NCCN Guidelines® Insights: Hematopoietic Growth Factors, Version 1.2022.

The NCCN Guidelines for Hematopoietic Growth Factors provide recommendations for the appropriate use of growth factors in the clinical management of febrile neutropenia (FN), chemotherapy-induced thrombocytopenia (CIT), and chemotherapy-induced anemia (CIA). Management and prevention of these sequelae are an integral part of supportive care for many patients undergoing cancer treatment. The purpose of these guidelines is to operationalize the evaluation, prevention, and treatment of FN, CIT, and CIA in adult patients with nonmyeloid malignancies and to enable the patient and clinician to assess management options for FN, CIT, and CIA in the context of an individual patient's condition. These NCCN Guidelines Insights provide a summary of the important recent updates to the NCCN Guidelines for Hematopoietic Growth Factors, with particular emphasis on the incorporation of a newly developed section on CIT.

Xerostomia: an immunotherapy-related adverse effect in cancer patients.

PURPOSE: Xerostomia is an underrecognized adverse effect of immunotherapy (IO) that can significantly impact patients' quality of life by leading to poor nutritional status, dental caries, and oral candidiasis. The purpose of this case series was to describe the onset, severity, clinical course, and management of IO-induced xerostomia. METHODS: This was a retrospective case series conducted at an outpatient cancer center. Data collection was conducted via chart review. The severity of dry mouth symptoms was graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: Six patients with advanced solid tumors who received a PD-1 inhibitor or PD-1/CTLA-4 inhibitor combination therapy were evaluated. The median time to onset of xerostomia was 4.5 months overall, though symptoms developed sooner in patients who received IO as subsequent-line therapy (median = 1.9 months). All patients developed other immune-related adverse events (IRAEs) such as hypothyroidism. Five patients (83%) had grade 2 dry mouth symptoms, and similarly, 5 patients eventually required prescription medications such as sialogogues and topical or systemic corticosteroids to alleviate symptoms. Two patients (33%) required interruptions in IO. All 3 patients who received cevimeline noticed improvement in symptoms, and one patient who received prednisone dosed at 1 mg/kg/day tapered over 5 weeks also experienced significant relief. CONCLUSION: While the optimal management of IO-induced xerostomia has not yet been established by national guidelines, increased awareness can prompt faster initiation of supportive care measures that can prevent significant discomfort and poor oral intake. Thoughtful use of over-the-counter topical agents, sialogogues, corticosteroids, and treatment interruptions can help improve tolerability of this adverse effect.

Considerations for Use of Hematopoietic Growth Factors in Patients With Cancer Related to the COVID-19 Pandemic.

Hematopoietic growth factors, including erythrocyte stimulating agents (ESAs), granulocyte colony-stimulating factors, and thrombopoietin mimetics, can mitigate anemia, neutropenia, and thrombocytopenia resulting from chemotherapy for the treatment of cancer. In the context of pandemic SARS-CoV-2 infection, patients with cancer have been identified as a group at high risk of morbidity and mortality from this infection. Our subcommittee of the NCCN Hematopoietic Growth Factors Panel convened a voluntary group to review the potential value of expanded use of such growth factors in the current high-risk environment. Although recommendations are available on the NCCN website in the COVID-19 Resources Section (https://www.nccn.org/covid-19/), these suggestions are provided without substantial context or reference. Herein we review the rationale and data underlying the suggested alterations to the use of hematopoietic growth factors for patients with cancer in the COVID-19 era.

NCCN Guidelines Insights: Hematopoietic Growth Factors, Version 1.2020.

Management of febrile neutropenia (FN) is an integral part of supportive care for patients undergoing cancer treatment. The NCCN Guidelines for Hematopoietic Growth Factors provide suggestions for appropriate evaluation, risk determination, prophylaxis, and management of FN. These NCCN Guidelines are intended to guide clinicians in the appropriate use of growth factors for select patients undergoing treatment of nonmyeloid malignancies. These NCCN Guidelines Insights highlight important updates to the NCCN Guidelines regarding the incorporation of newly FDA-approved granulocyte-colony stimulating factor biosimilars for the prevention and treatment of FN.

