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.

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.

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.

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.

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.