Rigor prophylaxis in stage IV melanoma and renal cell carcinoma patients treated with high dose IL-2.

BACKGROUND: Rigors are a significant adverse event during interleukin-2 (IL2) therapy for metastatic melanoma and renal cell carcinoma. Meperidine has been a mainstay for rigor prophylaxis but there is a paucity of data regarding possible alternatives. METHODS: Ninety one patients receiving IL2 therapy for metastatic renal cell carcinoma and melanoma at Huntsman Cancer institute (HCI), Utah from May 2009 to October 2016 were retrospectively evaluated for rigor prophylaxis. Forty two patients received meperidine and 49 received tramadol. Rigors were tabulated using the proxy of number of doses of as needed (PRN) rigor medications and normalized by IL2 doses. Other outcomes of fever, hypotension, and renal insufficiency were noted on a binary scale and normalized by cycles. Statistical analysis was performed utilizing univariate and multivariate negative binomial models. RESULTS: Ninety one patients were identified with metastatic melanoma or RCC who received high dose IL2 therapy. Forty two received meperidine and 49 received tramadol prophylaxis for rigors. Univariate negative binomial analysis shows incidence rate ratios (IRR): fever 0.41 (95% CI 0.28-0.62, p-value < 0.001), hypotension 1.7 (95% CI 1.11-2.61, p-value 0.015), renal insufficiency 0.58 (95% CI 0.35-0.98, p-value 0.041), rigors per all PRN meds 1.01 (95% CI 0.79-1.28, p-value 0.964), and rigors via opioid PRN meds 0.85 (95% CI 0.67-1.07, p-value 0.168). Multivariate negative binomial analysis shows IRR: fever 0.59 (95% CI 0.28-1.24, p-value 0.163), hypotension 0.93 (95% CI 0.43-2.03, p-value 0.864), renal insufficiency 1.1 (95% CI 0.52-2.32, p-value 0.807), rigors per al PRN meds 0.92 (95% CI 0.67-1.26, p-value 0.604), and rigors via opioid PRN 0.9 (95% CI 0.65-1.26, p-value 0.554). CONCLUSION: Univariate models indicated meperidine pre-treatment was associated with significantly lower rates of fever and renal insufficiency whereas tramadol was associated with significantly lower rate of hypotension. However, when controlled for demographics and other treatment differences, these differences were no longer significant.

Phenytoin and Rifampin Do Not Decrease Levels in Acute Tacrolimus Toxicity.

Tacrolimus is used in bone marrow transplant patients to prevent graft-versus-host disease. There have been few case reports of tacrolimus toxicity (>30 ng/mL) in solid organ recipients as well as in nontransplant patients. Several case reports suggest phenytoin and rifampin decrease tacrolimus levels in toxicity, but does it actually make a difference? A 60-year-old man with acute myeloblastic leukemia after allogenic stem cell transplant with fever, diarrhea, and abdominal pain was transferred to the intensive care unit for persistent hypotension and acute hypoxic respiratory failure requiring intubation. The following day his tacrolimus level was 8.6 ng/mL and creatinine was 2.2 (baseline = 1.8). The patient inadvertently received 15 mg intravenous tacrolimus instead of his scheduled 0.5 mg intravenous. Four hours later, a random tacrolimus level was 36.4 ng/mL. Tacrolimus was discontinued; phenytoin 200 mg BID was started for 4 doses and rifampin was started for 2 doses at 600 mg. Sixteen hours postinjection, tacrolimus level decreased to 26.4 ng/mL and to 9 ng/mL after 64 hours. Creatinine improved to 1.1 after 30 hours. He was extubated 5 days later without any new neurological findings and his creatinine returned to baseline. Our patient received 30 times his daily dose resulting high tacrolimus levels. Assuming there was sufficient time for distribution, our patient's half-life increased to 34.5 hours compared with the reported half-life of 12 hours. The possibilities for this increase include ineffective or harmful effects of the phenytoin/rifampin combination, change in metabolism kinetics at high levels, or other unidentified patient-specific factors. Further studies should be done to ensure that phenytoin and rifampin are safe to give in tacrolimus toxicity.

Neutrophil-to-lymphocyte Ratio (NLR) as a predictor for recurrence in patients with stage III melanoma.

Neutrophil-to-lymphocyte ratio is a strong predictor for overall survival and disease free survival in many cancers. Our study is the first investigation aiming to determine the predictive value of neutrophil-to-lymphocyte ratio on prognosis of patients with stage III melanoma. This retrospective study utilized a cohort of 107 patients with stage III melanoma treated at Huntsman Cancer Institute, University of Utah, from May 2002 to March 2016. The optimal cutoff of neutrophil-to-lymphocyte ratio was determined by the significance of log-rank tests. A total of 97 log-rank tests were conducted to find the optimal cutoff. Disease free survival was assessed using the Kaplan-Meier method, and univariable and multivariable Cox models were applied to evaluate the predictive value of neutrophil-to-lymphocyte ratio. 2.5 was identified as the optimal cutoff. Kaplan-Meier curve showed that the disease free survival rate of the low value group was significantly higher compared to that of high value group. After adjusting for confounders and other prognostic factors, the neutrophil-to-lymphocyte ratio ≥ 2.5 remained a strong predictor for disease recurrence in patients with stage III melanoma.

Narcoleptic-like Episodes in a Patient Receiving Pegylated Interferon-alpha 2b: A Case Report and Review of Literature.

A 26-year-old male developed narcoleptic-like episodes while on pegylated interferon-alpha 2b (peg-IFN-α2b) therapy for stage IIIB melanoma. Once peg-IFN-α2b was discontinued, the narcoleptic-like episodes eradicated. A case report and review of the literature are presented in this article.