Establishing clinical pharmacist telehealth services during the COVID-19 pandemic.

PURPOSE: After community transmission of the novel virus that causes coronavirus disease 2019 (COVID-19) was detected in the State of Washington in February 2020, innovative measures, such as telehealth appointments, were needed to safely continue to provide optimal pharmaceutical care for patients with chronic conditions and cancer. SUMMARY: Prior to the COVID-19 pandemic, federal regulations limited the scope of telehealth pharmacist services. However, enactment of the Coronavirus Preparedness and Response Supplemental Appropriations Act, followed by guidance by the Centers for Medicare and Medicaid Services and the Department of Health and Human Services, allowed currently credentialed providers (including pharmacists) to continue to provide patient care services via telehealth with fewer restrictions. Our health system has numerous credentialed pharmacists across multiple ambulatory care clinics. In this article, we highlight our process of expediting the implementation of telehealth services. This process included obtaining authorization for the credentialed pharmacists to provide telehealth services, completion of training modules, implementation of new technology platforms, development of new workflows, and utilization of resources for providers and patients to facilitate successful completion of telehealth visits. We also highlight the consent and documentation components crucially important to the telehealth visit and share some of our successes, as well as identified limitations, in providing pharmacist services via telehealth. CONCLUSION: In the setting of the COVID-19 pandemic, our institution was able to swiftly implement clinical pharmacist telehealth services for many patients, offering a safe and effective way to continue providing a high level of care. This article discusses our experience with and potential limitations of telehealth to assist other pharmacists seeking to implement and/or expand their telehealth services.

Expanding pharmacy practice through the use of pharmacy technicians as process navigators to facilitate patient access of oral anticancer agents.

OBJECTIVES: Over the past 20 years, there has been an increase in the number of Food and Drug Administration-approved oral anticancer agents. Treatment with the use of these medications can offer patients many benefits, including increased convenience and improved quality of life. However, oral anticancer therapies are associated with significant challenges, including cost and difficulties in obtaining the medication. SETTING: Oncology pharmacists and nurses at the Seattle Cancer Care Alliance oversaw the entire process of oral anticancer therapies, from obtaining signatures and insurance authorization to completing patient education and sending the prescription to the preferred pharmacy. This often led to duplicative efforts and challenges with communication amongst all the team members. PRACTICE DESCRIPTION: The pharmacy department piloted a trained pharmacy technician who was provided the role of process navigator to facilitate and coordinate the entire insurance authorization and patient assistance process involved in obtaining access to oral anticancer medications. Before implementation of the program, the average time spent in total for each oral anticancer prescription was 45.8 minutes for the clinic nurses, 21.8 minutes for the clinical pharmacists, and 45.8 minutes for the pharmacy billing technicians. There was an 89.7% success rate in obtaining these medications for patients. RESULTS: After implementation of this program, the pharmacy technician serving as the process navigator significantly improved efficiency and required an average of 59.5 minutes to complete the same steps, compared with 114 minutes before implementation. After program implementation, it was also observed that the pharmacist and nurse were spending much less time on the insurance authorization process. After implementation of this new role, the success rate of obtaining oral anticancer medications increased to 93.1%. CONCLUSION: This innovative initiative expanded the scope of practice for pharmacy technicians and enabled the other team members to spend time on more clinical activities.

Hepatitis C infection and chemotherapy toxicity.

There exists little guidance on chemotherapy toxicity management in patients with a history of or active hepatitis C viral infection. We report four cases of patients with solid organ tumors and hepatitis C viral infection, who have experienced severe or unexpected toxicities with chemotherapy. Based on the four case reports, we recommend increased laboratory monitoring for toxicities, initial dose reductions for chemotherapy given with palliative intent, or pre-emptive use of growth factor support, even if the patient presents with normal liver function tests. In this patient population, we also recommend treating active hepatitis C viral infection prior to chemotherapy treatment when possible.

