and mCRC (N = 19), XELOX aCRC (N = 10) and mCRC (N = 8). No difference was found in 1-year DFS and OS between aCRC treatment groups, and PFS between mCRC groups. A higher incidence of 1-year OS with FOLFOX in the mCRC setting was noted (P = .03). No difference was found in the incidence of most of the toxicities between FOLFOX and XELOX, except a higher incidence of hand-foot syndrome was seen in XELOX (P = .0007) treated patients.

Conclusions: In this patient population, the efficacy between FOLFOX and XELOX in aCRC and mCRC was similar, while toxicity was slightly more prevalent with XELOX treatment due to increased hand-foot syndrome incidence. These findings are consistent with the results reported by previous larger prospective clinical trials.

Purpose: To determine the efficacy and toxicity of fluorouracil/leucovorin/oxaliplatin (FOLFOX) vs capecitabine/oxaliplatin (XELOX or CAPOX) in the treatment of colorectal cancer (CRC) in both the adjuvant (aCRC) and metastatic (mCRC) setting in Veterans at the Southern Arizona Veteran Affairs Health Care System (SAVAHCS).

Methods: A retrospective chart review was conducted to collect efficacy and toxicity data. Subjects were included based on age, treatment setting, and regimen in the preset 5-year period, and appropriate diagnosis via International Classification of Diseases-Revision 9 (ICD-9) codes. Efficacy was measured via 1-year disease-free survival (DFS) for aCRC, progression-free survival (PFS) for mCRC, and overall survival (OS) for both settings.

Results: A total of 79 subjects were initially evaluatedwith 51 and 54 all-male subjects included in the efficacy and toxicity analysis, respectively. Mean range of age was 63-72 years old. Subjects were divided into four groups: FOLFOX aCRC (N = 17) and mCRC (N = 19), XELOX aCRC (N = 10) and mCRC (N = 8). No difference was found in 1-year DFS and OS between aCRC treatment groups, and PFS between mCRC groups. A higher incidence of 1-year OS with FOLFOX in the mCRC setting was noted (P = .03). No difference was found in the incidence of most of the toxicities between FOLFOX and XELOX, except a higher incidence of hand-foot syndrome was seen in XELOX (P = .0007) treated patients.

Conclusions: In this patient population, the efficacy between FOLFOX and XELOX in aCRC and mCRC was similar, while toxicity was slightly more prevalent with XELOX treatment due to increased hand-foot syndrome incidence. These findings are consistent with the results reported by previous larger prospective clinical trials.

Purpose: To determine the efficacy and toxicity of fluorouracil/leucovorin/oxaliplatin (FOLFOX) vs capecitabine/oxaliplatin (XELOX or CAPOX) in the treatment of colorectal cancer (CRC) in both the adjuvant (aCRC) and metastatic (mCRC) setting in Veterans at the Southern Arizona Veteran Affairs Health Care System (SAVAHCS).

Methods: A retrospective chart review was conducted to collect efficacy and toxicity data. Subjects were included based on age, treatment setting, and regimen in the preset 5-year period, and appropriate diagnosis via International Classification of Diseases-Revision 9 (ICD-9) codes. Efficacy was measured via 1-year disease-free survival (DFS) for aCRC, progression-free survival (PFS) for mCRC, and overall survival (OS) for both settings.

Results: A total of 79 subjects were initially evaluatedwith 51 and 54 all-male subjects included in the efficacy and toxicity analysis, respectively. Mean range of age was 63-72 years old. Subjects were divided into four groups: FOLFOX aCRC (N = 17) and mCRC (N = 19), XELOX aCRC (N = 10) and mCRC (N = 8). No difference was found in 1-year DFS and OS between aCRC treatment groups, and PFS between mCRC groups. A higher incidence of 1-year OS with FOLFOX in the mCRC setting was noted (P = .03). No difference was found in the incidence of most of the toxicities between FOLFOX and XELOX, except a higher incidence of hand-foot syndrome was seen in XELOX (P = .0007) treated patients.

Conclusions: In this patient population, the efficacy between FOLFOX and XELOX in aCRC and mCRC was similar, while toxicity was slightly more prevalent with XELOX treatment due to increased hand-foot syndrome incidence. These findings are consistent with the results reported by previous larger prospective clinical trials.