Trends in the Treatment of Metastatic Colon and Rectal Cancer in Elderly Patients.

BACKGROUND: Little is known about the use and costs of antineoplastic regimens for elderly patients with metastatic colorectal cancer (mCRC). We report population-based trends over a 10-year period in the treatment, survival, and costs in mCRC patients, stratified by ages 65-74 and 75+. METHODS: We used Surveillance, Epidemiology, and End Results-Medicare data for persons diagnosed with metastatic colon (N=16117) or rectal cancer (N=4008) between 2000 and 2009. We estimated the adjusted percent of patients who received antineoplastic agents, by type, number, and their costs 12 months following diagnosis. We report the percent of patients who received 3 or more of commonly prescribed agents and estimate survival for the 24-month period following diagnosis by age and treatment. RESULTS: The percentage that received 3 or more agents increased from 3% to 73% in colon patients aged 65-74 and from 2% to 53% in patients 75+. Similar increases were observed in rectal patients. Average 1-year costs per patient in 2009 were $106,461 and $102,680 for colon and rectal cancers, respectively, reflecting an increase of 32% and 20%, for patients who received antineoplastic agents. Median survival increased by about 6 and 10 months, respectively, for colon and rectal patients aged 65-74 who received antineoplastic agents, but an improvement of only 1 month of median survival was observed for patients 75+. CONCLUSIONS: Expensive multiple agent regimens are increasingly used in older mCRC patients. For patients aged 64-75 years, these treatments may be associated with several months of additional life, but patients aged 75+ may incur considerable expense without any survival benefit.

Sensitivity of Medicare claims data for measuring use of standard multiagent chemotherapy regimens.

PURPOSE: We sought to determine the accuracy with which Medicare billing data documents elderly Medicare cancer patients' receipt of common multiagent chemotherapy regimens. METHODS: We merged gold-standard clinical trial data from 406 elderly cancer patients known to be treated on 1 of 6 Cancer and Leukemia Group B (CALGB) breast, colorectal, and lung cancer trials (trial numbers; 9344, 9730, 9235,9732, 80203, 89803) with their Medicare claims data from Centers for Medicare and Medicaid Services (CMS). Comparing CMS chemotherapy codes to gold-standard CALGB treatment data, we estimated Medicare data's sensitivity at measuring the correct drugs and schedule for each of the multiagent chemotherapy regimens. RESULTS: Overall 92% (375/406) of CALGB patients had contemporaneous CMS claims indicating receipt of chemotherapy. The overall sensitivity of CMS ambulatory claims for documenting treatment with the correct drugs and on the correct schedule (ie, all drugs had to be billed on the same day) for the 5 common multiagent chemotherapy regimens was 78% (275/354) for those potentially treated in the ambulatory setting. The sensitivity was similar for all treatment regimens: carboplatin and paclitaxel 83%, 5-fluorouracil and leucovorin 80%, fluorouracil, leucovorin, and irinotecan (FOLFIRI) 76%, doxorubicin and cyclophosphamide 75%, and cisplatin and etoposide 75%. CONCLUSIONS: We correctly identified at least 3-quarters of elderly Medicare cancer patients treated on a clinical trial with standard first-line multiagent chemotherapy regimens in the ambulatory setting by applying coding algorithms to their CMS claims. The algorithms may be useful in identifying cohorts of elderly Medicare patients for observational studies of the comparative effectiveness of standard multiagent chemotherapy regimens.

Elderly breast and colorectal cancer patients' clinical course: patient and contextual influences.

