help button home button The Oncologist
HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
The Oncologist, Vol. 11, No. 10, 1095-1099, November 2006; doi:10.1634/theoncologist.11-10-1095
© 2006 AlphaMed Press

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow eLetters: Submit a response to this article
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article link to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Reprints/Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Murillo, J. R.
Right arrow Articles by Koeller, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Murillo, J. R., Jr.
Right arrow Articles by Koeller, J.

Lung Cancer

Chemotherapy Given Near the End of Life by Community Oncologists for Advanced Non-Small Cell Lung Cancer

Jose R. Murillo, Jr.a, Jim Koellerb,c

a Methodist Hospital, Houston, Texas, USA; b University of Texas at Austin, Austin, Texas, USA; c University of Texas Health Science Center, San Antonio, San Antonio, Texas, USA

Correspondence: Jim Koeller, M.S., University of Texas Health Science Center, Medicine—MSC-6220, 7703 Floyd Curl Drive, San Antonio, Texas 78229-3900, USA. Telephone: 210-567-8355; Fax: 210-567-8328; e-mail: koeller{at}uthscsa.edu

Received March 28, 2006; accepted for publication September 1, 2006.


   ABSTRACT
Top
 Abstract
Introduction
 Methodology
 Results
 Discussion
 Disclosure of Potential...
 References
 
Purpose. To characterize the chemotherapy given near the end of life to advanced non-small cell lung cancer (NSCLC) patients treated in the community oncology setting using a medical records database.

Methods. We conducted a retrospective chart review of expired advanced (stage IIIb/IV) NSCLC patients treated with chemotherapy. Patients who initiated chemotherapy in 2000–2003 were eligible. Patient demographics, all chemotherapy including dose and schedule, and disease-related events were collected.

Results. We report data from 10 community practices including 417 patients treated for advanced NSCLC in 2000–2003. The mean age was 67 years (median, 62 years) and 54% were male. Forty percent of patients were >69 years of age and 35% had an Eastern Cooperative Oncology Group performance status score of ≥2. First-line chemotherapy included combination therapy in 84% of patients. Second-line therapy was given to 56% of patients. Twenty-six percent of patients received third-line therapy, while 10% received fourth-line therapy and 5% received fifth-line therapy or greater. Patients received a mean of 6.1 cycles of chemotherapy. For patients receiving chemotherapy at the time of death, the mean line of therapy being given was second line. Chemotherapy was given within 1 month and 2 weeks of death to 43% and 20% of patients, respectively.

Conclusion. The availability of new chemotherapeutic agents has caused a subsequent increase in the length of time patients are receiving chemotherapy with advanced NSCLC. This would suggest an increased use of chemotherapy near the end of life, which was identified in this study.


   INTRODUCTION
Top
 Abstract
 Introduction
Methodology
 Results
 Discussion
 Disclosure of Potential...
 References
 
Over the past 15 years, several new treatment options have become available for the management of advanced (stage IIIb/IV) non-small cell lung cancer (NSCLC). These additional active agents (e.g., carboplatin, paclitaxel, gemcitabine, docetaxel, vinorelbine, gefitinib, erlotinib, pemetrexed) have now made first-, second-, and even third-line treatment of advanced NSCLC more commonplace. Both the American Society of Clinical Oncology’s updated 2003 NSCLC treatment guideline and the National Comprehensive Cancer Network (NCCN) NSCLC clinical practice guideline version 2.2006 acknowledge first-, second-, and third-line treatments of advanced NSCLC [1, 2]. However, even with these treatment advances, survival has incrementally increased by only 1.5–2.0 months [3–14]. This has the potential for blurring the lines between receiving what could appear to be acceptable chemotherapy and aggressively getting treatment too close to the time of death.

There have been few publications, most in abstract form, that have quantitatively described end-of-life chemotherapy strategies for cancer patients. In 2001, Emanuel et al. [15] reported the results of a review of over 7,900 Medicare cancer patients, in which 26% of patients received chemotherapy in the last 3 months of life, and 14% received chemotherapy within the last 1 month of life. With respect to lung cancer patients, 36%, 21%, and 11% received chemotherapy within 12, 3, and 1 months of death, respectively [15]. In 2003, Aragon-Ching et al. [16] reported the results from a single-institution study, in which 144 patients (27% lung cancer) received chemotherapy at the end of life. Of these, 26% received chemotherapy within 1 month of death and 43% received chemotherapy within 6 months of death. In 2002, Giorgi et al. [17] reported a review of clinical data for 193 patients (30%NSCLC) receiving end-of-life chemotherapy, of which 66% received treatment within 3 months of death and 33% received chemotherapy within 1 month of death. Again, no specifics related to the chemotherapeutic agents given or the line of therapy were provided. Finally, in 2004 Earle et al. [18] described results of a Medicare/Surveillance, Epidemiology, and End Results (SEER) database review of 8,155 chemotherapy-treated cancer patients in 1993–1996 (53% lung cancer) who were over the age of 64. The authors concluded that end-of-life chemotherapy usage patterns have become more aggressive, with almost 16% of patients receiving chemotherapy within 14 days of death. Again, there were no details provided describing the specific chemotherapy and line of therapy given.

