Evaluation of chemotherapy-induced peripheral neuropathy using current perception threshold and clinical evaluations.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is increasing with introduction of new and combination cancer pharmacotherapies. This study evaluated associations between clinical and self-report measurements and current perception threshold (CPT), a neuroselective measure of sensory nerve function that may detect asymptomatic CIPN damage. METHODS: Data for this secondary analysis were from a prospective, observational study using CPT to evaluate CIPN. Bivariate mixed models, accounting for the intraclass correlation between repeated patient assessments, were used to assess the relationship between CPT at each frequency (5, 250, and 2,000 Hz) and each subjective measure (Neuropathic Pain Scale, FACT-GOGntx) and objective measurement (quantitative sensory testing, deep tendon reflexes, and grip strength). RESULTS: A total of 29 chemotherapy-naïve subjects with various cancer types had a mean age of 56.7 (SD 10.4); nine subjects developed CIPN grade >1 using NCI CTC-AE criteria. Cold detection thresholds were inversely associated with CPT 5 [b(95 % CI) = -2.5(-4.5, -0.5)] and CPT 2,000 [-7.5(-11.8, -3.3)] frequencies. FACT GOG-ntx quality of life (QoL) scale and neurotoxicity and function subscales were inversely associated with CPT 2,000 [-1.8 (-3.5, -0.05), -2.2 (-4.2, -0.2), and -5.4 (-9.8, -0.9), respectively], indicating worsening QoL, impairment, and function as hypoesthesia increases. CONCLUSIONS: CPT 2,000 may identify impending worsening of patient-reported outcomes such as QoL.

Out-of-pocket health care expenditure burden for Medicare beneficiaries with cancer.

BACKGROUND: There is increasing concern regarding the financial burden of care on cancer patients and their families. Medicare beneficiaries often have extensive comorbidities and limited financial resources, and may face substantial cost sharing even with supplemental coverage. In the current study, the authors examined out-of-pocket (OOP) spending and burden relative to income for Medicare beneficiaries with cancer. METHODS: This retrospective, observational study pooled data for 1997 through 2007 from the Medicare Current Beneficiary Survey linked to Medicare claims. Medicare beneficiaries with newly diagnosed cancer were selected using claims-based diagnoses. Generalized linear models were used to estimate OOP spending. Logistic regression models identified factors associated with a high OOP burden, defined as spending > 20% of one's income during the cancer diagnosis and subsequent year. RESULTS: The cohort included 1868 beneficiaries with and 10,047 without cancer. Compared with the noncancer cohort, cancer patients were older, had more comorbidities, and were more likely to lack supplemental coverage. The mean OOP spending for cancer patients was $4727. Cancer patients faced an adjusted $976 (P < .01) incremental OOP spending. Greater than one-quarter (28%) of beneficiaries with cancer experienced a high OOP burden compared with 16% of beneficiaries without cancer (P < .001). Supplemental insurance and higher income were found to be protective against a high OOP burden, whereas assets, comorbidity, and receipt of cancer-directed radiation and antineoplastic therapy were associated with a higher OOP burden. CONCLUSIONS: Medicare beneficiaries with cancer face a higher OOP burden than their counterparts without cancer; some of the higher burden was explained by the higher comorbidity burden and lack of supplemental insurance noted among these patients. Financial pressures may discourage some elderly patients from pursuing treatment.

Use and spending on antineoplastic therapy for Medicare beneficiaries with cancer.

BACKGROUND: Oral antineoplastic drugs, not generally covered by Medicare Part B, have assumed an increasingly important role in cancer treatment. OBJECTIVE: We examined use and spending on infused/injected (Part B covered) and non-Part B antineoplastic agents in a Medicare beneficiary population with cancer, and the effect of supplemental insurance. RESEARCH DESIGN: This retrospective, observational study used pooled 1997-2007 data from the Medicare Current Beneficiary Survey, linked to Medicare claims. Logistic regression models identified factors associated with antineoplastic use. Generalized linear models were used to estimate spending among antineoplastic users. POPULATION STUDIED: A total of 1836 Medicare beneficiaries with newly diagnosed cancer were selected based on the presence of claims-based diagnoses after a 12-month washout period. RESULTS: Five hundred fifty-nine (31.0%) Medicare beneficiaries received antineoplastic therapy; 395 (21.3%) used Part B, 253 (14.6%) used non-Part B antineoplastics. Spending per user was $7841 (any), $10,364 (Part B), and $1535 for non-Part B antineoplastics. Supplemental insurance was associated with antineoplastic use. Primary cancer site and age were key predictors of spending among users. Spending on non-Part B antineoplastics increased during 2006-2007 relative to 2004-2005 but time trends were not significant in multivariate analysis. CONCLUSIONS: Antineoplastic therapy use by Medicare beneficiaries is sensitive to the presence but not type of supplemental insurance. Non-Part B therapy was used by a relatively large proportion of beneficiaries with cancer receiving therapy, although spending was less than for Part B therapy. Monitoring the role of supplemental insurance, and particularly the role of Medicare Part D is a critical area for ongoing research.