BACKGROUND: The social and medical environments that surround people are each independently associated with their cancer course. The extent to which these characteristics may together mediate patients' cancer care and outcomes is not known. METHODS: Using multilevel methods and data, we studied elderly breast and colorectal cancer patients (level I) within urban social (level II: ZIP code tabulation area) and health care (level III: hospital service area) contexts. We sought to determine (1) which, if any, observable social and medical contextual attributes were associated with patient cancer outcomes after controlling for observable patient attributes, and (2) the magnitude of residual variation in patient cancer outcomes at each level. RESULTS: Numerous patient attributes and social area attributes, including poverty, were associated with unfavorable patient cancer outcomes across the full clinical cancer continuum for both cancers. Health care area attributes were not associated with patient cancer outcomes. After controlling for observable covariates at all 3 levels, there was substantial residual variation in patient cancer outcomes at all levels. CONCLUSIONS: After controlling for patient attributes known to confer risk of poor cancer outcomes, we find that neighborhood socioeconomic disadvantage exerts an independent and deleterious effect on residents' cancer outcomes, but the area supply of the specific types of health care studied do not. Multilevel interventions targeted at cancer patients and their social areas may be useful. We also show substantial residual variation in patient outcomes across social and health care areas, a finding potentially relevant to traditional small area variation research methods.

Predictors of newly diagnosed cancer patients' understanding of the goals of their care at initiation of chemotherapy.

BACKGROUND: The American Society of Clinical Oncology Quality Oncology Practice Initiative endorses in their core measures that providers should discuss the goals of care (GOC) at the time of chemotherapy consent. GOC refers to chemotherapy treatment intent: cure versus noncure. In this study, the authors sought to determine whether attributes of patients and initial patient-physician encounters were associated with patients' understanding of their GOC. METHODS: In total, the authors surveyed 125 consecutive, newly diagnosed patients who were receiving chemotherapy for solid malignancies at a single academic cancer center and performed a medical record review for additional data. Patient understanding of their oncologist's GOC and oncologist's reported GOC were compared. The primary outcome was concordance of patient-physician dyads regarding the GOC (cure vs noncure). RESULTS: One hundred twenty-five of 137 of eligible patients (91%) completed the survey. Only 95 of 125 patient-physician pairs (75%) patient-physician pairs were concordant regarding the GOC. In a multivariable logistic regression, both older patients (odds ratio, 0.21; 95% confidence interval, 0.08-0.57) and non-native English speakers had an almost 80% lower odds (odds ratio, 0.23; 95% confidence interval, 0.05-0.93) of GOC concordance compared with younger patients and native English speakers. Patients who received printed chemotherapy information during the patient-physician consent process had almost 3 times greater odds (odds ratio, 2.88; 95% confidence interval, 1.24-6.68) of GOC concordance with their physician compared with those who did not receive materials. CONCLUSIONS: Patient misunderstanding of GOC was substantial, with 25% of cancer patients misunderstanding the goal of their chemotherapy treatment. Key predictors of GOC misunderstanding included factors that potentially were amenable to interventions at the time of chemotherapy consent.

Historic Clinical Trial External Control Arm Provides Actionable GEN-1 Efficacy Estimate Before a Randomized Trial.

PURPOSE: To inform continued development of the novel immune agent GEN-1, we compared ovarian cancer patients' end points from a neoadjuvant single-arm phase IB study with those of similar historic clinical trial (HCT) patients who received standard neoadjuvant chemotherapy. METHODS: Applying OVATION-1 trial (ClinicalTrials.gov identifier: NCT02480374) inclusion and exclusion criteria to Medidata HCT data, we identified historical trial patients for comparison. Integrating patient-level Medidata historic trial data (N = 41) from distinct neoadjuvant ovarian phase I-III trials with patient-level OVATION-1 data (N = 18), we selected Medidata patients with similar baseline characteristics as OVATION-1 patients using propensity score methods to create an external control arm (ECA). RESULTS: Fifteen OVATION-1 patients (15 of 18, 83%) were matched to 15 (37%, 15 of 41) Medidata historical trial control patients. Matching attenuated preexisting differences in attributes between the groups. The median progression-free survival time was not reached by the OVATION-1 group and was 15.8 months (interquartile range, 11.40 months to nonestimable) for the ECA. The hazard of progression was 0.53 (95% CI, 0.16 to 1.73), favoring GEN-1 patients. Compared with ECA patients, OVATION-1 patients had more nausea, fatigue, chills, and infusion-related reactions. CONCLUSION: Comparing results of a single-arm early-phase trial to those of a rigorously matched HCT ECA yielded insights regarding comparative efficacy prior to a randomized controlled trial. The effect size estimate itself informed both the decision to continue development and the randomized phase II trial (ClinicalTrials.gov identifier: NCT03393884) sample size. The work illustrates the potential of HCT data to inform drug development.

