Risk and Consequences of Chemotherapy-Induced Febrile Neutropenia in Patients With Metastatic Solid Tumors

Focus on Quality Original Contribution Risk and Consequences of Chemotherapy-Induced Febrile Neutropenia in Patients With Metastatic Solid Tumors By...
Author: Rodney Barker
3 downloads 0 Views 298KB Size
Focus on Quality

Original Contribution

Risk and Consequences of Chemotherapy-Induced Febrile Neutropenia in Patients With Metastatic Solid Tumors By Derek Weycker, PhD, Xiaoyan Li, PhD, John Edelsberg, MD, MPH, Rich Barron, MS, Alex Kartashov, PhD, Hairong Xu, MD, PhD, and Gary H. Lyman, MD, MPH Policy Analysis (PAI), Brookline, MA; Amgen, Thousand Oaks, CA; and Hutchinson Cancer Research Center, Seattle, WA

Abstract Purpose: Although studies have evaluated the risk and consequences of febrile neutropenia (FN) among patients receiving cancer chemotherapy in US clinical practice, none have focused on a broad group of patients with metastatic disease.

Methods: A retrospective cohort design and health care claims (2006 to 2011) from private health plans covering a geographically diverse US population of ⬎ 30 million persons annually were used. The study population included adults who underwent myelosuppressive chemotherapy for metastatic cancer of the breast (MBC), colon/rectum (MCRC), lung (MLC), ovaries (MOC), or prostate (MPC). For each patient, the first chemotherapy course and each cycle therein, along with each episode of FN and the consequences thereof, were identified.

Results: The most common regimens, by cancer type, were paclitaxel (18% of 15,318 patients with MBC); oxalipla-

Introduction Neutropenia is a common adverse effect of myelosuppressive chemotherapy. Neutropenia increases the risk of infection, which is typically signaled by fever. When neutropenic patients develop fever (ie, febrile neutropenia [FN]), the likelihood of infection and serious consequences often necessitates hospitalization for urgent evaluation, ongoing monitoring, and administration of intravenous (IV) antibiotics.1,2 FN, as well as severe or prolonged neutropenia, can lead to dose delays, dose reductions, and/or chemotherapy discontinuations, interfering with the delivery of optimal treatment.1,3-7 Although several studies have examined the risk of FN and associated economic consequences among patients with various types of cancers,2,4,8-13 in proportion to the prevalence of metastatic cancer, relatively little has been reported about the risk and consequences of FN for persons with metastatic cancer in clinical practice.14,15 The risk and consequences of FN may vary across cancer- and stage-specific subgroups because of systematic and important differences in patients, their characteristics, and their treatment.9,16 Patients with metastatic disease are typically older, have more comorbidities, and have poorer performance status than patients with less-severe disease. Treatment in the metastatic setting is often less aggressive, and alternative approaches to managing toxicities—such as the use of less myelosuppressive regimens or dose or schedule modifications in lieu of prophylaxis with colony-stimulating factor— Copyright © 2014 by American Society of Clinical Oncology

tin, fluorouracil, and leucovorin (23% of 16,923 patients with MCRC); carboplatin plus paclitaxel (23% of 21,999 patients with MLC); carboplatin plus paclitaxel (49% of 7,433 patients with MOC); and docetaxel (68% of 4,667 patients with MPC). Across cancers, FN occurred in 13.1% to 20.6% of patients during their chemotherapy course, most often required hospitalization (89% to 94%), and most often occurred in the first cycle (23% to 36%). Among hospitalized patients with FN, mean length of stay ranged from 7.0 to 7.5 days, and inpatient mortality ranged from 3.9% to 10.3%; mean FNrelated costs during the cycle ranged from $16,291 to $19,456.

Conclusion: Among patients receiving myelosuppressive chemotherapy for metastatic cancer in US clinical practice, FN is a frequent complication, associated with significant morbidity, mortality, and economic costs, and should be given careful consideration in the treatment of this population.

have been recommended in recent literature, especially when the intent of such care is palliative.17-27 Moreover, although some evidence on the risk and consequences of FN is available from randomized controlled trials, evidence from the study setting is not often reflective of clinical practice, particularly in the metastatic setting.28 For all of these reasons, a closer examination of the risk and consequences of FN among patients with metastatic disease in clinical practice is warranted. One source of data on the real-world complications of patients with metastatic cancer receiving myelosuppressive chemotherapy is health care claims databases. Although lacking clinical richness, such databases provide access to the health care experiences (across continuum of care settings) of tens of millions of persons over a multiyear period of time and thus contain information on large numbers of patients with specific cancer diagnoses who are treated with specific chemotherapy regimens. A specific diagnostic code for FN is not available in health care claims databases; however, an operational algorithm including a combination of codes for neutropenia, fever, and infection may be used to estimate the risk and consequences of FN.14,29,30

Methods Study Design and Data Source A retrospective cohort design and data from two large integrated health care claims repositories were employed. The two

J A N U A R Y 2015



jop.ascopubs.org

Downloaded from ascopubs.org by 37.44.207.184 on January 16, 2017 from 037.044.207.184 Copyright © 2017 American Society of Clinical Oncology. All rights reserved.

47

Weycker et al

repositories—the Truven Health Analytics MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits Databases and the IMS LifeLink PharMetrics Health Plan Claims Database— both comprise medical (ie, facility and professional services) and outpatient pharmacy claims from a large number of participating private health plans. Data for our study spanned the period from July 1, 2006, through December 31, 2011. Use of the study databases for health services research is fully compliant with the Health Insurance Portability and Accountability Act Privacy Rule and the federal guidance on Public Welfare and the Protection of Human Subjects.31

