Carboplatin dosing in the treatment of ovarian cancer: An NRG oncology group study.

OBJECTIVE: To determine the effects of using National Comprehensive Cancer Network (NCCN) guidelines to estimate renal function on carboplatin dosing and explore adverse effects associated with a more accurate estimation of lower creatinine clearance (CrCl). METHODS: Retrospective data were obtained for 3830 of 4312 patients treated on GOG182 (NCT00011986)-a phase III trial of platinum-based chemotherapy for advanced-stage ovarian cancer. Carboplatin dose per patient on GOG182 was determined using the Jelliffe formula. We recalculated CrCl to determine dosing using Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault (with/without NCCN recommended modifications) formulas. Associations between baseline CrCl and toxicity were described using the area under the receiver operating characteristic curve (AUC). Sensitivity and positive predictive values described the model's ability to discriminate between subjects with/without the adverse event. RESULTS: AUC statistics (range, 0.52-0.64) showed log(CrClJelliffe) was not a good predictor of grade ≥3 adverse events (anemia, thrombocytopenia, febrile neutropenia, auditory, renal, metabolic, neurologic). Of 3830 patients, 628 (16%) had CrCl <60 mL/min. Positive predictive values for adverse events ranged from 1.8%-15%. Using the Cockcroft-Gault, Cockcroft-Gault with NCCN modifications, and MDRD (instead of Jelliffe) formulas to estimate renal function resulted in a >10% decrease in carboplatin dosing in 16%, 32%, and 5.2% of patients, respectively, and a >10% increase in carboplatin dosing in 41%, 9.6% and 12% of patients, respectively. CONCLUSION: The formula used to estimate CrCl affects carboplatin dosing. Estimated CrCl <60 mL/min (by Jelliffe) did not accurately predict adverse events. Efforts continue to better predict renal function. Endorsing National Cancer Institute initiatives to broaden study eligibility, our data do not support a minimum threshold CrCl <60 mL/min as an exclusion criterion from clinical trials.

Biosimilars and cancer treatment of older patients.

Biosimilar monoclonal antibodies are being developed globally to meet clinical demand in oncology and potentially provide greater access to biologic therapies for patients with cancer, including older patients. In this supplement, we present an overview of the development, approval requirements, and characteristics of biosimilar monoclonal antibodies that may help practicing oncologists and other healthcare providers to acquire familiarity with this new group of therapeutic biologic agents. Furthermore, we review and discuss some of the challenges and potential strategies for the management of older patients with cancer, who represent an increasing population in many countries.

Effect of Pretreatment Renal Function on Treatment and Clinical Outcomes in the Adjuvant Treatment of Older Women With Breast Cancer: Alliance A171201, an Ancillary Study of CALGB/CTSU 49907.

PURPOSE: CALGB 49907 showed the superiority of standard therapy, which included either cyclophosphamide/doxorubicin (AC) or cyclophosphamide/methotrexate/fluorouracil over single-agent capecitabine in the treatment of patients age ≥ 65 with early-stage breast cancer. The treatment allowed dosing adjustments of methotrexate and capecitabine for pretreatment renal function. The purpose of the current analysis was to assess the relationship between pretreatment renal function and five end points: toxicity, dose modification, therapy completion, relapse-free survival, and overall survival. METHODS: Pretreatment renal function was defined as creatinine clearance (CrCl) using the Cockcroft-Gault equation. Multivariable logistic and proportional hazards regression were used to model separately for each regimen the relationship between CrCl and the first three binary end points and the last two time-to-event end points, respectively, after adjusting for variables of prognostic importance. RESULTS: Six hundred nineteen assessable patients were analyzed. The incidence of stage III (moderate) or stage IV (severe) renal dysfunction was 72%, 64%, and 75% for treatment with cyclophosphamide/methotrexate/fluorouracil, AC, and capecitabine, respectively. There was no relationship for any regimen between pretreatment renal function and the five end points. For AC, as CrCl increased, the odds of nonhematologic toxicity decreased (P = .008), whereas for capecitabine, as CrCl increased, the odds of experiencing toxicity of any type also increased (P = .035). Patients with renal insufficiency who received dose modifications were not at increased risk for complications compared with those who did not have renal insufficiency and received a full dose. CONCLUSION: Excluding from clinical trials patients with renal insufficiency but good performance status on the basis of concern of excessive hematologic toxicity or poor outcomes may not be justified with appropriate dosing modifications. Results should be considered in the design of clinical trials for older patients.