Reasons for underuse of recommended therapies for colorectal and lung cancer in the Veterans Health Administration.

BACKGROUND: Many studies have documented low rates of effective cancer therapies, particularly in older or minority populations. However, little is known about why effective therapies are underused in these populations. METHODS: The authors examined medical records of 584 patients with cancer diagnosed or treated in Department of Veterans Affairs facilities to assess reasons for lack of 1) surgery for stage I/II nonsmall cell lung cancer, 2) surgery for stage I/II/III rectal cancer, 3) adjuvant radiation therapy for stage II/III rectal cancer, and 4) adjuvant chemotherapy for stage III colon cancer. They also assessed differences in reasons for underuse by patient age and race. RESULTS: Across the 4 guideline-recommended treatments, 92% to 99% of eligible patients were referred to the appropriate cancer specialist; however, therapy was recommended in only 74% to 92% of eligible cases. Poor health was cited in the medical record as the reason for lack of therapy in 15% to 61% of underuse cases; patient refusal explained 26% to 58% of underuse cases. African American patients were more likely to refuse surgery. Older patients were more likely to refuse treatments. CONCLUSIONS: Recommendation against therapy was a primary factor in underuse of effective therapies in older and sicker patients. Patients' refusal of therapy contributed to age and racial disparities in care. Improved data on the effectiveness of cancer therapies in community populations and interventions aimed at improved communication of known risks and benefits of therapy to cancer patients could be effective tools to reduce underuse and lingering disparities in care.

Improved outcomes associated with higher surgery rates for older patients with early stage nonsmall cell lung cancer.

BACKGROUND: Although surgery offers the greatest chance of a cure for patients with early stage nonsmall cell lung cancer (NSCLC), older and sicker patients often fail to undergo resection. The benefits of surgery in older patients and patients with multiple comorbidities are uncertain. METHODS: The authors identified a national cohort of 17,638 Medicare beneficiaries aged ≥66 years living in Surveillance, Epidemiology, and End Results (SEER) areas who were diagnosed with stage I or II NSCLC during 2001 to 2005. Areas with high and low rates of curative surgery for early stage lung cancer were compared to estimate the effectiveness of surgery in older and sicker patients. Logistic regression models were used to assess mortality according to the quintile of area-level surgery rates, adjusting for potential confounders. RESULTS: Less than 63% of patients underwent surgery in low-surgery areas, whereas >79% underwent surgery in high-surgery areas. High-surgery areas operated on more patients of advanced age and patients with chronic obstructive pulmonary disease than low-surgery areas. The adjusted all-cause 1 year mortality was 18% in high-surgery areas versus 22.8% in low-surgery areas (adjusted odds ratio [OR], 0.89; 95% confidence interval [CI], 0.86-0.93) for each 10% increase in the surgery rate).The 1-year lung-cancer-specific mortality similarly was lower in high-surgery areas (12%) versus low-surgery areas (16.9%; adjusted OR, 0.86; 95% CI, 0.82-0.91) for each 10% increase in the surgery rate. CONCLUSIONS: Higher rates of surgery for stage I/II NSCLC were associated with improved survival, even when older patients and sicker patients underwent resection. The authors concluded that more work is needed to identify and reduce barriers to surgery for early stage NSCLC.

Most colorectal cancer survivors live a large proportion of their remaining life in good health.

PURPOSE: Colorectal cancer (CRC) diagnosis reduces life expectancy and decreases patients' well-being. We sought to assess the determinants of health and functional status and estimate the proportion of remaining life that CRC survivors would spend in good health. METHODS: Using Sullivan method, healthy life expectancy was calculated based on survival data of 14,849 CRC survivors within a population-based cancer registry in southern Netherlands and quality of life information among a random sample of these survivors (n = 1,291). RESULTS: Overall, albeit short life expectancy (LE at age 50 = 12 years for males and 13 years for females), most CRC survivors spent a large proportion of their remaining life in good health (74 and 77 %, for males and females, respectively). Long-term survivors may expect to live a normal life span (LE at age 50 = 30 years) and spent a large proportion of the remaining life in good health (78 %). In distinction, those with stage IV CRC had less than 2 years to live and spent more than half of their remaining life in poor health. CONCLUSIONS: Most CRC patients may expect no compromise on living a healthy life, underlining the importance of early detection. On the other hand, the high proportion of non-healthy years among stage IV CRC survivors confirms the importance of early detection and palliative care.

