Safety of temozolomide use in adult patients with renal dysfunction.

PURPOSE: Temozolomide (TMZ), a cytotoxic DNA alkylating agent, is the main chemotherapy used for the treatment of high grade astrocytomas. The active alkylator, methylhydrazine, is not recovered in urine and thus renal function is not expected to affect clearance. Prescribing information for TMZ states pharmacokinetics have not been studied in adults with poor renal function, eGFR < 36 mL/min/1.73 m2. We reviewed our clinical experience with TMZ in patients with impaired renal function to evaluate safety of administering full dose TMZ. METHODS: The primary endpoint was to characterize the incidence and severity of thrombocytopenia in patients with eGFR < 60 mL/min/1.73 m2 who received TMZ for treatment of high grade gliomas (HGG) or primary CNS lymphoma (PCNSL). Secondary endpoints included incidence and severity of neutropenia, lymphopenia hepatotoxicity, and number of TMZ cycles administered. Medical records of patients with HGG or PCNSL treated with TMZ from October 1, 2016-September 30, 2019 were accessed to identify cases for this study. RESULTS: Thirty-two patients were eligible for this study. Of the seven patients with eGFR < 36 mL/min/1.73m2, 38/39 cycles (97%) were completed without grade 3-4 thrombocytopenia. No patients experienced grade 3-4 neutropenia, and grade 3-4 lymphopenia occurred in 5 cycles (15%). One patient discontinued TMZ 7 days prior to completion of radiation due to thrombocytopenia. CONCLUSION: Hematologic toxicity in patients with severe renal dysfunction, eGFR < 36 mL/min/1.73m2, is similar to that of patients with normal renal function. Severe renal impairment does not preclude use of temozolomide, but cautious monitoring of blood counts is warranted.

Pertuzumab-associated diarrhea in HER2/neu-positive breast cancer patients: A comparison of trials to actual practice.

BACKGROUND: Although landmark trials in the metastatic (CLEOPATRA) and neo-adjuvant (NeoSphere; TRYPHAENA) settings identified all-grade diarrhea as a pertuzumab-associated adverse event, it was not classified as dose-limiting. In actual practice, diarrhea is often a reason for treatment modifications. OBJECTIVES: To compare the risk of pertuzumab-associated diarrhea in actual practice to the risks in randomized controlled trials. METHODS: We conducted a retrospective cohort study of HER2/neu-positive breast cancer patients who received a pertuzumab-containing regimen between January 2012 and August 2015. We calculated the risk of diarrhea with 95% confidence limits (CLs), and then used two-sample t-tests to compare the risk between trials and actual practice. RESULTS: A total of 27 patients in the study cohort received a pertuzumab-containing treatment regimen for HER2/neu-positive breast cancer. The overall risk of all-grade and severe diarrhea in actual practice was 70% (95% CLs 55-90%) and 37% (95% CLs 20-66%), respectively. No severe diarrhea was observed in the metastatic setting, and the risk of all-grade diarrhea (44%, 95% CLs 21-92%) was similar to the CLEOPATRA study (67%). The risk of all-grade diarrhea in the neo-adjuvant setting was 83% (95% CLs 68-100%), compared to 46% in the NeoSphere trial (p = 0.03). The risk of severe diarrhea (Grade 3-4) in the neo-adjuvant setting was 47% (95% CLs 27-80%) versus 6% in the NeoSphere (p < 0.0001) and 12% in the TRYPHAENA (p < 0.01) trials. CONCLUSIONS: The risk of all-grade and severe diarrhea associated with neoadjuvant pertuzumab use for HER2/neu-positive breast cancer was greater in actual practice than in trials.

Patterns of bevacizumab use in patients with glioblastoma: an online survey among experts in neuro-oncology.