Renal toxicity with liposomal doxorubicin in metastatic breast cancer.

There is no preferred treatment option for metastatic breast cancer; therefore, treatment should provide palliation, prolong survival, control symptoms, and improve quality of life. Liposomal doxorubicin formulations have been shown to have less alopecia, nausea, vomiting, and myelosuppression than traditional doxorubicin, but more skin toxicities and infusion reactions. Prolonged use of liposomal doxorubicin may be associated with unrecognized or less well-defined toxicities. We report a case of acute kidney injury and progressively worsening chronic kidney disease necessitating dialysis in a patient who received prolonged therapy with liposomal doxorubicin for treatment of metastatic breast cancer. This case report should give caution to providers considering prolonged use of liposomal doxorubicin in the metastatic breast cancer setting as we observed sustained renal toxicity, long past the cessation of treatment.

Collaborative practice model for management of pain in patients with cancer.

PURPOSE: The use of a collaborative drug therapy agreement (CDTA) by oncology pharmacists in a comprehensive pain clinic is described. SUMMARY: Recognizing the complex clinical services required by patients with cancer, the Seattle Cancer Care Alliance began offering cancer pain management through a specialized pain service. Initially, the clinic was staffed by one attending physician; however, as the volume of patient referrals increased, the clinic expanded into an interprofessional team that includes physicians, advanced practice providers, nurses, and pharmacists. Through an extensive credentialing process and under the guidance of a CDTA, pharmacists in the pain clinic are able to evaluate patients, develop treatment plans, and prescribe pain medication therapies for oncology patients. By having pharmacists provide these services, the pain clinic can improve medication dosing, ensure that medications are managed consistently, improve patients' quality of care, and save providers time by allowing tasks to be completed by appropriately trained ancillary staff. For cancer-related pain, the pharmacist, in conjunction with the attending provider, develops a pain medication plan following the principles of the World Health Organization's analgesic ladder. The pain clinic has implemented the routine use of several validated tools for screening and assessment of opioid risk as well as state guidelines for managing chronic opioid therapy. The pharmacists in the pain clinic also emphasize functional goals and improvement in functional status rather than complete relief of pain. CONCLUSION: As members of an interprofessional pain clinic team, oncology pharmacists use their specialized knowledge of cancer and pharmacotherapy to help manage and treat pain in complex cancer cases.

Routine proteinuria monitoring for bevacizumab in patients with gynecologic malignancies.

BACKGROUND: Proteinuria leading to nephrotic syndrome is a rare adverse event arising from treatment with bevacizumab. There is limited evidence to guide the frequency and appropriate test for monitoring for proteinuria. The purpose of this study was to determine the prevalence and severity of proteinuria during bevacizumab administration to patients with gynecologic malignancies, and to evaluate risk factors associated with this toxicity; a secondary objective was to evaluate the cost of routine proteinuria monitoring to assess for opportunities of cost containment that could change clinical practice. METHODS: A retrospective chart review was performed at an academic gynecologic oncology clinic. Women over 18 years of age with a diagnosed gynecologic malignancy were evaluated for the development of proteinuria while receiving bevacizumab treatment as measured by a urine protein-to-creatinine ratio. Patient and disease-specific risk factors were evaluated using logistic regression to determine correlations of risk factors to development of proteinuria. Cost assessment was performed using institution-specific data for urine laboratory tests. RESULTS: Eighty-nine patients were identified, and the overall prevalence of proteinuria of any grade was 35%. The mean number of bevacizumab cycles was 13 (2-64 cycles). The majority of patients experienced grade 1 proteinuria (70%, 62 patients). Grade 3 proteinuria was observed in two patients (2%). There was a trend toward increased bevacizumab cycles associated with increased grade proteinuria (p = 0.053), however there were no factors significantly associated with the development of proteinuria as measured by urine protein-to-creatinine ratio. CONCLUSION: Monitoring of urine protein-to-creatinine ratios with each cycle may be unnecessary due to the low prevalence of grade 3 proteinuria observed. Additionally, urine protein-to-creatinine ratios may not provide adequate assessment of proteinuria toxicity associated with bevacizumab therapy. Potential cost savings opportunities for the institution can be realized with a cost-reductive monitoring algorithm that will utilize less costly laboratory techniques for patients at high risk of developing proteinuria.