Area-level variations in cancer care and outcomes.

BACKGROUND: : Substantial regional variations in health-care spending exist across the United States; yet, care and outcomes are not better in higher-spending areas. Most studies have focused on care in fee-for-service Medicare; whether spillover effects exist in settings without financial incentives for more care is unknown. OBJECTIVE: : We studied care for cancer patients in fee-for-service Medicare and the Veterans Health Administration (VA) to understand whether processes and outcomes of care vary with area-level Medicare spending. DESIGN: : An observational study using logistic regression to assess care by area-level measures of Medicare spending. SUBJECTS: : Patients with lung, colorectal, or prostate cancers diagnosed during 2001-2004 in Surveillance, Epidemiology, and End Results (SEER) areas or the VA. The SEER cohort included fee-for-service Medicare patients aged older than 65 years. MEASURES: : Recommended and preference-sensitive cancer care and mortality. RESULTS: : In fee-for-service Medicare, higher-spending areas had higher rates of recommended care (curative surgery and adjuvant chemotherapy for early-stage non-small-cell lung cancer and chemotherapy for stage III colon cancer) and preference-sensitive care (chemotherapy for stage IV lung and colon cancer and primary treatment of local/regional prostate cancer) and had lower lung cancer mortality. In the VA, we observed minimal variation in care by area-level Medicare spending. DISCUSSION: : Our findings suggest that intensity of care for Medicare beneficiaries is not driving variations in VA care, despite some overlap in physician networks. Although the Dartmouth Atlas work has been of unprecedented importance in demonstrating variations in Medicare spending, new measures may be needed to better understand variations in other populations.

Quality of care for older patients with cancer in the Veterans Health Administration versus the private sector: a cohort study.

BACKGROUND: The Veterans Health Administration (VHA) is the largest integrated health care system in the United States. Studies suggest that the VHA provides better preventive care and care for some chronic illnesses than does the private sector. OBJECTIVE: To assess the quality of cancer care for older patients provided by the VHA versus fee-for-service Medicare. DESIGN: Observational study of patients with cancer that was diagnosed between 2001 and 2004 who were followed through 2005. SETTING: VHA and non-VHA hospitals and office-based practices. PATIENTS: Men older than 65 years with incident colorectal, lung, or prostate cancer; lymphoma; or multiple myeloma. MEASUREMENTS: Rates of processes of care for colorectal, lung, or prostate cancer; lymphoma; or multiple myeloma. Rates were adjusted by using propensity score weighting. RESULTS: Compared with the fee-for-service Medicare population, the VHA population received diagnoses of colon (P < 0.001) and rectal (P = 0.007) cancer at earlier stages and had higher adjusted rates of curative surgery for colon cancer (92.7% vs. 90.5%; P < 0.010), standard chemotherapy for diffuse large B-cell non-Hodgkin lymphoma (71.1% vs. 59.3%; P < 0.001), and bisphosphonate therapy for multiple myeloma (62.1% vs. 50.4%; P < 0.001). The VHA population had lower adjusted rates of 3-dimensional conformal or intensity-modulated radiation therapy for prostate cancer treated with external-beam radiation therapy (61.6% vs. 86.0%; P < 0.001). Adjusted rates were similar for 9 other measures. Sensitivity analyses suggest that if patients with cancer in the VHA system have more severe comorbid illness than other patients, rates for most indicators would be higher in the VHA population than in the fee-for-service Medicare population. LIMITATION: This study included only older men and did not include information about performance status, severity of comorbid illness, or patient preferences. CONCLUSION: Care for older men with cancer in the VHA system was generally similar to or better than care for fee-for-service Medicare beneficiaries, although adoption of some expensive new technologies may be delayed in the VHA system. PRIMARY FUNDING SOURCE: Department of Veterans Affairs.

