Kathryn Maree Field

Chemotherapy Dosing Strategies in the Obese, Elderly, and Thin Patient: Results of a Nationwide Survey

PURPOSE Determining the optimal starting dose of chemotherapy (CHT) presents a considerable challenge when using body-surface area (BSA)-based dosing, particularly in obese, elderly, or thin patients. We sought to document the range of approaches employed when administering CHT to these patients. METHODS A questionnaire was developed by a panel of oncologists and mailed to all members of the Medical Oncology Group of Australia. RESULTS From 315 oncologists, 188 responded (response rate 59.7%). BSA-based dosing is standard practice for 176 (97.2%) of the responding oncologists. In the adjuvant disease setting, 23 (12.7%) use ideal rather than actual body weight (BW) to calculate BSA, or choose whichever is less. When treating obese patients, only 6.1% of respondents routinely use actual BW. Of the remainder, 69.5% either cap the dose at 2 m(2) or use ideal BW. In underweight patients, 95% (n = 171) routinely calculate BSA using actual BW. Forty one respondents (22.7%) routinely reduce dose in the fit elderly. CONCLUSION This analysis of BSA-based CHT dosing methods demonstrates significant variability in practice. Based on evidence from adjuvant studies showing that actual BSA-based dosing is desirable, a substantial number of Australian patients are being underdosed. Further education, together with ongoing research, is required to optimize individualized dosing for efficacy and tolerability.

Part I: Liver function in oncology: biochemistry and beyond

The liver has a key role in the metabolism (ie, inactivation or activation) of many commonly used anticancer agents-cytotoxics or new biological agents. Therefore, assessment of liver function is a fundamental part of initial work-up and management of patients with cancer. An understanding of the meaning of conventional serum biochemical testing of liver function and status, what variables they are measuring, and usefulness for chemotherapy dosing is essential. Emerging awareness of the drawbacks of conventional serum biochemical testing and further understanding of the intricacies of liver function is leading to the development of alternative strategies for appropriate chemotherapy regimens and dosing. We present an overview of assessment of liver function and chemotherapy dosing. We consider the use of serum liver biochemical testing to predict liver function, potential causes of biochemical abnormalities in patients with cancer, and chemotherapy drugs that are associated with hepatotoxicity. Part II will overview the current knowledge surrounding chemotherapy dosing in the setting of liver dysfunction; as well as alternative tests of hepatic metabolic function that are beginning to be used as strategies for appropriate individualised chemotherapy administration.

Incidence of catheter-related bloodstream infection among patients with a needleless, mechanical valve-based intravenous connector in an Australian hematology-oncology unit.

There are few Australian data on the incidence of catheter-associated bloodstream infection (BSI) among patients in hematology-oncology units. We found an increase in catheter-associated BSI rates coincident with the introduction of a mechanical valve connector (2.6 infections vs 5.8 infections per 1,000 catheter-days; incidence rate ratio, 2.2; P=.031).

Part II: Liver function in oncology: towards safer chemotherapy use

The liver is fundamentally important in drug metabolism. In oncology, the astute clinician must not only understand the meaning and limitations of commonly ordered liver biochemical tests, but also be aware of which anticancer agents might induce liver dysfunction, and of the strategies for appropriate dosing of patients with pre-existing liver dysfunction. In part I of our Review, we highlighted both the importance and inadequacies of identifying serum biochemical liver abnormalities in oncology; we also discussed a lack of routine formal investigation of liver function. We summarised chemotherapy-related hepatotoxicity and other causes of liver toxic effects in patients with cancer. Here in part II, we discuss trials that have specifically assessed chemotherapy dosing strategies in the setting of overt biochemical liver dysfunction and we note their recommendations. Furthermore, we review other assessments of liver metabolic and excretory function, particularly in the setting of chemotherapy drug handling. We discuss the potential use of these metabolic probes in practice.

Bevacizumab and glioblastoma: Scientific review, newly reported updates, and ongoing controversies

Anti‐angiogenic therapy for glioblastoma has been in the spotlight for several years, as researchers and clinicians strive to find agents with meaningful efficacy against glioblastoma. Bevacizumab in particular, in the second half of the last decade, became the most significant breakthrough in anti‐glioblastoma therapy since temozolomide. Optimism for bevacizumab has been somewhat challenged given recent clinical trials that have raised questions regarding its clinical effectiveness, the optimal timing of its use and the validity of endpoints, among other issues. In addition, uncertainty has recently arisen regarding the effects of bevacizumab on quality of life and neurocognitive function, two key clinical endpoints of unquestionable significance among glioblastoma patients. In this review, we highlight these controversies and other recent work related to bevacizumab for glioblastoma. Cancer 2015;121:997–1007.