BACKGROUND: Bevacizumab (BEV) received accelerated FDA approval in 2009 for the treatment of recurrent glioblastoma (rGBM). Unfortunately, prospective randomized controlled phase 3 studies (AVAglio and Radiation Therapy Oncology Group 0825 in newly diagnosed, European Organisation for Research and Treatment of Cancer 26101 in rGBM) failed to show an overall survival benefit with BEV added to standard therapy. In light of these data, we aimed to capture current utilization patterns and perceived value of BEV in the treatment of GBM among experts in the field. METHODS: An online questionnaire comprising 14 multiple choice questions was sent out in spring 2017 to 207 oncologists/neuro-oncologists treating patients with GBM at all National Cancer Institute-designated cancer centers in the United States. RESULTS: Sixty-two of 207 (30%) invitees responded (by training, 70% neuro-oncologists, 20% medical oncologists, 10% pediatric oncologists/neuro-oncologists). Participants reported use of BEV most frequently in rGBM for control of edema (85% of respondents) and/or when no other treatment options were available (68%). BEV is rarely used in newly diagnosed GBM (<5% of cases by 78% respondents and in 5% to 10% cases by 15% respondents). Sixty-six percent of participants indicated that they thought BEV improved symptoms, 30% that it improved symptoms and survival, 3% that it had no benefit in GBM patients. CONCLUSION: In this cross-sectional online survey we found that among neuro-oncology experts in the United States in 2017, BEV is predominantly utilized in select patients with rGBM, and is only rarely used in a small subgroup of patients with newly diagnosed GBM for control of edema. The low response rate may have introduced a nonresponse bias.

Pneumocystis jirovecii prophylaxis in patients treated for high-grade gliomas: a survey among neuro-oncologists.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is a known complication in patients with high-grade gliomas (HGGs) who are treated with radiation and chemotherapy. PJP prophylaxis is commonly recommended, but there are currently no clear guidelines regarding duration of treatment and choice of drugs. This study aimed to assess current practice patterns of PJP prophylaxis among neuro-oncologists. METHODS: An online survey of 14 multiple choice questions was sent to 207 neuro-oncologists and medical oncologists treating brain cancers at all National Cancer Institute-designated cancer centers in the United States. Recipients were identified via a search of the cancer centers' websites. RESULTS: Sixty-one invited experts completed the survey (response rate 29%; of these, 72% were neuro-oncologists, 18% were medical oncologists, and 10% were pediatric neuro- or medical oncologists). Seventy percent of respondents stated that they routinely prescribe PJP prophylaxis, while 7% do not provide prophylaxis. Eighty-one percent of respondents use absolute lymphocyte count (ALC) to assess lymphopenia and 13% also monitor CD4 lymphocyte counts during prophylaxis. The most commonly used first-line agent is trimethoprim-sulfamethoxazole (88% of respondents), followed by pentamidine (6%). Discontinuation of PJP prophylaxis is determined by the following: count recovery (33% by ALC; 18% by CD4 lymphocyte counts), radiation completion (23%), and chemotherapy completion (7%). Glucose-6-phosphate dehydrogenase levels were routinely checked by only 13% of respondents. CONCLUSIONS: PJP prophylaxis is commonly used in HGG patients, but there are large variations in practice patterns, including the duration of prophylaxis. As consideration for PJP prophylaxis affects all patients with HGG, standardization of prophylaxis should be formally addressed.

Kidney Cancer: Toxicity Management, Symptom Control, and Palliative Care.

The challenges of managing the toxicities associated with the current armamentarium to combat kidney cancer continue to grow. It is therefore paramount for providers to not only have knowledge of the disease, but to also have an understanding of the potential adverse effects associated with the various treatments. In addition, it is important to incorporate palliative care strategies to help manage symptoms, improve quality of life, and support patients and their families throughout the continuum of the disease. This article will discuss the general toxicities and symptomatic issues encountered in patients with kidney cancer who are receiving targeted therapies and immunotherapies. It will also define the components of palliative care and its benefits. The recommendations in this article are from source documentation noted in various guidelines of the Oncology Nursing Society, ASCO, the National Comprehensive Cancer Network, and the Society for Immunotherapy of Cancer. We feel it is appropriate to modify and individualize management as deemed necessary to provide the best outcome for patients and their families.