Introduction to the medical professions through an innovative medical student-run pipeline program.

Underrepresented minorities (URMs) make up a disproportionately small percentage of medical school applicants, matriculants, and physicians relative to the general US population. Preprofessional pipeline programs may help introduce URMs to careers in the medical field. MiniMeds was developed as a paracurricular enrichment program that targeted URM students. The curriculum was designed and administered by medical students, and 2 trials of this program were conducted. Data were collected pre and post program through a survey that assessed knowledge of medical concepts and knowledge of and interest in careers in medicine. Attendance at program sessions correlated with baseline knowledge about medical professions. Knowledge about medical concepts increased significantly from baseline to follow-up for boys, a group significantly represented by URMs in our cohort. Median scores for knowledge of medical careers increased significantly from baseline to followup for URMs as well as for boys and girls. Preprofessional pipeline programs such as MiniMeds are able to engage and develop medical knowledge in URM students at a critical developmental age. Further evaluation and implementation of programs that incorporate medical students to actively develop and lead pipeline programs are warranted.

Associations Between Amplification (1q) and Prior Cancer in a Real-World De Novo Myeloma Cohort.

Genomic biomarkers inform treatment in multiple myeloma (MM), making patient clinical data a potential window into MM biology. We evaluated de novo MM patients for associations between specific MM cytogenetic patterns and prior cancer history. Analyzing a MM real-world dataset, we identified a cohort of 1769 patients with fluorescent in situ hybridization cytogenetic testing at diagnosis. Of the patients, 241 (0.14) had histories of prior cancer(s). Amplification of the long arm of chromosome 1 [amp(1q)] varied by prior cancer history (0.31 with prior cancer vs 0.24 without; 2-sided P = .02). No other MM translocations, amplifications, or deletions were associated with prior cancers. Amp(1q) and cancer history remained strongly associated in a logistic regression adjusting for patient demographic and disease attributes. The results merit follow-up regarding carcinogenic treatment effects and screening strategies for second malignancies. Broadly, the findings suggest that analyses of patient-level phenotypic-genomic real-world dataset may accelerate cancer research through hypothesis-generating studies.

Utility of administrative claims data for the study of brain metastases: a validation study.

In this study, we sought to determine the accuracy with which the International Classification of Diseases, 9th Edition, Clinical Modification (ICD-9-CM) diagnosis code for "secondary neoplasm of brain and spinal cord" in health insurance claims measures clinically evident central nervous system (CNS) metastases in patients with non-small cell lung cancer (NSCLC). For 241 consecutive patients with newly diagnosed NSCLC, we compared ICD-9-CM "secondary neoplasm" codes indicating tumor spread to the CNS from institutional billing records to gold-standard chart review to determine: (1) sensitivity, specificity and positive predictive value (PPV) of the site-specific secondary neoplasm code and (2) the accuracy in time of its appearance within billing records compared with the gold standard date of CNS relapse. The occurrence of at least one ICD-9-CM code for brain metastasis (Algorithm 1) had a sensitivity of 100% (95% CI: 100-100%) and PPV of 91% (95% CI: 87-94%). By requiring >or= 2 codes (Algorithm 2) or >or= 3 codes (Algorithm 3) for the diagnosis of brain metastasis in claims, specificity and PPV improved, while sensitivity did not drop substantially. The claims-based date of diagnosis was also accurate, with 92% of dates falling within 30 days of the gold standard. ICD-9-CM codes in institutional billing claims reliably documented NSCLC metastases to the CNS. These results suggest that Medicare claims data may be used to evaluate clinical and epidemiological issues related to brain metastases in elderly cancer patients.

Nucleus-specific importin alpha proteins and nucleoporins regulate protein import and nuclear division in the binucleate Tetrahymena thermophila.