Study Population The study population comprised all patients age ⱖ 18 years who, between January 1, 2007, and June 30, 2011, initiated myelosuppressive chemotherapy for metastatic cancer in one of five major solid tumors (breast [MBC], colorectal [MCRC], lung [MLC], ovarian [MOC], and prostate [MPC]). These tumors were selected because they are common and are often treated with myelosuppressive chemotherapy in US clinical practice. Presence of metastatic cancer was ascertained on the basis of the following: ⱖ one inpatient or ⱖ two outpatient encounters, at least 30 days apart, with a diagnosis code for cancer of the breast, colon/rectum, lung, ovaries, or prostate, or ⱖ one inpatient or ⱖ two outpatient encounters, at least 30 days apart, with a diagnosis of distant secondary malignant neoplasm at a site other than that of the primary cancer at any time on or after the date of the first encounter with a diagnosis of the primary cancer. Chemotherapy was ascertained at any time on or after the date of the first encounter with a diagnosis of distant secondary malignant neoplasm, or no earlier than 45 days before this date, based on ⱖ one medical claim for a chemotherapy drug or administration. For each patient with cancer receiving chemotherapy, each unique chemotherapy cycle within the first chemotherapy course was identified. The first cycle was defined as beginning with the date of chemotherapy initiation and ending with the first service date for the next administration of chemotherapy occurring ⱖ 7 days but ⬍ 59 days after the date of chemotherapy initiation. If a second cycle did not commence before day 60, both the first cycle and the course were considered to have been completed 30 days after the beginning of the cycle; if a second cycle did commence before day 60, but it included a new myelosuppressive agent, the first cycle and course were considered to have been completed on the date of the switch.14 The second and all subsequent cycles were similarly defined. Chemotherapy regimens were ascertained based on medical claims for antineoplastic agents with service dates within 6 days of cycle start. Regimens were categorized based on the specific combination of agents during the course as well as cycle periodicity. Patients were excluded from the study population if they had multiple primary cancers, received only nonmyelosuppressive chemotherapy, had any gaps in health care coverage during the 48

JOURNAL

OF

ONCOLOGY PRACTICE



6-month (ie, pretreatment) period, underwent hematopoietic stem-cell or bone marrow transplantation before or during chemotherapy, or had claims for chemotherapy administration only. A complete description of methods used to identify study participants and metastatic cancer and to characterize chemotherapy courses, cycles, and regimens can be found in the Data Supplement.

Study Measures FN episodes. FN was ascertained on a cycle-specific basis, from day 6 of the chemotherapy cycle (ie, beginning on sixth day after administration of first chemotherapy agent during that cycle) to the last day of the chemotherapy cycle. (First 5 days of cycle were excluded from follow-up, because chemotherapyinduced FN is unlikely to occur during this period.) FN was identified based on diagnosis codes for neutropenia (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 288.0), infections (Data Supplement), and fever (ICD-9-CM code 780.6); the presence of any of these codes (ie, those for neutropenia, infection, or fever), per the algorithms set forth in our article, was considered evidence of FN. A narrower definition, using only the diagnosis code for neutropenia, was also considered in sensitivity analyses. Hospitalized FN was identified based on acute-care facility admissions with a corresponding principal or secondary diagnosis. Outpatient FN was ascertained based on encounters in an ambulatory setting (eg, physician’s office, emergency department) with a corresponding diagnosis and, on the same date, an HCPCS Level I (ie, Common Procedural Terminology) code for IV administration of antimicrobial therapy. Such encounters that preceded or followed a hospitalization during the same cycle of chemotherapy were not considered as separate outpatient FN episodes. FN consequences. Clinical outcomes and health care costs of FN were characterized based on the setting of care. For hospitalized FN, clinical outcomes and health care costs were characterized in terms of the following: all-cause inpatient mortality (ie, death resulting from any reason while hospitalized), total hospital length of stay (ie, number of days hospitalized, from admission to discharge [inclusive]), total inpatient cost (ie, costs incurred while hospitalized), total FN-related outpatient cost incurred within the same cycle (but not before cycle day 6), and total overall cost (ie, total inpatient plus total FN-related outpatient costs). For FN treated on an outpatient basis, health care costs were characterized in terms of total FN-related outpatient cost from the date of the event through the end of the cycle. FN-related outpatient costs comprised encounters with a diagnosis of neutropenia, fever, or infection, as well as use of or prescriptions for colony-stimulating factors and antimicrobials (excluding colony-stimulating factor and antimicrobial prophylaxis). Health care costs were estimated using amounts paid (ie, expenditures) by health plans and patients to health care providers for services rendered and were expressed in 2011 US dollars by

V O L . 11, I S S U E 1

Copyright © 2014 by American Society of Clinical Oncology

Downloaded from ascopubs.org by 37.44.207.184 on January 16, 2017 from 037.044.207.184 Copyright © 2017 American Society of Clinical Oncology. All rights reserved.

Febrile Neutropenia in Metastatic Cancer

inflating values from prior years based on the medical care component of the US consumer price index for all urban consumers.

Characteristics of Patients and Supportive Care Patient characteristics were assessed from the beginning of the 6-month pretreatment period to the first day of the chemotherapy course and included the following: age; sex; presence of selected chronic comorbidities; history of blood disorders (anemia, neutropenia, other), infection, hospitalization (all cause and FN related), chemotherapy, and radiation therapy; pretreatment total health care cost (proxy for health status); and calendar year of chemotherapy initiation. Use of colony-stimulating factor (eg, filgrastim, pegfilgrastim, and sargramostim) and antimicrobials was characterized in terms of the reason for administration (primary v secondary prophylaxis). Use of radiation therapy during the chemotherapy course was examined. A detailed description of methods used to characterize these variables can be found in the Data Supplement.

Statistical Analyses Crude risk (ie, incidence proportion) of FN was summarized for each tumor- and regimen-specific subgroup using proportions and corresponding 95% CIs, which were generated using the Wilson score interval method. Hospitalized and outpatient FN were examined collectively and individually, during the chemotherapy course as well as on a cycle-specific basis. Clinical outcomes and health care costs of FN were summarized among the subgroups that developed this condition, on an episode-specific basis, for each tumor-specific subgroup using means (medians), percentages, and corresponding 95% CIs. For mortality, CIs were computed using the Wilson score interval; for outpatient encounters, hospital length of stay, and economic costs, CIs were computed using nonparametric bootstrapping (percentile method) from the study population (1,000 replicates with replacement). CIs were estimated assuming independence among observations. In analyses of clinical outcomes and health care costs of FN, patients with missing or invalid financial data were excluded.