Comparative and cost-effectiveness of oxaliplatin-based or irinotecan-based regimens compared with 5-fluorouracil/leucovorin alone among US elderly stage IV colon cancer patients.

BACKGROUND: Clinical trials have shown a statistically significant disease-free survival benefit of oxaliplatin-based or irinotecan-based combination regimens for stage IV colon cancer. Less is known regarding the comparative effectiveness and cost-effectiveness of these agents among elderly patients. Whether the benefits of these agents justify the additional costs for elderly Medicare recipients is particularly policy relevant after US health care reform. METHODS: A cost-effectiveness analysis of oxaliplatin-based or irinotecan-based combination therapy versus 5-fluorouracil/leucovorin alone in elderly stage IV colon cancer patients was performed from a US Medicare perspective. Survival and direct medical costs were estimated using Surveillance, Epidemiology, and End Results-Medicare data sets for patients diagnosed from 2002 to 2005 with follow-up through 2007. Incremental cost-effectiveness ratios (ICERs) were calculated as costs per life-year gained, with sensitivity analysis estimating the cost per quality-adjusted life-year (QALY). RESULTS: Median improved overall survival with 5-fluorouracil/leucovorin alone, or irinotecan-based or oxaliplatin-based combination therapy was 0.99, 1.07, and 1.47 life-years, respectively. Costs per life-year gained for oxaliplatin-based or irinotecan-based combination regimens compared with 5-fluorouracil/leucovorin alone were $78,181 and $267,938, respectively. ICERs comparing oxaliplatin-based to irinotecan-based regimens were $40,230 per life-year gained or $160,920 per QALY. CONCLUSIONS: Oxaliplatin-based or irinotecan-based combination therapy improves overall survival but also substantially increases direct medical costs compared with 5-fluorouracil/leucovorin alone when used in elderly US patients with stage IV colon cancer. Oxaliplatin-based regimens are more cost-effective than irinotecan-based regimens for treatment of elderly stage IV colon cancer patients in terms of cost per life-year gained, but not in terms of cost per QALY.

Trends in disparities in receipt of adjuvant therapy for elderly stage III colon cancer patients: the role of the medical oncologist evaluation.

BACKGROUND: Race disparities in adjuvant chemotherapy for stage III colon cancer patients have been documented, and medical oncologist evaluation is a critical step in the treatment process. Recent healthcare system and environmental changes may have reduced treatment gaps. OBJECTIVES: To examine differential rates of oncologist evaluation and conditional treatment, by race, and to determine whether changing evaluation and treatment patterns reduced disparities. RESEARCH DESIGN: Retrospective analysis of Surveillance Epidemiology and End Results-Medicare registry, enrollment, and claims data. SUBJECTS: Patients age >65, white or African American race, diagnosed with American Joint Committee on Cancer stage III colon cancer between 1997 and 2002. N = 7176. KEY MEASURES: Oncology specialty evaluation and management visit or chemotherapy claim; receipt of 5-fluorouracil based chemotherapy. Time periods are grouped into early (1997-1998), middle (1999-2000), and late (2001-2002). RESULTS: Initial adjusted oncologist evaluation rates were higher for whites compared with African American patients (58.7% vs. 42.9%), but changes over time reduced the race gap substantially. We did not find significant race-time trends in treatment rates conditional on oncologist evaluation. CONCLUSIONS: Race disparities in medical oncologist evaluations diminished over time, possibly in response to increased provider supply or changing patient and provider attitudes, but there was no parallel reduction in disparities in conditional treatment rates. Projected decreases in oncologist supply suggest the need for further research on this relationship. Research on the role of supplemental medical insurance on disparities in treatment is needed, particularly as the cost of recommended adjuvant therapy increases.

Toxicity of aromatase inhibitors.

Adjuvant hormonal therapy in hormone receptor-positive breast cancer is used for the prevention of disease recurrence and prolongation of survival. Aromatase inhibitors are increasingly being used for this purpose. Numerous studies now reveal their benefits over tamoxifen while demonstrating a markedly different toxicity profile. With greater use, a better understanding of the long-term effects of aromatase inhibitors on the prevention of cancer recurrence and on their long-term effects on chronic comorbid conditions will develop. Recognizing and understanding these toxicities, as well as the differences among the various aromatase inhibitors, will be crucial for all clinicians. When choosing the type of adjuvant hormonal therapy for each individual patient, comorbidities and quality-of-life parameters must be considered. In addition, ongoing studies evaluating these agents directly should reveal differences among them that may aid in determining the principal agent for use in this setting. In this article, we review the known toxicity profile of aromatase inhibitors and the current guidelines that exist in the diagnoses and management of these toxicities.