Randomized phase 2 study of carboplatin and bevacizumab in recurrent glioblastoma

BACKGROUND The optimal use of bevacizumab in recurrent glioblastoma (GBM), including the choice of monotherapy or combination therapy, remains uncertain. The purpose of this study was to compare combination therapy with bevacizumab monotherapy. METHODS This was a 2-part randomized phase 2 study. Eligibility criteria included recurrent GBM after radiotherapy and temozolomide, no other chemotherapy for GBM, and Eastern Cooperative Oncology Group performance status 0-2. The primary objective (Part 1) was to determine the effect of bevacizumab plus carboplatin versus bevacizumab monotherapy on progression-free survival (PFS) using modified Response Assessment in Neuro-Oncology criteria. Bevacizumab was given every 2 weeks, 10 mg/kg; and carboplatin every 4 weeks, (AUC 5). On progression, patients able to continue were randomized to continue or cease bevacizumab (Part 2). Secondary endpoints included objective radiological response rate (ORR), quality of life, toxicity, and overall survival (OS). RESULTS One hundred twenty-two patients (median age, 55y) were enrolled to Part 1 from 18 Australian sites. Median follow-up was 32 months, and median on-treatment time was 3.3 months. Median PFS was 3.5 months for each arm (hazard ratio [HR]: 0.92, 95% CI: 0.64-1.33, P = .66). ORR was 14% (combination) versus 6% (monotherapy) (P = .18). Median OS was 6.9 (combination) versus 7.5 months (monotherapy) (HR: 1.18, 95% CI: 0.82-1.69, P = .38). The incidence of bevacizumab-related adverse events was similar to prior literature, with no new toxicity signals. Toxicities were higher in the combination arm. Part 2 data (n = 48) will be reported separately. CONCLUSIONS Adding carboplatin resulted in more toxicity without additional clinical benefit. Clinical outcomes in patients with recurrent GBM treated with bevacizumab were inferior to those in previously reported studies. CLINICAL TRIALS REGISTRATION NR ACTRN12610000915055.

Locally advanced and metastatic gastric cancer: current management and new treatment developments.

The management of gastric cancer remains a challenge. In recent years, the most important advances have been achieved in the adjuvant setting for patients with locally advanced disease, where significant survival benefits have been demonstrated for both perioperative chemotherapy and adjuvant chemoradiotherapy. These findings have changed the standard of care for patients with resectable disease.In the setting of metastatic gastric cancer, the development of new cytotoxic regimens must consider the balance between efficacy and toxicity in patients whose overall prognosis is poor. Major advances in recent years include the development of orally administered fluoropyrimidine analogues, which can be used in place of intravenous fluorouracil, and the addition of newer agents such as oxaliplatin and docetaxel, which have demonstrated efficacy in patients with advanced disease. Targeted therapies have had a major impact on the management of certain malignancies, and while their evaluation in the treatment of advanced gastric cancer remains early, it is likely that these agents will continue to be developed and studied in combination with chemotherapy.This article reviews recent advances in the use of chemotherapy for advanced gastric cancer. Targeted therapies, their mechanisms of action and emerging data supporting their use in gastric cancer are also discussed. The two randomized phase III trials supporting adjuvant therapy for locally advanced, resectable gastric cancer are discussed in detail, together with strategies for future trials in this area. Overall, there remains optimism that further incremental gains will be achieved with future studies combining chemotherapy, radiotherapy and targeted therapies, both in the adjuvant and metastatic disease settings.

Clinical trial participation and outcome for patients with glioblastoma: Multivariate analysis from a comprehensive dataset

Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. Although multiple clinical and tumor-related variables affect survival outcomes, the effect of clinical trial participation has not been explored. The aim of this study was to determine whether clinical trial participation improves outcome for patients with GBM. Data from patients with GBM were accessed from a dataset collected over 12 years (1998-2010) at two institutions. Univariable and multivariate logistic regression analyses were performed to look for relationships between clinical trial participation, other baseline clinical and sociodemographic variables and overall survival (OS). In total, 542 patients were identified and included in the analysis; median age was 62 years. Sixty-one patients (11%) were enrolled in a clinical trial. Clinical trial enrollment was associated with improved median survival (14.5 months compared to 6.3 months, p < 0.001) and this difference remained significant in multivariate analysis (hazard ratio 0.67, p = 0.046). Age, poor performance status and operation type were also independent predictors for OS in multivariate analysis. Disease site, socioeconomic status and co-morbidity did not affect survival outcome. This is the first study in patients with GBM to suggest a survival benefit from clinical trial participation, independent of age and performance status; while also confirming the importance of other previously reported prognostic factors. This should encourage clinicians to offer trial therapies to patients with GBM and encourage patients to participate in available studies.

Predictors of the use of complementary and alternative medicine (CAM) by women at high risk for breast cancer

BACKGROUND Few data exist regarding the use of complementary and alternative medicine (CAM) by unaffected women at high risk of breast cancer. METHODS Self-reported CAM use by women from multiple-case breast cancer families was obtained by questionnaire. Factors associated with CAM use were assessed using multiple logistic regression. RESULTS Of 892 women, 55% (n=489) used CAM, 6% (n=53) specifically to prevent cancer. CAM use was independently associated with tertiary education level (OR 2.56, 95% CI 1.83-3.58, p<0.001), greater physical activity (OR 1.05 per hour of physical activity/week, 95% CI 1.00-1.10, p=0.049), greater anxiety (OR 1.92, 95% CI 1.16-3.16, p=0.01), not currently smoking (OR 0.64, 95% CI 0.42-0.97, p=0.037) and lower perceived BC risk (OR 0.82 per 20 percentage points, 95% CI 0.72-0.94, p=0.005). CONCLUSIONS The majority of high-risk women use CAM, but mostly for reasons other than cancer prevention. Most predictors of CAM use are consistent with the limited literature for women at high risk for cancer.

Dose rounding of chemotherapy in colorectal cancer: an analysis of clinician attitudes and the potential impact on treatment costs.

Aim:  The aims of this study were to calculate theoretical cost savings of oxaliplatin dose rounding in colorectal cancer (CRC), and to assess clinician attitudes to chemotherapy dose rounding.