Results Study findings, including treatment characteristics, FN risk, and FN consequences, for tumor-specific subgroups on an overall basis are described here and listed in Tables 1, 2, and 3; FN risk for the most common chemotherapy regimens, by tumor type, are also summarized in these tables. Patient characteristics are listed in the Appendix Table A1 (online only). Patient numbers, treatment characteristics,, and FN risk (including that based on narrower definition) for all tumor and regimen combinations—limited to those including ⱖ 100 patients— can be found in the Data Supplement. FN consequences based on the narrower definition and FN risk and consequences stratified by patient age are also provided in the Data Supplement. Copyright © 2014 by American Society of Clinical Oncology

Patient Characteristics Among the ⬎ 115,000 patients who received myelosuppressive chemotherapy for one of the metastatic solid tumors of interest, 15,309 with MBC, 21,994 with MLC, 16,934 with MCRC, 7,435 with MOC, and 4,668 with MPC met all other entry criteria (Data Supplement). Mean (⫾ standard deviation [SD]) age of patients ranged from 58 (⫹ 12) years for MBC to 70 (⫾ 10) years for MPC (Appendix Table A1, online only). The prevalence of chronic comorbidities was greatest in patients with MLC and MPC—the two oldest cohorts. A history of hospitalization during the 6-month pretreatment period ranged from 34% (MPC) to 79% (MOC). Bone was the most common site of metastasis in MBC, MLC, and MPC, whereas the liver and peritoneum were the most common sites in MCRC and MOC, respectively.

Treatment and Supportive Care The number of unique chemotherapy regimens, based on agents received in cycle one, administered to ⱖ 100 patients with metastatic solid tumors totaled 25 for MBC, 26 for MLC, 19 for MCRC, 10 for MOC, and four for MPC. The most frequently observed regimen was paclitaxel for MBC (18%); carboplatin plus paclitaxel for MLC (23%); oxaliplatin, fluorouracil, and leucovorin for MCRC (23%); carboplatin plus paclitaxel for MOC (49%); and docetaxel for MPC (68%). Mean (⫾ SD) duration of chemotherapy for metastatic solid tumors, on an overall basis, ranged from 98 (⫾ 74) days (with 5.0 [⫾ 4.8] cycles) for patients with MLC to 140 (⫾ 106) days (with 8.1 [⫾ 6.9] cycles) for patients with MCRC and varied widely among the different regimens for each cancer type (Table 1). The percentage of patients who received primary prophylaxis with a colony-stimulating factor ranged from 10% (MCRC) to 22% (MLC), whereas use of antimicrobial primary prophylaxis ranged from 6% (MCRC) to 8% (MLC).

FN Risk and Consequences The percentage of patients who experienced FN during their chemotherapy course ranged from 13% (95% CI, 12.3 to 13.9) for those with MOC to 21% (95% CI, 20.1 to 21.2) for those with MLC (Table 2). FN most often occurred in the first cycle, ranging from 23% of all episodes for MCRC to 36% for MLC; hospitalized FN accounted for 89% (MBC) to 94% (MLC) of all episodes. Mean length of stay with hospitalized FN ranged from 7.0 days (median, 5; 95% CI, 6.7 to 7.3) for MBC to 7.5 days (median, 5; 95% CI, 7.2 to 7.8) for MCRC (Table 3). Hospital mortality ranged from 3.9% (95% CI, 1.9 to 5.8) for MOC to 10.3% (95% CI, 8.8 to 11.8) for MLC. Among hospitalized patients with FN, associated total cost ranged from $16,291 (median, $8,157; 95% CI, 14,544 to 18,207) for MPC to $19,456 (median, $10,308; 95% CI, 17,294 to 21,829) for MOC. Total FN-related cost among those with outpatient FN ranged from $1,550 (median, $665; 95% CI, 1,305 to 1,846) for MLC to $1,769 (median, $554; 95% CI, 1,154 to 2,515) for MPC.

J A N U A R Y 2015



jop.ascopubs.org

Downloaded from ascopubs.org by 37.44.207.184 on January 16, 2017 from 037.044.207.184 Copyright © 2017 American Society of Clinical Oncology. All rights reserved.

49

Weycker et al

Table 1. Characteristics of Chemotherapy Courses Among Patients With Metastatic Solid Tumors Chemotherapy Course

No. of Days Tumor Type and Regimen

Mean

SD

Use of CSF/AMB Prophylaxis (%)†

Cycle Periodicity (%)*

No. of Cycles

Primary

Secondary

Every Week

Every 2 Weeks

Every 3 Weeks

Every 4 Weeks

CSF

AMB

CSF

AMB

Use of RT (%)

21.9

Mean

SD

Overall (n ⫽ 15,309)

135.9

113.1

9.3

9.8

43.5

13.3

24.9

18.3

16.7

7.1

13.2

5.8

Paclitaxel (n ⫽ 2,726)

157.3

129.3

12.5

11.7

65.9

10.9

11.0

12.3

4.6

6.3

7.6

5.8

20.8

Bevacizumab plus paclitaxel (n ⫽ 1,726)

175.8

123.1

14.1

11.0

70.7

13.0

8.1

8.3

3.9

7.1

9.6

6.9

14.4

Docetaxel (n ⫽ 1,012)

138.2

122.9

8.3

9.1

32.4

5.0

43.6

19.0

19.0

6.1

14.9

5.9

18.8

Gemcitabine (n ⫽ 888)

108.0

102.4

7.8

8.2

58.2

20.8

5.9

15.1

3.6

6.5

9.4

5.5

21.6

71.2

34.2

3.6

1.8

1.0

47.2

32.6

19.2

65.6

7.6

23.6

6.8

24.5

Overall (n ⫽ 21,994)

97.7

73.7

5.0

4.8

24.9

5.0

44.3

25.8

21.9

8.4

18.9

6.0

37.8

Carboplatin plus paclitaxel (n ⫽ 5,037)

93.7

59.6

5.4

4.7

34.5

5.9

38.8

20.8

18.7

8.4

15.6

6.4

49.0

Carboplatin plus etoposide (n ⫽ 2,530)

105.5

54.3

4.2

2.3

1.0

0.5

62.2

36.3

42.5

9.8

32.5

5.8

38.9

Pemetrexed (n ⫽ 1,580)

107.9

106.8

4.6

5.4

0.2

0.4

65.8

33.6

10.7

7.2

9.3

4.9

25.0

86.3

45.3

3.7

2.1

16.6

0.3

52.5

30.6

28.1

9.9

30.1

6.4

55.8

109.1

62.2

5.6

5.1

17.5

2.2

59.4

20.9

31.5

7.0

17.7

5.9

30.2

Overall (n ⫽ 16,934)

140.3

105.6

8.1

6.9

10.5

59.5

14.0

16.0

9.5

5.7

13.9

4.6

10.0

Fluorouracil, leucovorin, and oxaliplatin (n ⫽ 3,957)

155.8

97.7

9.1

6.2

2.7

80.5

7.7

9.2

10.4

6.0

16.3

4.1

7.2

Bevacizumab, fluorouracil, leucovorin, and oxaliplatin (n ⫽ 2,741)