Comparison of acute toxicity and mortality after two different dosing regimens of high-dose interleukin-2 for patients with metastatic melanoma.

We compared acute toxicity, drug exposure, in-hospital mortality, and inpatient length of stay between two currently recommended dosing protocols (from the National Comprehensive Cancer Network Guidelines) of high-dose interleukin-2 (IL-2) treatment for patients with metastatic melanoma. Patients with metastatic melanoma who received high-dose IL-2 treatment between 2003 and 2010 were identified. Chemotherapy orders, electronic medical records, paper medical charts, and patient discharge summaries were reviewed retrospectively. We identified 13 patients who had received 600,000 units/kilogram (kg)/dose and 15 patients who had received 720,000 units/kg/dose. Patients in the 720,000 units/kg/dose group had a higher rate of grade 3 and 4 bilirubin elevations (34 vs. 12 %), weight gain (any grade, 96 vs. 89 %), and thrombocytopenia (any grade, 75 vs. 65 %). Patients receiving the higher dose also experienced more dose-limiting neurotoxicity (45 vs. 23 %), large-volume diarrhea (15 vs. 0 %), and hepatotoxicity (7 vs. 0 %). There was no in-hospital mortality during treatment in either group. The average length of stay was similar between both groups (5 days, SD = 1 for both groups), and the median cumulative IL-2 exposure was similar between both groups for the first course (10.1 vs.10.5 million units/kg) and for all courses (approximately 11-12 million units/kg). Both high-dose IL-2 protocols had comparable in-hospital mortality and cumulative IL-2 exposure. The 720,000 units/kg/dose dosing scheme did not shorten the length of stay but did lead to greater acute toxicity. Therefore, as a result, we recommend 600,000 units/kg/dose when deciding between the two regimens.

Recurrence patterns after extended treatment with bevacizumab for ovarian, fallopian tube, and primary peritoneal cancers.

OBJECTIVE: To evaluate patterns of recurrence for ovarian, fallopian tube, and primary peritoneal cancer patients undergoing extended treatment with bevacizumab (BEV). METHODS: A retrospective review of patients with primary ovarian, fallopian tube, or peritoneal cancer treated with BEV alone or in combination with other chemotherapy from 2001 to 2011 was performed. Qualified patients were identified by chemotherapy records. Electronic medical records, labs, and imaging reports were reviewed and abstracted. RESULTS: Of 108 patients identified, 89 patients met study criteria by having disease progression either during treatment with BEV or after discontinuing BEV without initiating any other treatment. Patients on extended BEV therapy (>12 cycles) were more likely to recur in extra-visceral sites (p=0.04), especially in lymph nodes (p=0.0002), and presented with fewer symptoms at time of recurrence (p=0.02), compared to patients who had received ≤ 12 cycles. CA-125 becomes less reliable for the detection of recurrent disease with extended BEV therapy (p=0.03 for ≤12 cycles vs. p=0.08 for >12 cycles). Radiology was superior to CA-125, symptom, and physical exam, in detecting recurrence with extended BEV therapy (all p<0.0001). CONCLUSIONS: Extended treatment with BEV in ovarian, fallopian tube, and peritoneal cancers results in alterations in the patterns of recurrence. Radiologic imaging is more reliable than CA-125, symptoms, or physical exam, in identifying recurrent disease in patients undergoing BEV treatment. As novel targeted therapies continue to be employed, guidelines for gynecologic cancer surveillance must continue to be reexamined.