The ciliate Tetrahymena thermophila, having both germ line micronuclei and somatic macronuclei, must possess a specialized nucleocytoplasmic transport system to import proteins into the correct nucleus. To understand how Tetrahymena can target proteins to distinct nuclei, we first characterized FG repeat-containing nucleoporins and found that micro- and macronuclei utilize unique subsets of these proteins. This finding implicates these proteins in the differential permeability of the two nuclei and implies that nuclear pores with discrete specificities are assembled within a single cell. To identify the import machineries that interact with these different pores, we characterized the large families of karyopherin homologs encoded within the genome. Localization studies of 13 putative importin (imp) alpha- and 11 imp beta-like proteins revealed that imp alpha-like proteins are nucleus specific--nine localized to the germ line micronucleus--but that most imp beta-like proteins localized to both types of nuclei. These data suggest that micronucleus-specific proteins are transported by specific imp alpha adapters. The different imp alpha proteins exhibit substantial sequence divergence and do not appear to be simply redundant in function. Disruption of the IMA10 gene encoding an imp alpha-like protein that accumulates in dividing micronuclei results in nuclear division defects and lethality. Thus, nucleus-specific protein import and nuclear function in Tetrahymena are regulated by diverse, specialized karyopherins.

NSAIDs and colorectal cancer risk: do administrative data support a chemopreventive effect?

BACKGROUND: Randomized trials show non-steroidal anti-inflammatory drugs (NSAIDs) reduce precancerous polyps. Observational studies of the NSAID aspirin (ASA) suggest that it reduces invasive colorectal cancer (CRC) incidence, but because ASA use may also be a marker for healthy behaviors, these studies may be subject to selection bias. We sought to estimate the effectiveness of NSAIDs in CRC prevention in the population of elderly Medicare beneficiaries, minimizing this selection bias. METHODS: With National Ambulatory Medical Care Survey data, we find that patients with a diagnosis of osteoarthritis (OA) are 4.4 times more likely to concurrently have NSAID use documented than patients without such a diagnosis. We use this figure to estimate the expected NSAID-mediated reduction in CRC risk associated with a diagnosis of OA. Using Survival Epidemiology and End-Results (SEER)-Medicare data, we compare cases of elderly Medicare beneficiaries diagnosed with CRC in 1995 to persons without CRC to determine if their odds of antecedent OA differ. RESULTS: We estimate the expected NSAID-mediated reduction in CRC associated with an OA diagnosis to be between 6 and 16% (i.e., RR, 0.84-0.94). In the SEER-Medicare data, we find that individuals with a diagnosis of OA in Medicare claims in the previous 3 years had 15% lower odds of being diagnosed with CRC than individuals whose claims did not reflect antecedent OA (OR 0.85, 95%CI 0.80-0.91). CONCLUSIONS: This case-control study finds that elderly Medicare beneficiaries with histories of OA have 15% lower odds of developing CRC. These results are consistent with a preventive role for NSAIDs in CRC among the elderly.

Cancer and leukemia group B cancer control and health outcomes committee: origins and accomplishments.

Cancer and Leukemia Group B (CALGB) has conducted protocols in cancer prevention and control, psycho-oncology, and health services for many years. Significant findings from the studies have emerged and have helped shape the practice of medicine and the direction of future research in these areas. This article describes the origins of the Cancer Control and Health Outcomes Committee within CALGB and briefly describes significant findings and future work. The success CALGB has had with psycho-oncology and health services research has paved the way for other cooperative groups to develop these modalities. Cancer control research is growing and continues to gather momentum. This type of research is integral to providing quality care to patients and healthy populations.

Medicare Beneficiaries With Advanced Lung Cancer Experience Diverse Patterns Of Care From Diagnosis To Death.

Characterizations of average end-of-life care for people with cancer can obscure important differences in patients' experiences. Using Medicare claims data for 14,257 patients diagnosed with extensive-stage small-cell lung cancer in the period 1995-2009, we used latent class analysis to identify classes of people with different care patterns. We characterized care trajectories from diagnosis to death using time spent in five care settings-home, hospital inpatient unit (acute), hospital intensive care unit (ICU), postacute skilled nursing facility, and hospice-and transitions across these settings. We identified four classes of patients: 66 percent spent the time primarily at home, 11 percent were primarily in hospice, 17 percent were largely in an acute setting, and 6 percent were largely in an ICU. Patients in these classes differed significantly in terms of baseline clinical characteristics, survival length, time spent in hospice, site of death, and spending. The findings show substantial heterogeneity in patterns of care for patients with advanced cancer, which should be accounted for in efforts to improve end-of-life care.