160.3

103.6

9.3

6.6

2.3

80.9

7.3

9.5

11.6

6.3

16.2

4.1

6.4

Fluorouracil (n ⫽ 1,419)

111.4

101.6

6.5

6.1

21.4

53.3

7.0

18.3

1.6

4.7

1.3

4.2

27.9

Bevacizumab, fluorouracil, irinotecan, and leucovorin (n ⫽ 1,378)

175.4

127.8

10.4

8.4

6.7

71.6

10.2

11.5

13.6

4.8

16.4

4.6

6.6

Fluorouracil, irinotecan, and leucovorin (n ⫽ 1,078)

173.3

129.4

10.2

8.3

6.5

68.0

10.9

14.7

13.4

5.7

18.2

5.2

6.4

Overall (n ⫽ 7,435)

117.9

78.6

6.0

5.0

22.1

4.7

46.5

26.7

21.5

6.1

20.9

4.4

3.0

Carboplatin plus paclitaxel (n ⫽ 3,660)

129.9

76.9

6.2

4.8

11.0

2.1

66.5

20.3

24.6

6.9

21.7

4.2

1.8

Overall (n ⫽ 4,668)

131.8

101.0

7.0

6.8

22.3

6.1

49.1

22.5

17.8

6.6

15.6

4.8

18.6

Docetaxel (n ⫽ 3,192)

145.8

105.8

7.7

7.2

19.6

3.3

57.7

19.5

17.4

5.7

15.8

4.6

16.4

Metastatic breast cancer

Cyclophosphamide plus doxorubicin (n ⫽ 812) Metastatic lung cancer

Cisplatin plus etoposide (n ⫽ 1,508) Bevacizumab, carboplatin, and paclitaxel (n ⫽ 1,425) Metastatic colorectal cancer

Metastatic ovarian cancer

Metastatic prostate cancer

Abbreviations: AMB, antimicrobial; CSF, colony-stimulating factor; RT, radiotherapy; SD, standard deviation. * Based on duration of cycle one. † Primary: first receipt on or before day 5 of cycle one; secondary: first receipt (as prophylaxis) on or before day 5 of cycle two.

Discussion Using data from two large private health care claims repositories, we examined the risk and consequences of FN among patients with five common types of metastatic cancer. We found that 13% to 21% of patients, depending on cancer type, experienced FN during their chemotherapy course, most commonly requiring inpatient care and most commonly occurring during the first cycle. We also found that among patients experiencing FN, the economic consequences were substantial, with associated costs ranging from $16,000 to $19,000 for the great majority of patients requiring inpatient care (approximately 90%). We note that the estimated cost of an FN episode may not reflect the full impact of this condition, because patients 50

JOURNAL

OF

ONCOLOGY PRACTICE



who develop FN in one cycle have been found to be at elevated risk of FN in subsequent cycles, and costs occurring in subsequent cycles that might be related to the initial episode (eg, subsequent use of colony-stimulating factor or antimicrobial prophylaxis) were not captured in our study; such costs have been found to represent a substantial proportion of the total economic burden of FN.30 Other possible FN-related consequences that were not considered in our study include dose delays and reductions, early termination of planned chemotherapy, and increased antimicrobial use, all of which may lead to suboptimal patient outcomes. To our knowledge, our study is the largest and broadest evaluation to date of the risk and consequences of chemother-

V O L . 11, I S S U E 1

Copyright © 2014 by American Society of Clinical Oncology

Downloaded from ascopubs.org by 37.44.207.184 on January 16, 2017 from 037.044.207.184 Copyright © 2017 American Society of Clinical Oncology. All rights reserved.

Febrile Neutropenia in Metastatic Cancer

Table 2. Risk of FN Among Patients With Metastatic Solid Tumors Incidence of FN Chemotherapy Course Overall

Inpatient

Cycle One Outpatient

%

95% CI

%

95% CI

%

95% CI

Overall (n ⫽ 15,309)

15.8

15.2 to 16.4

14.0

13.4 to 14.5

2.3

2.1 to 2.6

Paclitaxel (n ⫽ 2,726)*

15.1

13.8 to 16.5

13.6

12.4 to 14.9

1.9

1.5 to 2.5

Bevacizumab plus paclitaxe l (n ⫽ 1,726)

16.8

15.1 to 18.6

14.6

13.0 to 16.4

2.8

Docetaxel (n ⫽ 1,012)*

21.5

19.1 to 24.1

19.3

17.0 to 21.9

Gemcitabine (n ⫽ 888)

15.3

13.0 to 17.8

13.9

11.8 to 16.3

Cyclophosphamide plus doxorubicin (n ⫽ 812)*

16.2

13.8 to 18.9

14.9

Overall (n ⫽ 21,994)

20.6

20.1 to 21.2

Carboplatin plus paclitaxel (n ⫽ 5,037)*

21.4

20.3 to 22.6

Carboplatin plus etoposide (n ⫽ 2,530)*

21.3

Pemetrexed (n ⫽ 1,580)

Overall

Outpatient

95% CI

%

95% CI

%

95% CI

4.0

3.7 to 4.3

3.6

3.4 to 4.0

0.4

0.3 to 0.5

2.5

2.0 to 3.2

2.3

1.8 to 3.0

0.2

0.1 to 0.4

2.1 to 3.7

2.4

1.8 to 3.3

2.2

1.6 to 3.0

0.2

0.1 to 0.6

3.5

2.5 to 4.8

6.2

4.9 to 7.9

5.3

4.1 to 6.9

0.9

0.5 to 1.7

1.7

1.0 to 2.8

2.1

1.4 to 3.3

1.8

1.1 to 2.9

0.3

0.1 to 1.0

12.6 to 17.5

2.1

1.3 to 3.3

7.1

5.6 to 9.1

6.5

5.0 to 8.4

0.6

0.3 to 1.4

19.3

18.8 to 19.8

1.7

1.6 to 1.9

7.4

7.1 to 7.7

7.0

6.6 to 7.3

0.4

0.4 to 0.5

20.4

19.3 to 21.5

1.6

1.3 to 2.0

6.7

6.1 to 7.4

6.4

5.7 to 7.1

0.3

0.2 to 0.5

19.7 to 22.9

19.4

17.9 to 21.0

2.3

1.8 to 3.0

10.1

9.0 to 11.3

9.3

8.2 to 10.4

0.8

0.5 to 1.3

23.4

21.4 to 25.6

22.3

20.3 to 24.4

1.6

1.1 to 2.4

10.0

8.6 to 11.5

9.3

8.0 to 10.8

0.7

0.4 to 1.2

Cisplatin plus etoposide (n ⫽ 1,508)*

20.8

18.8 to 22.9

19.4

17.5 to 21.5

1.8

1.2 to 2.6

9.5

8.1 to 11.0

9.0

7.7 to 10.5

0.5

0.2 to 1.0

Bevacizumab, carboplatin, and paclitaxel (n ⫽ 1,425)