Use of complementary medications among older adults with cancer.

BACKGROUND: Little is known about complementary medication use among older adults with cancer, particularly those who are receiving chemotherapy. The objective of this study was to evaluate the prevalence of complementary medication use and to identify the factors associated with its use among older adults with cancer. METHODS: The prevalence of complementary medication use (defined as herbal agents, minerals, or other dietary supplements, excluding vitamins) was evaluated in a cohort of adults aged ≥65 years who were about to start chemotherapy for their cancer. The associations between complementary medication use and patient characteristics (sociodemographics; comorbidities; and functional, nutritional, psychological, and cognitive status), medication use (number of medications and concurrent vitamin use), and cancer characteristics (type and stage) were analyzed. RESULTS: The cohort included 545 patients (mean age, 73 years; range, 65-91 years; 52% women) with cancer (61% stage IV). Seventeen percent of these patients (N = 93) reported using ≥1 complementary medication; the mean number of complementary medications among users was 2 (range, 1-10 medications). Complementary medication use was associated with 1) earlier cancer stage (29% had stage I-II disease vs 17% with stage III-IV disease; odds ratio [OR], 2.05; 95% confidence interval [CI], 1.21-3.49) and 2) less impairment with instrumental activities of daily living (OR, 1.39; 95% CI, 1.12-1.73). CONCLUSIONS: Complementary medication use was reported by 17% of older adults with cancer and was more common among those who had less advanced disease (i.e., those receiving adjuvant, potentially curative treatment) and higher functional status. Further studies are needed to determine the association between complementary medication use and cancer outcomes among older adults.

Guidelines for the treatment of elderly cancer patients.

BACKGROUND: The management of elderly patients with cancer is influenced by several factors that can vary widely among aging individuals. As the proportion of elderly individuals increases, the need for specific care guidelines for this population is critical. The National Comprehensive Cancer Network (NCCN) has developed guidelines to address these factors when formulating optimal treatment regimens for elderly patients and to avoid significant toxicity and maintain their quality of life. METHODS: Factors that influence the appropriate treatment choices for the elderly, such as functional status, comorbidity, polypharmacy, and the presence of anemia, are reviewed, and the guidelines developed by the NCCN for treatment elderly patients are discussed. RESULTS: The guidelines address these factors when defining the goal of therapy and formulating individualized treatment approaches for the elderly to provide optimal care for these patients, avoid significant toxicity, and maintain their quality of life. CONCLUSIONS: The goal of therapy must be clearly defined, whether survival, remission, cure, or palliation of symptoms. Enrollment of elderly cancer patients onto clinical trials is encouraged so the guidelines can be validated.

Pharmacokinetic considerations of oral chemotherapy in elderly patients with cancer.

Persons over the age of 65 years are the fastest growing segment of the US population. In the next 30 years they will comprise over 20% of the population. Fifty per cent of all cancers occur in this age group and therefore there will be an expected rise in the total cancer burden. There has been an increasing trend over the past 20 years toward the use of oral chemotherapy. This change has been encouraged by the need to decrease the costs of chemotherapy administration, patient preferences and quality of life issues. Factors that must be considered with oral chemotherapy administration include limitations of saturability of absorption, patient compliance and pharmacokinetic/pharmacodynamic changes which occur in elderly patients. Interpatient variability and drug metabolism, particularly age-related changes in drug metabolism are being studied. The cytochrome P450 system has been intensively studied because of its importance with regard to chemotherapeutic drugs. This article reviews these issues and provides details regarding specific drugs including temozolomide, thalidomide, topotecan, the fluoropyrimidines, etoposide, hydroxycarbamide (hydroxyurea), tamoxifen, and alkylating drugs. Complementary and alternative therapies are also discussed.