A phase I dose-escalation study of MEDI-575, a PDGFRα monoclonal antibody, in adults with advanced solid tumors.

PURPOSE: The purpose of the study was to evaluate safety and determine the maximum tolerated dose (MTD) of MEDI-575, a fully human monoclonal antibody that selectively binds to platelet-derived growth factor receptor-α (PDGFRα), in patients with advanced solid tumors. METHODS: This phase I multicenter, open-label, single-arm study enrolled adults in a 3 + 3 dose escalation design to receive MEDI-575 (3, 6, 9, 12, or 15 mg/kg) once weekly (QW) until toxicity or disease progression occurred. One 0.5-mg/kg dose was given before the first dose in the 3-mg/kg cohort to determine pharmacokinetics (PK) and pharmacodynamics under unsaturated conditions. After completion of dose escalation in the QW cohorts, patients were enrolled in two additional cohorts and received MEDI-575 25 or 35 mg/kg every 3 weeks (Q3W). Secondary measures included assessments of PK, immunogenicity, and antitumor activity. RESULTS: A total of 35 patients received MEDI-575 QW (n = 23) or Q3W (n = 12). Most treatment-related adverse events were grade 1 or 2 in severity across all dose levels, with fatigue (n = 12) and nausea (n = 8) being reported most frequently. With no reports of dose-limiting toxicities (DLTs), the MTD was not reached. MEDI-575 exhibited a nonlinear PK profile and increased plasma platelet-derived growth factor-AA levels in a dose-dependent manner with limited immunogenicity. Stable disease was reported as the best tumor response in 9 of 29 evaluable patients; however, no objective responses were reported. CONCLUSION: Administration of MEDI-575 QW or Q3W resulted in a favorable safety profile, including a lack of DLTs, but without evidence of antitumor activity in patients with refractory solid tumors.

A novel approach to improve health status measurement in observational claims-based studies of cancer treatment and outcomes.

OBJECTIVES: To develop and provide initial validation for amultivariate, claims-based prediction model for disability status (DS), a proxymeasure of performance status (PS), among older adults. The model was designed to augment information on health status at the point of cancer diagnosis in studies using insurance claims to examine cancer treatment and outcomes. MATERIALS AND METHODS: We used data from the 2001­2005 Medicare Current Beneficiary Survey (MCBS), with observations randomly split into estimation and validation subsamples. We developed an algorithm linking self-reported functional status measures to a DS scale, a proxy for the Eastern Cooperative Oncology Group (ECOG) PS scale. The DS measure was dichotomized to focus on good [ECOG 0­2] versus poor [ECOG 3­4] PS. We identified potential claims-based predictors, and estimated multivariate logistic regression models, with poor DS as the dependent measure, using a stepwise approach to select the optimal model. Construct validity was tested by determining whether the predicted DS measure generated by the model was a significant predictor of survival within a validation sample from the MCBS. RESULTS AND CONCLUSION: One-tenth of the beneficiaries met the definition for poor DS. The base model yielded high sensitivity (0.79) and specificity (0.92); positive predictive value=48.3% and negative predictive value=97.8%, c-statistic=0.92 and good model calibration. Adjusted poor claims-based DS was associated with an increased hazard of death (HR=3.53, 95% CI 3.18, 3.92). The ability to assess DS should improve covariate control and reduce indication bias in observational studies of cancer treatment and outcomes based on insurance claims.

Analysis of local control in patients receiving IMRT for resected pancreatic cancers.