20.6

18.6 to 22.8

19.1

17.1 to 21.2

2.1

1.5 to 3.0

6.6

5.4 to 8.0

6.4

5.2 to 7.8

0.2

0.1 to 0.6

Overall (n ⫽ 16,934)

13.7

13.2 to 14.2

12.4

11.9 to 12.9

1.7

1.5 to 1.9

3.1

2.9 to 3.4

2.8

2.6 to 3.1

0.3

0.2 to 0.4

Fluorouracil, leucovorin, and oxaliplatin (n ⫽ 3,957)*

13.4

12.4 to 14.5

12.0

11.0 to 13.1

1.8

1.4 to 2.3

2.5

2.1 to 3.0

2.3

1.9 to 2.8

0.2

0.1 to 0.4

Bevacizumab, fluorouracil, leucovorin, and oxaliplatin (n ⫽ 2,741)

11.8

10.7 to 13.1

10.6

9.6 to 11.8

2.0

1.6 to 2.6

2.4

1.9 to 3.1

2.0

1.6 to 2.6

0.4

0.2 to 0.7

Fluorouracil (n ⫽ 1,419)

11.6

10.0 to 13.4

11.0

9.5 to 12.8

0.6

0.3 to 1.1

2.2

1.5 to 3.1

2.2

1.5 to 3.1

0.0

0.0 to 0.0

Bevacizumab, fluorouracil, irinotecan, and leucovorin (n ⫽ 1,378)

13.3

11.6 to 15.2

12.1

10.5 to 13.9

1.7

1.1 to 2.5

1.9

1.3 to 2.8

Fluorouracil, irinotecan, and leucovorin (n ⫽ 1,078)

17.6

15.4 to 20.0

15.8

13.8 to 18.1

2.3

1.6 to 3.4

4.0

3.0 to 5.3

3.6

2.7 to 4.9

0.4

0.1 to 1.0

Overall (n ⫽ 7,435)

13.1

12.3 to 13.9

11.8

11.1 to 12.5

1.7

1.4 to 2.0

4.6

4.1 to 5.1

4.2

3.7 to 4.6

0.4

0.3 to 0.6

Carboplatin plus paclitaxel (n ⫽ 3,660)

12.2

11.1 to 13.3

10.7

9.8 to 11.8

1.9

1.5 to 2.3

4.1

3.5 to 4.8

3.9

3.3 to 4.5

0.3

0.1 to 0.5

Overall (n ⫽ 4,668)

17.7

16.6 to 18.8

16.4

15.4 to 17.5

1.8

1.4 to 2.2

5.3

4.7 to 6.0

4.9

4.3 to 5.6

0.4

0.3 to 0.6

Docetaxel (n ⫽ 3,192)

17.4

16.1 to 18.8

15.9

14.7 to 17.2

1.9

1.5 to 2.4

4.9

4.2 to 5.7

4.5

3.9 to 5.3

0.3

0.2 to 0.6

Tumor Type and Regimen

%

Inpatient

Metastatic breast cancer

Metastatic lung cancer

Metastatic colorectal cancer

1.7 (1.1, 2.5)

0.2 (0.1, 0.6)

Metastatic ovarian cancer

Metastatic prostate cancer

Abbreviation: FN, febrile neutropenia. * Regimens classified as intermediate risk for FN (10% to 20%) per National Comprehensive Cancer Network guidelines.32 Docetaxel plus paclitaxel administered every 3 weeks only; cyclophosphamide plus doxorubicin administered with sequential docetaxel.

apy-induced FN among patients with metastatic solid tumors in US clinical practice. Only two studies, to our knowledge, have evaluated in a detailed fashion the risk and consequences of FN among patients with metastatic cancer, and each of these studies was substantially smaller and focused on a single type of metastatic cancer (ie, breast and non–small-cell lung cancers).14,15 In addition, the study by Stokes et al15 was based on data that are now well over a decade old, and the study by Weycker et al14 was based on data from 2004 to 2008. Notwithstanding differences between the studies in their design, data sources, and methods of patient or patient case ascertainCopyright © 2014 by American Society of Clinical Oncology

ment, findings for those cancer types considered in our study and elsewhere were generally comparable. Although chemotherapy regimens listed in National Comprehensive Cancer Network guidelines as high risk (⬎ 20%) or intermediate risk for FN (10% to 20%) are identified in the tables, we note that estimated risks within tumor-, stage-, and regimen-specific subgroups may vary across settings (eg, clinical practice v clinical trials) because of systematic differences in patients and their treatments.28 We note several potential biases vis-á-vis patient (treatment) selection and outcome measurement that may affect the find-

J A N U A R Y 2015



jop.ascopubs.org

Downloaded from ascopubs.org by 37.44.207.184 on January 16, 2017 from 037.044.207.184 Copyright © 2017 American Society of Clinical Oncology. All rights reserved.

51

Weycker et al

Table 3. Clinical and Economic Consequences of FN Among Patients With Metastatic Solid Tumors* Breast Cancer FN Event

