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.

An exploratory study of body composition as a predictor of dose-limiting toxicity in metastatic pancreatic cancer treated with gemcitabine plus nab-paclitaxel.

BACKGROUND: Body composition is increasingly being studied as a method of predicting chemotherapy toxicity. Our study aimed to evaluate associations of body composition with treatment toxicity in a group of pancreatic cancer patients treated with gemcitabine plus nab-paclitaxel. METHODS: A retrospective review was performed for all patients who received first-line gemcitabine plus nab-paclitaxel for metastatic pancreatic cancer at a northern Alberta cancer institute (Canada) from 2014 to 2017. Total lean body mass (LBM) was derived from measurements of muscle surface area at L3 on baseline computed tomography (CT) scans. Optimal stratification, or minimal p-value analysis, was used to assess for a threshold of nab-paclitaxel dose per LBM (mg/kg) associated with a higher risk of dose-limiting toxicity (DLT). RESULTS: 152 patients were included in the study, of whom 62 (40.8%) experienced DLT. nab-Paclitaxel dose/LBM ranged from 0.98 to 8.76 mg/kg. A threshold for nab-paclitaxel dose/LBM that optimally predicted risk of DLT was identified at 5.83 mg/kg. Above this cut-off, 18/31 (58.1%) patients experienced DLT, compared to 44/121 (36.4%) patients below (p = 0.028). Patients above this cut-off had a higher incidence of peripheral neuropathy compared to those below, though this was not statistically significant based on an adjusted p-value threshold (48.4 vs. 29.8% respectively, p = 0.050). Body mass index, body surface area, and absolute initial doses of nab-paclitaxel or gemcitabine did not significantly impact likelihood of DLT. CONCLUSIONS: nab-Paclitaxel dose normalized to LBM, based on CT-derived measures of skeletal muscle, has potential to predict risk of chemotherapy toxicity. Chemotherapy dosing based on body composition, rather than conventional anthropometric measures, may be effective in reducing treatment toxicity.

Symptom burden among Northern Alberta radiotherapy patients with advanced cancer: mapping needs and gaps.

INTRODUCTION: Patients with advanced cancer often experience symptoms including pain, nausea, anorexia, fatigue, and depression. High symptom burden can be alleviated by multidisciplinary palliative care (PC) teams practicing symptom-directed management. Patients who are unable to access such services may be at higher risk of increased symptoms and poor outcomes. METHODS: A sequential exploratory mixed methods study was performed to explore the burden of symptoms experienced by Northern Alberta patients with advanced cancer. The symptom burden among patients from rural and remote communities was characterized in a retrospective review capturing basic demographic and clinicopathologic information, in addition to patient-reported outcomes. Symptom prevalence was evaluated against the nature and range of supportive care services available. Service accessibility was assessed at community level by surveying health care providers (HCPs) and performing thematic analysis on their responses. RESULTS: From January 1 to December 31, 2017, 607 outpatients were seen in consultation in an integrated palliative radiotherapy clinic in Edmonton, Alberta. A total of 166 (27.3%) patients resided in Alberta communities designated as rural or remote. Patient-reported symptom prevalence and intensity of scores did not differ significantly between rural/remote and urban populations. Unmet practical needs were flagged significantly more often by patients from rural communities (p = 0.05). HCPs from rural community health centers in Northern Alberta were knowledgeable regarding PC services availability and referral processes within their communities. CONCLUSION: Although the symptom burden experienced by patients living with advanced cancer in rural and remote areas of Northern Alberta does not differ significantly from their urban counterparts, and community HCPs are knowledgeable regarding PC services, unmet needs within these communities remain. Continuing support for PC services in rural communities, as well as establishing care pathways for patients from rural populations traveling to urban centers to receive treatment, will help to minimize the unmet needs these patients experience.

Effects of Proton Pump Inhibitors on FOLFOX and CapeOx Regimens in Colorectal Cancer.

BACKGROUND: First-line adjuvant chemotherapy options for early-stage colorectal cancer (CRC) include CapeOx (capecitabine, intravenous oxaliplatin) and FOLFOX (intravenous 5-fluorouracil, leucovorin, oxaliplatin). Capecitabine is an oral prodrug analog of 5-fluorouracil, and recent studies have suggested that proton pump inhibitors (PPIs) may detrimentally affect capecitabine efficacy. Conversely, some literature suggests that PPIs may negatively affect CRC itself. To gain insight into the nature of PPIs' effect on capecitabine and CRC, we investigated their effects on effectiveness of CapeOx versus FOLFOX chemotherapy. PATIENTS AND METHODS: We conducted a retrospective chart review of 389 patients with stage II-III CRC who received adjuvant CapeOx or FOLFOX from 2004 to 2013. Information regarding PPI receipt, chemotherapy, and patient outcomes from medical records was analyzed. RESULTS: Three-year recurrence-free survival was significantly lower in CapeOx-treated PPI recipients than non-PPI recipients (69.5 vs. 82.6%; P = .029). Unadjusted analysis showed that CapeOx-treated PPI recipients were twice as likely to experience cancer recurrence or death as CapeOx-treated non-PPI recipients (hazard ratio = 2.03; 95% confidence interval, 1.06-3.88; P = .033). FOLFOX-treated PPI recipients had a non-statistically significant difference in 3-year recurrence-free survival versus non-PPI recipients (82.9 vs. 61.7%; P = .066) and a non-statistically significant difference in recurrence/death (hazard ratio = 0.51; 95% confidence interval, 0.25-1.06; P = .071). No significant differences were seen in overall survival between groups. CONCLUSION: Our results suggest PPIs negatively affected recurrence-free survival in CapeOx-treated CRC patients and yielded no significant effects among FOLFOX-treated patients, potentially implicating a pharmacokinetic interaction between PPIs and capecitabine. No overall survival effects were seen. Given PPIs' widespread use, further studies are required to corroborate our findings.

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.

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.

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.