PURPOSE: Intensity-modulated radiotherapy (IMRT) is increasingly incorporated into therapy for pancreatic cancer. A concern regarding this technique is the potential for geographic miss and decreased local control. We analyzed patterns of first failure among patients treated with IMRT for resected pancreatic cancer. METHODS AND MATERIALS: Seventy-one patients who underwent resection and adjuvant chemoradiation for pancreas cancer are included in this report. IMRT was used for all to a median dose of 50.4 Gy. Concurrent chemotherapy was 5-FU-based in 72% of patients and gemcitabine-based in 28%. RESULTS: At median follow-up of 24 months, 49/71 patients (69%) had failed. The predominant failure pattern was distant metastases in 35/71 patients (49%). The most common site of metastases was the liver. Fourteen patients (19%) developed locoregional failure in the tumor bed alone in 5 patients, regional nodes in 4 patients, and concurrently with metastases in 5 patients. Median overall survival (OS) was 25 months. On univariate analysis, nodal status, margin status, postoperative CA 19-9 level, and weight loss during treatment were predictive for OS. On multivariate analysis, higher postoperative CA19-9 levels predicted for worse OS on a continuous basis (p < 0.01). A trend to worse OS was seen among patients with more weight loss during therapy (p = 0.06). Patients with positive nodes and positive margins also had significantly worse OS (HR for death 2.8, 95% CI 1.1-7.5; HR for death 2.6, 95% CI 1.1-6.2, respectively). Grade 3-4 nausea and vomiting was seen in 8% of patients. Late complication of small bowel obstruction occurred in 4 (6%) patients. CONCLUSIONS: This is the first comprehensive report of patterns of failure among patients treated with adjuvant IMRT for pancreas cancer. IMRT was not associated with an increase in local recurrences in our cohort. These data support the use of IMRT in the recently activated EORTC/US Intergroup/RTOG 0848 adjuvant pancreas trial.

Comparative effectiveness of different chemotherapeutic regimens on survival of people aged 66 and older with stage III colon cancer: a "real world" analysis using Surveillance, Epidemiology, and End Results-Medicare data.

OBJECTIVES: To compare the effectiveness and utilization trends of irinotecan (IRI)-based and oxaliplatin (OX)-based regimens with those of 5-fluorouracil and leucovorin (5FU/LV) alone in people aged 66 and older with Stage III colon cancer. DESIGN: Retrospective cohort study. SETTING: Data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare data. PARTICIPANTS: People with Stage III surgically resected colon cancer who received adjuvant chemotherapy were categorized into 5FU/LV-alone (n = 3,581), OX-based regimen (n = 814), and IRI-based regimen (n = 219) subgroups. MEASUREMENTS: Multivariable Cox proportional hazards models examined the effect of chemotherapies on overall survival, colon cancer-specific survival, and non-colon cancer-specific survival. RESULTS: Use of the OX-based regimen increased, and use of the 5FU/LV-alone and IRI-based regimens decreased over time. OX was statistically significantly associated with longer overall survival (hazard ratio (HR) = 0.73, 95% confidence interval (CI) = 0.62-0.86, P < .001) and colorectal cancer-specific survival (HR = 0.39, 95% CI, 0.28-0.55, P < .001) than 5FU/LV alone. There was a greater risk of overall mortality (HR = 1.38, 95% CI = 1.14-1.67, P<.001) and cancer-specific mortality (HR = 1.92, 95% CI=1.49-2.47, P < .001) associated with IRI than with 5FU/LV. The superiority of OX on survival was found in participants aged 66 to 79 but not in those aged 80 and older. CONCLUSION: This "real world" comparative effectiveness research extends randomized controlled trial results by documenting the relative survival benefit of OX in older adults with Stage III colon cancer. The associated shift in treatment away from 5FU/LV alone or IRI toward OX is consistent with evidence-based medicine from real-world outcomes research.

Chemotherapy treatment and survival in older women with estrogen receptor-negative metastatic breast cancer: a population-based analysis.

UNLABELLED: To investigate the survival benefit associated with chemotherapy receipt in older women with estrogen receptor-negative (ER-) Stage IV breast cancer. DESIGN: Observational, retrospective cohort study using Cox proportional hazards regression to determine effect of chemotherapy on hazard of all-cause mortality. The two samples were an overall sample (n=1,519) and a propensity score-matched sample (n=580) to control for selection to treatment receipt. Hazard ratios (HRs) and 95% confidence intervals (CIs) were obtained for regression models. SETTING: U.S. women within the National Cancer Institute Surveillance, Epidemiology and End Results cancer registries (SEER) linked to Medicare enrollment and claims database. PARTICIPANTS: Female Medicare beneficiaries aged 66 and older with Stage IV ER- breast cancer diagnosed between 1999 and 2005. MEASUREMENTS: Outcome measure was all-cause death during the follow-up period. Survival was measured as time from breast cancer diagnosis until death or last follow-up date. Information on receipt of chemotherapy, defined as chemotherapy received within 6 months after diagnosis, was obtained from linked Medicare claims. RESULTS: One thousand five hundred nineteen ER- women diagnosed with metastatic breast cancer were identified; 494 (33%) received chemotherapy. Chemotherapy was associated with a statistically significant survival benefit (HR=0.61, 95% CI=0.54-0.70). Age did not modify the survival benefit of chemotherapy. CONCLUSION: Chemotherapy received within 6 months after diagnosis was associated with a 39% lower hazard of death within the time period for the study. These findings reflect chemotherapy use outside of the clinical trial setting and have important clinical and policy implications for the study of treatments in older women with advanced ER- breast cancer.