Imatinib mesylate in patients with adenoid cystic cancers of the salivary glands expressing c-kit: a Princess Margaret Hospital phase II consortium study.

PURPOSE: This study aimed to assess the antitumor activity of imatinib in adenoid cystic carcinoma (ACC) of the salivary gland expressing c-kit. A high level of c-kit expression has been identified in more than 90% of ACCs. Imatinib specifically inhibits autophosphorylation of the bcr-abl, platelet-derived growth factor receptor beta, and c-kit tyrosine kinases. PATIENTS AND METHODS: In a single-arm, two-stage, phase II clinical trial, adult patients with unresectable or metastatic ACC measurable by Response Evaluation Criteria in Solid Tumors Group criteria and expressing c-kit by immunohistochemistry were treated with imatinib 400 mg orally bid. Response was assessed every 8 weeks. RESULTS: Sixteen patients have been enrolled onto the study; 10 were female. Median age was 47 years (range, 31 to 69 years). Median Eastern Cooperative Oncology Group performance status was 1 (range, 0 to 2). Fourteen patients had lung metastases, 14 had prior radiotherapy, and six had prior chemotherapy. Toxicities occurring in at least 50% of patients included fatigue, nausea, vomiting, diarrhea, anorexia, edema, dyspnea, and/or headache, usually of mild to moderate severity. In 15 patients assessable for response, no objective responses have been observed. Nine patients had stable disease as best response. Six patients had progressive disease after two cycles. CONCLUSION: Because of the lack of activity, the study has been stopped after the first stage and additional evaluation of imatinib in this population is not warranted. Overexpression of wild-type c-kit was not sufficient for clinical benefit from imatinib in ACC. Accrual to this study was rapid for a relatively rare cancer, encouraging additional efforts to identify more effective systemic therapy for these patients.

Survival and Toxicity After Cisplatin Plus Etoposide Versus Carboplatin Plus Etoposide for Extensive-Stage Small-Cell Lung Cancer in Elderly Patients.

PURPOSE: Elderly patients with cancer are under-represented in clinical trials and risk greater toxicity from chemotherapy. These patients and their physicians need better evidence to decide among guideline-recommended regimens. We test whether patients with extensive-stage small-cell lung cancer (ES SCLC) have noninferior survival and less hospital-based health care after carboplatin/etoposide compared with cisplatin/etoposide. METHODS: We analyzed SEER-Medicare data for beneficiaries with ES SCLC diagnosed at age 67 years and older between 1995 and 2009. Among patients treated with first-line chemotherapy in the ambulatory setting, 831 received cisplatin/etoposide and 2,846 received carboplatin/etoposide. Propensity score matching (2:1 ratio) yielded 778 cisplatin/etoposide and 1,502 carboplatin/etoposide patients. RESULTS: Survival was nearly identical in the two groups: 35.7 weeks for cisplatin/etoposide and 35.9 weeks for carboplatin/etoposide. The hazard ratio of 1 (95% CI, 0.91 to 1.09) excluded our prespecified threshold, indicating noninferiority. Mortality at 6 months was indistinguishable: 35% for cisplatin/etoposide and 34% for carboplatin/etoposide. After carboplatin/etoposide, patients were less likely to be admitted to a hospital (80% v 86%, P < .001) and had fewer hospitalizations (median 1 v 2, odds ratio 0.76, 95% CI, 0.65 to 0.9), ED visits (median 1 v 2, odds ratio 0.82, 95% CI, 0.7 to 0.96), and ICU stays (median 0 v 0, odds ratio 0.82, 95% CI, 0.69 to 0.99). CONCLUSION: First-line carboplatin/etoposide is associated with similar survival and less subsequent hospital-based health care use than cisplatin/etoposide among elderly patients with ES SCLC treated in ambulatory settings.