Use of nab-paclitaxel and gemcitabine in pancreatic cancer without granulocyte colony-stimulating factor: A multicenter real-world experience.

INTRODUCTION: The metastatic pancreatic adenocarcinoma clinical trial (MPACT) trial established gemcitabine (gem) and nab-paclitaxel (nab) as a standard treatment for pancreatic cancer utilizing granulocyte colony-stimulating factors to manage neutropenia. This was a challenge for jurisdictions that do not use granulocyte colony-stimulating factors in palliative settings. We developed dosage guidelines to dose modify gem and nab without granulocyte colony-stimulating factors. We undertook a retrospective review to determine the efficacy and safety of these dose adjustment guidelines in the real world. METHODS: A multi-centered, retrospective chart review was performed on pancreatic patients between December 1, 2014, and August 21, 2018. Provincial electronic medical health records were reviewed. Using Log-rank statistics we determined the patient's progression-free survival and overall survival. RESULTS: Of 248 patients, 209 met patient selection criteria. Patients were excluded if they were lost to follow-up, on gem alone prior to nab/gem combination therapy or did not receive nab or gem. Patients who received nab/gem as first-line therapy had a median progression-free survival of 6.3 months (95% CI, 5.1-7.4), and median overall survival of 11.1 months (95% CI, 9.5-12.8). Those who received gem/nab in the second line had a median progression-free survival of 4.6 months (95% CI, 2.8-6.5), and median overall survival of 19.3 months (95% CI, 12.6-26.0). CONCLUSIONS: The patient's progression-free survival and overall survival taking nab/gem using our dose modification algorithm were equivalent or superior to the MPACT trial's progression-free survival and overall survival. Gem/nab can be given by our dose modification scheme without granulocyte colony-stimulating factor.

Incidence of late onset neutropenia associated with rituximab use in B cell lymphoma patients undergoing autologous stem cell transplantation.

Reversible late onset neutropenia associated with rituximab has been reported with incidence rates varying from 15 to 70% in B cell lymphoma patients receiving autologous stem cell transplantation. We conducted a retrospective descriptive study at one tertiary care center in adult B cell lymphoma patients treated with rituximab and autologous stem cell transplantation between 1 January 2004 and 30 June 2014. Late onset neutropenia was defined as an absolute neutrophil count <1.0 × 109 cells/L after neutrophil engraftment and less than six months post autologous stem cell transplantation. The primary objective was to determine the incidence of late onset neutropenia. The secondary objectives were to examine whether the use of rituximab with re-induction therapy, mobilization or high dose chemotherapy regimens increased the risk for late onset neutropenia, and to evaluate infectious complications. Of 315 subjects, 92 (29.2%) developed late onset neutropenia. Mobilization regimens containing rituximab (OR 2.90 95% CI: 1.31-6.40), high dose chemotherapy containing rituximab (OR 1.87 95% CI: 1.14-3.05), and exposure to rituximab in either or both regimens (OR 3.05 95% CI: 1.36-6.88) significantly increased the risk of late onset neutropenia. While neutropenic, 17.4% experienced an infection, 7.6% experienced febrile neutropenia, and 5.4% were hospitalized. In conclusion, rituximab with mobilization or high dose chemotherapy may increase the risk of late onset neutropenia post autologous stem cell transplantation.

Does gastric acid suppression affect sunitinib efficacy in patients with advanced or metastatic renal cell cancer?

INTRODUCTION: Renal cell cancer is a chemotherapy-insensitive cancer treated by vascular endothelial growth factor receptor antagonists. Recently, a question has arisen on whether there is an interaction between tyrosine kinase inhibitors, such as sunitinib, and acid suppressing agents. METHODS: A retrospective chart review was conducted for patients at two tertiary care centers who received sunitinib between 1 January 2006 and 31 March 2013. Using electronic systems and a province-wide electronic health records database, medication dispensing records were obtained. A univariate Cox's proportional hazard model determined if acid suppression had effects on progression-free survival and overall survival. RESULTS: Of 383 patient charts reviewed, 231 were included in the study. Patients on intermittent acid suppression, lost to follow-up or received sunitinib for less than one week were excluded from the study. The median age of the study population was 65. Patients who received no acid suppression (n = 186) had a median progression-free survival of 23.6 weeks (95% CI, 19.0-31.9 weeks) and patients who received continuous acid suppression (n = 45) had a median progression-free survival of 18.9 weeks (95% CI, 11.0-23.7 p = 0.04). A median overall survival of 62.4 weeks (95% CI, 42.0-82.7 weeks) was observed in the group with no acid suppression, while a median overall survival of 40.9 weeks (95% CI, 26.1-74.4 weeks) was observed in the continuous acid suppression group (p = 0.02). CONCLUSION: There was a significant difference in progression-free survival and overall survival between the acid suppressed and no acid suppression groups. Further research is required to confirm this potential interaction.

Oncology Drug Dosing in Gilbert Syndrome Associated with UGT1A1: A Summary of the Literature.

Gilbert syndrome (GS) is a hereditary condition that affects ~10% of the population. It is characterized by intermittent, unconjugated hyperbilirubinemia in the absence of hepatocellular damage and hemolysis. Although GS is often described as a benign laboratory finding, it may alter drug metabolism by decreasing the ability to conjugate drugs. Genetic polymorphisms, specifically the UGT1A1*28 allele, may reduce glucuronidation by 30% that severely impacts the ability to metabolize certain medications. Antineoplastic agents used in oncologic settings have toxic side effects, and alterations in metabolism may result in severe or even life-threatening toxicities. Many of the drug monographs provided by manufacturers contain dose adjustment parameters for hepatic function, using serum bilirubin as a surrogate marker. However, in patients with GS, hepatic function remains normal in the setting of hyperbilirubinemia, and scant literature is available to provide guidance on empirical dosage adjustment. In this review, we conducted a literature search of routinely used oncology medications and assessed the need for empirical dose adjustments in the setting of GS.