A Guide to Implementing Immune Checkpoint Inhibitors within a Cancer Program: Experience from a Large Canadian Community Centre.

The increased use of immune checkpoint inhibitors across cancer programs has created the need for standardized patient assessment, education, monitoring, and management of immune-related adverse events (irAEs). At William Osler Health System in Brampton, Ontario, a practical step-wise approach detailing the implementation of cancer immunotherapy in routine practice was developed. The approach focuses on four key steps: (1) identification of patient educators; (2) development of patient education materials; (3) development of patient monitoring tools; (4) involvement and education of multidisciplinary teams. Here, we provide an in-depth description of what was included in each step and how we integrated the different elements of the program. For each step, resources, tools, and materials that may be useful for patients, healthcare providers, and multidisciplinary teams were developed or modified based on existing materials. At our centre, the program led to improved patient comprehension of irAEs, the ability to act on symptoms (patient self-efficacy), and low rates of emergency room visits at first presentation for irAEs. We recognize that centres may need to tailor the approaches to their institutional policies and encourage centres to adapt and modify the forms and tools according to their needs and requirements.

Remote, proactive, telephone based management of toxicity in outpatients during adjuvant or neoadjuvant chemotherapy for early stage breast cancer: pragmatic, cluster randomised trial.

OBJECTIVE: To evaluate the effectiveness of remote proactive management of toxicities during chemotherapy for early stage breast cancer. DESIGN: Pragmatic, cluster randomised trial. SETTING: 20 cancer centres in Ontario, Canada, allocated by covariate constrained randomisation to remote management of toxicities or routine care. PARTICIPANTS: All patients starting adjuvant or neoadjuvant chemotherapy for early stage breast cancer at each centre. 25 patients from each centre completed patient reported outcome questionnaires. INTERVENTIONS: Proactive, standardised, nurse led telephone management of common toxicities at two time points after each chemotherapy cycle. MAIN OUTCOME MEASURES: The primary outcome, cluster level mean number of visits to the emergency department or admissions to hospital per patient during the whole course of chemotherapy treatment, was evaluated with routinely available administrative healthcare data. Secondary patient reported outcomes included toxicity, self-efficacy, and quality of life. RESULTS: Baseline characteristics of participants were similar in the intervention (n=944) and control arms (n=1214); 22% were older than 65 years. Penetration (that is, the percentage of patients who received the intervention at each centre) was 50-86%. Mean number of visits to the emergency department or admissions to hospital per patient was 0.91 (standard deviation 0.28) in the intervention arm and 0.94 (0.40) in the control arm (P=0.94); 47% (1014 of 2158 patients) had at least one visit to the emergency department or a hospital admission during chemotherapy. Among 580 participants who completed the patient reported outcome questionnaires, at least one grade 3 toxicity was reported by 48% (134 of 278 patients) in the intervention arm and by 58% (163 of 283) in the control arm. No differences in self-efficacy, anxiety, or depression were found. Compared with baseline, the functional assessment of cancer therapy trial outcome index decreased by 6.1 and 9.0 points in the intervention and control participants, respectively. CONCLUSIONS: Proactive, telephone based management of toxicities during chemotherapy did not result in fewer visits to the emergency department or hospital admissions. With the rapid rise in remote care because of the covid-19 pandemic, identifying scalable strategies for remote management of patients during cancer treatment is particularly relevant. TRIAL REGISTRATION: ClinicalTrials.gov NCT02485678.

Granulocytic sarcoma in a patient with myelodysplastic syndrome.

Granulocytic sarcomas (GS) are uncommon extramedullary tumors composed of immature cells of the granulocytic or myeloid series. Treatment for GS should be directed toward the underlying hematologic disorder. There is no standard treatment.

Lepirudin in the management of heparin-induced thrombocytopenia.

BACKGROUND: Lepirudin is a recombinant hirudin that exerts its anticoagulant effect by direct inhibition of thrombin. Lepirudin is indicated for anticoagulation in patients with heparin-induced thrombocytopenia (HIT) and associated thromboembolic disease to prevent further thromboembolic complications. OBJECTIVE: This review addresses various clinical uses of lepirudin including but not limited to FDA approved indication. The objective is to provide an updated overview of the clinical use and pharmacology of the agent. In addition, we address certain areas of controversy especially pertaining to dosing of lepirudin and its use in different clinical situations. METHODS: Literature was reviewed using appropriate search terms in Pubmed and Ovid medline databases. RESULTS/CONCLUSION: Lepirudin continues to be a valuable anticoagulant in the management of HIT. Lepirudin has the highest recommendation in treatment of HIT based on evidence from clinical trials. Minor modifications in dosing over the standard label recommendations may simplify its use and enhance safety.

Prolonged half-life of argatroban in patients with renal dysfunction and antiphospholipid antibody syndrome being treated for heparin-induced thrombocytopenia.