Mean

95% CI

Lung Cancer Mean

95% CI

Colorectal Cancer Mean

95% CI

Ovarian Cancer Mean

95% CI

Prostate Cancer Mean

95% CI

Requiring outpatient care only No. of events

316

No. of outpatient encounters

2.0

1.8 to 2.2

313 2.1

250

1.8 to 2.3

2.2

1.9 to 2.6

106 2.1

1.5 to 2.7

61 2.1

1.5 to 2.6

Cost, $ Total

1,569

1,358 to 1,796

1,550

1,305 to 1,846

1,578

1,314 to 1,870

1,593

1,205 to 2,011

1,769

1,154 to 2,515

Outpatient care

1,202

1,036 to 1,394

1,237

1,008 to 1,516

1,317

1,083 to 1,591

1,221

898 to 1,610

1,385

883 to 2,083

AMB

76

58 to 101

111

87 to 141

108

67 to 161

76

47 to 109

83

50 to 130

CSF

291

208 to 380

202

137 to 278

153

88 to 227

296

141 to 471

300

134 to 511

Requiring inpatient care No. of events

1,812

3,401

1,718

727

560

Hospital length of stay, days

7.0

6.7 to 7.3

7.0

6.8 to 7.2

7.5

7.2 to 7.8

7.5

6.9 to 8.1

7.2

6.7 to 7.8

Hospital mortality†

7.3

5.7 to 8.9

10.3

8.8 to 11.8

6.3

4.7 to 7.9

3.9

1.9 to 5.8

10.3

5.3 to 15.3

Cost, $ Total

17,271

16,006 to 18,604

17,119

16,377 to 17,974

19,178

17,949 to 20,481

19,456

17,294 to 21,829

16,291

14,544 to 18,207

Inpatient care

16,927

15,665 to 18,267

16,792

16,049 to 17,643

18,850

17,628 to 20,147

19,054

16,927 to 21,411

15,980

14,249 to 17,877

Outpatient care

99

73 to 127

72

56 to 91

119

80 to 171

105

71 to 146

84

AMB

72

60 to 86

71

63 to 79

68

55 to 82

70

52 to 92

65

38 to 146 49 to 85

CSF

173

142 to 205

183

156 to 211

142

111 to 171

227

164 to 299

161

111 to 218

Abbreviations: AMB, antimicrobial; CSF, colony-stimulating factor; FN, febrile neutropenia. * Results expressed per episode of FN. † Based on data from MarketScan only.33

ings of this study as well as important limitations. The accuracy of the algorithm for identifying patients receiving treatment for metastatic solid tumors is unknown, because it has not been validated. However, similar algorithms for identifying metastatic disease in health care claims database have been evaluated in formal validation studies and been found to have high (generally ⬎ 80%) positive predictive value.34,35 Because an ICD9-CM diagnosis code for FN (ie, neutropenia-related fever or infection) does not exist, an algorithm based on codes for neutropenia, fever, and infection (and IV antibiotic therapy for outpatient care) was employed to identify encounters for the events of interest. We note that in a recent study evaluating the accuracy of health care claims– based algorithms for identifying FN (ascertained from medical records), the true risk of FN was found to be lower than FN risk estimated using diagnosis codes for neutropenia, fever, and infection.29 Although it is possible that some infection-related encounters during a given cycle may not be related to FN— especially those that occur temporally distant (eg, 2 weeks)—it is likely that most are a consequence of treatment and associated neutropenia. For this reason, we also employed a narrower definition (which produced similar estimates of FN costs). In addition, these algorithms for identifying FN—as well as those used to characterize chemotherapy courses, cycles, and regimens— have been used in a number of studies published to date.14,30,36-41 Although our algorithm for ascertaining outpatient treatment of FN required the adminis52

JOURNAL

OF

ONCOLOGY PRACTICE



tration of IV antibiotic therapy, we acknowledge that some low-risk patients with FN may receive outpatient management with oral (rather than IV) antimicrobial therapy in clinical practice. To the extent that we missed such patients, we may have underestimated the frequency of outpatient FN and may have—to the extent these patients differ systematically in their economic profile from those with outpatient FN treated with IV agents—misestimated economic costs. Because some episodes of hospitalized FN were identified based on diagnosis codes in the secondary position, not all inpatient costs may be attributable to FN. Finally, our study sample comprised (principally) patients with cancer age ⬍ 65 years with private health plan coverage, and thus, the distribution of study participants by tumor type may not reflect clinical practice, and study results may not be generalizable to older patients. In summary, the results of this study suggest that the incidence of FN among patients with metastases from common cancers, along with the clinical and economic consequences of this condition, is considerable. Additional research is needed to identify subgroups of patients who are at particularly high FN risk so that they may be targeted for preventative measures. Acknowledgment Supported by Amgen funding to Policy Analysis. Presented in part at the 2013 San Antonio Breast Cancer Symposium, San Antonio, TX, December 10-14, 2013, and 55th Annual Meeting of the American Society of Hematology, New Orleans, LA, December 7-10, 2013.

V O L . 11, I S S U E 1

Copyright © 2014 by American Society of Clinical Oncology

Downloaded from ascopubs.org by 37.44.207.184 on January 16, 2017 from 037.044.207.184 Copyright © 2017 American Society of Clinical Oncology. All rights reserved.

Febrile Neutropenia in Metastatic Cancer

Authors’ Disclosures of Potential Conflicts of Interest Although all authors completed the disclosure declaration, the following author(s) and/or an author’s immediate family member(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a “U” are those for which no compensation was received; those relationships marked with a “C” were compensated. For a detailed description of the disclosure categories, or for more information about ASCO’s conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Employment or Leadership Position: Xiaoyan Li, Amgen (C); Rich Barron, Amgen (C); Hairong Xu, Amgen (C) Consultant or Advisory Role: None Stock Ownership: Xiaoyan Li, Amgen; Rich Barron, Amgen; Hairong Xu, Amgen Honoraria: None Research Funding: Derek Weycker, Amgen; John Edelsberg, Amgen; Alex Kartashov, Amgen; Gary H. Lyman, PI on research grant to Duke University Expert Testi-

mony: None Patents, Royalties, and Licenses: None Other Remuneration: None

Author Contributions Conception and design: Derek Weycker, Xiaoyan Li, John Edelsberg, Rich Barron, Hairong Xu, Gary H. Lyman Data analysis and interpretation: All authors Manuscript writing: All authors Final approval of manuscript: All authors Corresponding author: Derek Weycker, PhD, Policy Analysis (PAI), Four Davis Court, Brookline, MA 02445; e-mail: [email protected]

DOI: 10.1200/JOP.2014.001492; published online ahead of print at jop.ascopubs.org on December 9, 2014.