Argatroban is a direct thrombin inhibitor approved for the treatment of heparin-induced thrombocytopenia (HIT) type II. Argatroban is predominantly metabolized in the liver. It is widely believed that no dosage adjustment is required in patients with renal insufficiency, making it a preferred agent in patients on renal replacement therapy (Reddy and Grossman, Ann Pharm 2005;39:1601-1605). The elimination half-life of argatroban is approximately 50 min. Lupus anticoagulants can cause baseline elevation of the PTT and hence it is difficult to monitor the effects of anticoagulants such as heparin, lepirudin, or argatroban in patients with antiphospholipid antibody syndrome. Heparin levels may be used as an alternative for heparin monitoring but plasma levels of argatroban are not commercially available. A chromogenic antifactor IIa assay could be useful for monitoring argatroban in the presence of a lupus anticoagulant, but it is not widely available at present. We report a patient with end-stage renal disease, maintained on peritoneal dialysis with HIT, who demonstrated a markedly prolonged half-life when treated with argatroban despite the discontinuation of therapy. This case also demonstrates the lack of guidelines for the monitoring of argatroban therapy in the presence of an underlying lupus anticoagulant.

An open-label study of tiagabine as augmentation therapy for anxiety.

BACKGROUND: At least 50% of patients with anxiety disorders experience only partial response to pharmacotherapy and require augmentation therapy. Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the CNS, and agents that modulate GABA neurotransmission have shown promise in the treatment of anxiety disorders and are often used as augmentation agents. OBJECTIVE: This study evaluated tiagabine, a selective GABA reuptake inhibitor (SGRI), as augmentation therapy. METHODS: This 8-week, open-label study enrolled patients who remained symptomatic despite adequate drug trials for treatment of anxiety symptoms. Tiagabine augmentation therapy was initiated at 4 mg/d (taken in 2 doses; one in the morning with breakfast and one in the evening with a snack) for 2 days and increased to 8 mg/d for 10 days. Dose was then adjusted according to efficacy/tolerability in increments of 2 mg every 3 days up to a maximum of 20 mg/d. Effect was assessed using the Hamilton Rating Scale for Anxiety (HAM-A), Beck Anxiety Inventory (BAI), Clinical Global Impression (CGI) scale, Pittsburgh Sleep Quality Index (PSQI), and 36-item Short-Form Health Survey (SF-36). RESULTS: Of the 18 patients enrolled, 17 were included in the efficacy analysis; one withdrew due to an adverse event prior to post-baseline assessment. Mean final dose of tiagabine was 13 mg/d. Tiagabine as augmentation therapy further reduced anxiety symptoms, as shown by significant decreases in mean HAM-A total and BAI scores at Week 8 (P<0.001). Thirteen patients (76%) responded (> or =50% reduction in HAM-A total score), and 10 patients (59%) achieved remission (HAM-A total score < or =7) at Week 8. Tiagabine improved sleep quality, with a significant reduction seen in PSQI global score at Week 8 (P=.001). Augmentation therapy with tiagabine was generally well tolerated. CONCLUSION: These preliminary findings suggest that the SGRI tiagabine may be an effective and generally well tolerated augmentation therapy in patients with anxiety who remain symptomatic despite adequate drug trials for treatment of anxiety symptoms.

An open-label study of adjunctive modafinil in patients with sedation related to serotonergic antidepressant therapy.

OBJECTIVE: In patients with major depressive disorder (MDD), excessive sleepiness and fatigue not only are major components of the disorder, but also may occur as side effects of antidepressant therapy. In addition, sedation may be a consequence of antidepressant regimens. The novel wake-promoting agent modafinil improves wakefulness and reduces fatigue across a variety of clinical disorders. This study assessed the use of modafinil as an adjunctive treatment in patients with MDD who reported sedation related to serotonergic antidepressant therapy. METHOD: Data were collected between September 2001 and December 2003. Twenty men and women with DSM-IV-defined MDD were enrolled in this 3-week, open-label, single-center study. In addition to ongoing and stable treatment with selective serotonin reuptake inhibitors (SSRIs), clinic patients received modafinil once daily. Efficacy assessments were conducted at 1-week intervals. RESULTS: Sixteen patients (80%) completed the study. Modafinil plus SSRIs significantly improved overall depressive symptoms, as shown by reductions in mean Hamilton Rating Scale for Depression total scores (p <.001 vs. baseline). Adjunctive modafinil significantly improved subjective estimates of wakefulness on the Epworth Sleepiness Scale (p <.001, all weeks) and reduced fatigue on the Fatigue Severity Scale (p =.009). At the final visit, modafinil had improved overall health status and health-related quality of life, as shown by significant improvements in mean Medical Outcomes Study Short-Form 12-Item Health Survey total scores (p =.007) and in physical health (p =.04) and mental health (p =.006) subscores. CONCLUSION: In patients with MDD who experience sedation as a side effect of antidepressant therapy, adjunctive modafinil improved wakefulness and reduced fatigue. Modafinil plus SSRIs also improved mood and quality of life.