References 1. Smith TJ, Khatcheressian J, Lyman GH, et al: 2006 update of recommendations for the use of white blood cell growth factors: An evidence-based clinical practice guideline. J Clin Oncol 24:3187-3205, 2006

18. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Colon Cancer (version 3.2014). http://www.nccn.org/professionals/ physician_gls/pdf/colon.pdf

2. Caggiano V, Weiss RV, Rickert TS, et al: Incidence, cost and mortality of neutropenia hospitalization associated with chemotherapy. Cancer 103:19161924, 2005

19. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer (version 3.2014). http://www.nccn.org/ professionals/physician_gls/pdf/nscl.pdf

3. Lyman GH, Michels SL, Reynolds MW, et al: Risk of mortality in patients with cancer who experience febrile neutropenia. Cancer 116:5555-5563, 2010

20. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Ovarian Cancer (version 3.2014). http://www.nccn.org/professionals/physician_ gls/pdf/ovarian.pdf

4. Kuderer NM, Dale DC, Crawford J, et al: Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer 106:2258-2266, 2006 5. Bonadonna G, Moliterni A, Zambetti M, et al: 30 years’ follow up of randomised studies of adjuvant CMF in operable breast cancer: Cohort study. BMJ 330:217, 2005

21. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer (version 2.2014). http://www.nccn.org/professionals/physician_ gls/pdf/prostate.pdf 22. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Rectal Cancer (version 2.2014). http://www.nccn.org/professionals/ physician_gls/pdf/rectal.pdf

6. Lyman GH, Dale DC, Crawford J: Incidence and predictors of low doseintensity in adjuvant breast cancer chemotherapy: A nationwide study of community practices. J Clin Oncol 21:4524-4531, 2003

23. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Small Cell Lung Cancer (version 2.2014). http://www.nccn.org/ professionals/physician_gls/pdf/sclc.pdf

7. Kwak LW, Halpern J, Olshen RA, et al: Prognostic significance of actual dose intensity in diffuse large-cell lymphoma: Results of a tree-structured survival analysis. J Clin Oncol 8:963-977, 1990

24. Schnipper L, Smith T, Raghavan D, et al: American Society of Clinical Oncology identifies five key opportunities to improve care and reduce costs: The top five list for oncology. J Clin Oncol 30:1715-1724, 2012

8. Lyman GH, Kuderer N, Greene J, et al: The economics of febrile neutropenia: Implications for the use of colony-stimulating factors. Eur J Cancer 34:18571864, 1998

25. Smith T, Hillner B: A way forward on the medically appropriate use of white cell growth factors. J Clin Oncol 30:1584-1587, 2012

9. Schilling MB, Parks C, Deeter RG: Costs and outcomes associated with hospitalized cancer patients with neutropenic complications: A retrospective study. Exp Ther Med 2:859-866, 2011 10. Dulisse B, Li X, Gayle JA, et al: A retrospective study of the clinical and economic burden during hospitalizations among cancer patients with febrile neutropenia. J Med Econ 16:720-735, 2013 11. Bennett CL, Calhoun EA: Evaluating the total costs of chemotherapy-induced febrile neutropenia: Results from a pilot study with community oncology cancer patients. Oncologist 12:478-483, 2007 12. Calhoun EA, Brown S, Kozloff MS, et al: Uncompensated costs associated with the outpatient management of cancer chemotherapy-associated febrile neutropenia. Commun Oncol 2:293-296, 2005 13. Calhoun EA, Chang CH, Welshman EE, et al: Evaluating the total costs of chemotherapy-induced toxicity: Results from a pilot study with ovarian cancer patients. Oncologist 6:441-445, 2001 14. Weycker D, Edelsberg J, Kartashov A, et al: Risk and healthcare costs of chemotherapy-induced neutropenic complications in women with metastatic breast cancer. Chemotherapy 58:8-18, 2012 15. Stokes ME, Muehlenbein CE, Marciniak MD, et al: Neutropenia-related costs in patients with first-line chemotherapy for advanced non-small cell lung cancer. J Manag Care Pharm 15:669-682, 2009 16. Lyman GH, Abella E, Pettengell R: Risk factors for febrile neutropenia among patients with cancer receiving chemotherapy: A systematic review. Crit Rev Oncol Hematol 90:190-199, 2014 17. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Breast Cancer (version 3.2014). http://www.nccn.org/professionals/ physician_gls/pdf/breast.pdf

Copyright © 2014 by American Society of Clinical Oncology

26. Smith T, Hillner B: Bending the cost curve in cancer care. N Engl J Med 364:2060-2065, 2011 27. Bennett CL, Djulbegovic B, Norris LB, et al: Colony-stimulating factors for febrile neutropenia during cancer therapy. N Engl J Med 368:1131-1139, 2013 28. Kuderer NM, Wolff AC: Enhancing therapeutic decision making when options abound: Toxicities matter. J Clin Oncol 32:1990-1993, 2014 29. Weycker D, Sofrygin O, Seefeld K, et al: Technical evaluation of methods for identifying chemotherapy-induced febrile neutropenia in healthcare claims databases. BMC Health Serv Res 13:60, 2013 30. Weycker D, Malin J, Edelsberg J, et al: Cost of neutropenic complications of chemotherapy. Ann Oncol 19:454-460, 2008 31. US Department of Health and Human Services: Code of Federal Regulations: Title 45—Public Welfare: Part 46 —Protection of Human Subjects. http:// www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html 32. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Myeloid Growth Factors (version 2.2014). http://www.nccn.org/ professionals/physician_gls/pdf/myeloid_growth.pdf 33. Truven Health Analytics: MarketScan Research. https://marketscan.truven health.com/marketscanportal 34. Eichler AF, Lamont EB: Utility of administrative claims data for the study of brain metastases: A validation study. J Neurooncol 95:427-431, 2009 35. Nordstrom BL, Whyte JL, Stolar M, et al: Identification of metastatic cancer in claims data. Pharmacoepidemiol Drug Saf 21:21-28, 2012 (suppl 2) 36. Henk HJ, Becker L, Tan H, et al: Comparative effectiveness of pegfilgrastim, filgrastim, and sargramostim prophylaxis for neutropenia-related hospitalization: Two US retrospective claims analyses. J Med Econ 16:160-168, 2013 37. Naeim A, Henk HJ, Becker L, et al: Pegfilgrastim prophylaxis is associated with a lower risk of hospitalization of cancer patients than filgrastim prophylaxis: A

J A N U A R Y 2015



jop.ascopubs.org

Downloaded from ascopubs.org by 37.44.207.184 on January 16, 2017 from 037.044.207.184 Copyright © 2017 American Society of Clinical Oncology. All rights reserved.

53

Weycker et al

retrospective United States claims analysis of granulocyte colony-stimulating factors (G-CSF). BMC Cancer 13:11, 2013 38. Michels SL, Barron RL, Reynolds MW, et al: Costs associated with febrile neutropenia in the US. Pharmacoeconomics 30:809-823, 2012 39. Weycker D, Malin J, Kim J, et al: Risk of hospitalization for neutropenic complications of chemotherapy in patients with primary solid tumors receiving

pegfilgrastim or filgrastim prophylaxis: A retrospective cohort study. Clin Ther 31:1069-1081, 2009 40. Heaney ML, Toy EL, Vekeman F, et al: Comparison of hospitalization risk and associated costs among patients receiving sargramostim, filgrastim, and pegfilgrastim for chemotherapy-Induced neutropenia. Cancer 115:4839-4848, 2009 41. Chen-Hardee S, Chrischilles EA, Voelker MD, et al: Population-based assessment of hospitalizations for neutropenia from chemotherapy in older adults with non-Hodgkin’s lymphoma. Cancer Causes Control 17:647-654, 2006

Experience the Value of ASCO’s Global Community ASCO is unique in that we are the only organization that encompasses all oncology subspecialties, allowing our members to grow from the professional and personal expertise of their colleagues worldwide and across disciplines. Along with this multidisciplinary approach, ASCO membership offers you deep discounts on meeting registrations and premier publications like Journal of Clinical Oncology (JCO), as well as a host of other benefits, including: ● Advance access to Members’ Only Registration and Hotel Reservations for ASCO’s Annual Meeting ● Savings of 20% on ASCO University resources, including ASCO-SEP and the Oncology Literature Reviews ● Online advocacy tools and resources like ASCO in Action and the ASCO ACT Network For a full list of benefits specific to your membership category, visit benefits.asco.org. Not an ASCO member? Visit join.asco.org to fill out the online application and start receiving valuable member benefits.

54

JOURNAL

OF

ONCOLOGY PRACTICE



V O L . 11, I S S U E 1

Copyright © 2014 by American Society of Clinical Oncology

Downloaded from ascopubs.org by 37.44.207.184 on January 16, 2017 from 037.044.207.184 Copyright © 2017 American Society of Clinical Oncology. All rights reserved.

Febrile Neutropenia in Metastatic Cancer

Appendix Table A1. Demographic and Clinical Characteristics of Patients With Metastatic Solid Tumors Breast Cancer (n ⴝ 15,309)

Lung Cancer (n ⴝ 21,994)

Colorectal Cancer (n ⴝ 16,934)

Mean

58.0

62.4

59.8

60.3

SD

11.5

10.1

11.8

11.4

10.2

0.0

54.7

55.6

0.0

100.0

Northeast

16.4

17.8

16.7

17.5

16.3

Midwest

28.3

31.3

29.2

28.5

30.5

South

37.0

36.9

37.9

33.2

34.0

West

17.9

13.5

15.4

20.3

18.9

0.5

0.6

0.6

0.5

0.4

Characteristic*

Ovarian Cancer (n ⴝ 7,435)

Prostate Cancer (n ⴝ 4,668)

Age, years

Male sex, %

69.6

Geographic region of residence, %

Unknown Chronic comorbidities, % Cardiovascular disease

8.5

21.9

12.5

9.0

18.9

12.7

16.3

17.1

12.2

20.1

Liver disease

0.8

1.0

1.8

1.2

0.7

Lung disease

3.8

29.0

5.6

3.8

7.0

Renal disease

2.3

3.1

3.9

3.4

6.8

Diabetes

History of other conditions or events before chemotherapy course, % Anemia

21.4

25.2

34.6

31.0

29.6

Neutropenia

6.7

9.9

7.4

11.1

5.4

Other blood disorders

5.3

6.8

6.2

7.1

5.5

29.3

45.2

35.0

40.2

30.9

Infection History of hospitalization for any reason

37.0

58.5

66.8

78.9

34.6

History of infection-related hospitalization

10.6

22.1

19.4

20.0

11.3

History of FN-related hospitalization

0.7

1.0

0.4

1.0

0.6

History of chemotherapy

11.8

11.1

13.7

14.2

12.4

History of RT

24.8

47.7

12.3

3.8

26.8

Prechemotherapy expenditures, $ Mean

31,488

36,483

41,678

39,559

SD

33,975

37,747

44,678

43,010

23,926 33,621

Median

22,067

25,951

31,038

29,712

14,411

Interquartile range

28,108

33,911

39,418

32,835

21,785

Site of metastasis, % Bone

46.2

30.1

3.4

1.6

71.4

Liver

14.3

14.1

54.3

7.8

6.0

Brain

5.3

24.9

1.1

1.0

1.7

Lung

11.9

0.0

13.1

4.1

5.6

Peritoneum

1.3

0.5

10.3

37.4

1.0

Pleura

3.3

9.3

0.3

3.3

0.8

Large intestine

0.7

0.4

0.0

18.8

1.3

6.6

13.0

9.4

12.1

9.4

10.3

7.8

8.2

13.7

3.0

Other (site specified) Other (site unspecified)

continued on next page

Copyright © 2014 by American Society of Clinical Oncology

J A N U A R Y 2015



jop.ascopubs.org

Downloaded from ascopubs.org by 37.44.207.184 on January 16, 2017 from 037.044.207.184 Copyright © 2017 American Society of Clinical Oncology. All rights reserved.

Weycker et al

Table A1. (continued) Breast Cancer (n ⴝ 15,309)

Lung Cancer (n ⴝ 21,994)

Colorectal Cancer (n ⴝ 16,934)

Ovarian Cancer (n ⴝ 7,435)

Prostate Cancer (n ⴝ 4,668)

1

59.5

24.3

33.6

26.9

82.7

2

32.6

74.7

65.8

71.6

16.6

3

7.7

1.0

0.6

1.4

0.6

ⱖ4

0.2

0.1

0.0

0.0

0.1

2007

24.9

22.7

24.9

24.4

23.9

2008

23.6

23.1

23.0

23.9

23.0

2009

24.0

24.2

23.3

23.4

23.4

2010

19.8

20.9

20.4

20.0

20.7

2011

7.7

9.1

8.4

8.4

9.0

Characteristic* No. of myelosuppressive chemotherapy drugs, %

Year of chemotherapy, %

Abbreviations: FN, febrile neutropenia; RT, radiotherapy; SD, standard deviation. * Chronic comorbidities and history of blood disorders, infections, hospitalization, chemotherapy, and RT, as well as total health care expenditures, were assessed from beginning of 6-month pretreatment period to first day of chemotherapy.

JOURNAL

OF

ONCOLOGY PRACTICE



V O L . 11, I S S U E 1

Copyright © 2014 by American Society of Clinical Oncology

Downloaded from ascopubs.org by 37.44.207.184 on January 16, 2017 from 037.044.207.184 Copyright © 2017 American Society of Clinical Oncology. All rights reserved.

Suggest Documents