Historically, many have categorized chemotherapy near the end of life as aggressive and typically unnecessary. However, most practitioners will counter that it can be difficult, if not impossible, to determine when the life of a patient with advanced disease will actually end. Current reports of this practice pattern clearly provide valuable information; however, they are not without limitation. As most of the data have come in abstract form, they lack specific information regarding both the types and lines of chemotherapy used, and most of the reports involved patients with various cancer types. Furthermore, the majority of the information available is a decade old and lacks patient and treatment specifics, with the exception of the Giorgi et al. [17] report. That report provides a more comprehensive approach, including details on chemotherapy regimen and line of treatment in a contemporary cohort of advanced NSCLC patients in a community oncology setting.


   METHODOLOGY
Top
 Abstract
 Introduction
 Methodology
Results
 Discussion
 Disclosure of Potential...
 References
 
This retrospective chart review, institutional review board–approved study evaluated advanced (stage IIIb/IV) NSCLC patients treated with chemotherapy in multiple community oncology practices in 2000–2003. This is an observational study only. In real-world terms, this database captured how the community oncologist approaches the treatment of NSCLC on a day-to-day basis. This study did not evaluate the physician–patient relationship and the specifics related to decisions made prior to each line of therapy. Data capture was carried out by a single, four-member research team. A cross-section of community practices from across the country was sought. Clinics needed to have at least three practicing medical oncologists and be willing and able to identify and locate the charts of lung cancer patients. Inclusion criteria included patients with a diagnosis of advanced NSCLC (stage IIIb, clinically any T, N3, M0 or T4, any N, M0; stage IV, clinically metastatic disease) who received chemotherapy as part of their primary treatment, and expired. Data were captured on a standardized form and included: (a) patient characteristics (age, gender, height, weight, performance status [PS] score at the start of chemotherapy, stage of disease, prior chemotherapy treatment, prior surgery, and prior radiation therapy); (b) treatment (all chemotherapy agents, dose, and schedule); and (c) disease-related events (progression of disease, stable disease, therapy completed, therapy changed, and the date of death). Because of the nature of a retrospective chart review and the inability to ensure accuracy and consistency across all patients, cause of death was not captured. All data from the sheets were then entered into a computerized database with a double check against the original form for entry accuracy.


   RESULTS
Top
 Abstract
 Introduction
 Methodology
 Results
Discussion
 Disclosure of Potential...
 References
 
From March to November 2003, 10 community oncology clinics from across the U.S. (e.g., Nevada, Louisiana, Indiana, Illinois, Kentucky, Maine, Connecticut, and Florida) were visited for data capture. Four hundred seventeen expired patients comprised the database. Data were captured from the time of first chemotherapy treatment (with or without radiation therapy) to the time of death. Twenty-two percent of patients received chemotherapy in 2003, 36% received chemotherapy in 2002, 27% received chemotherapy in 2001, and 15% received chemotherapy in 2000. Patient demographics can be found in Table 1Go. Fifty-four percent of patients were men. The mean age was 67 years; however, 40% of patients were >69 years of age. The majority of patients (73%) had stage IV disease, and 65% of patients had an Eastern Cooperative Oncology Group PS score at the initiation of treatment of 0–1. Of the 35% of patients who had a PS score ≥ 2, only 14 (3%) had a PS score of 3 at the start of therapy. Ten percent of patients received prior surgery, 10% received prior chemotherapy, and 20% received prior radiation therapy.


View this table:
[in this window]
[in a new window]
  		Table 1. Patient demographics (n = 417)

 
Overall, 417 patients received a total of 2,551 cycles of chemotherapy (Table 2Go), with a majority of those cycles given as first-line treatment (57%). Fifty-six percent of patients received second-line therapy, while 26%, 10%, and 7% received third-, fourth-, and fifth-line therapy, respectively. The mean number of total chemotherapy cycles per patient was 6.1 (3.5 cycles first line, 2.6 cycles second line, 2.8 cycles third line, 2.7 cycles fourth line, and 2.4 cycles fifth line). The 6.1 cycles of overall chemotherapy required a total of 6.1 months to administer. Eighty-three percent of patients received a chemotherapy combination as first-line treatment. Combination chemotherapy was also used as second-line (42%) and third-line (23%) treatment. A variety of agents and regimens was identified (Table 3Go). Great variability in treatment was seen at all clinics and across all lines of therapy. No consistent patterns of treatment were identified among the clinics.


View this table:
[in this window]
[in a new window]
  		Table 2. Chemotherapy treatment

 

View this table:
[in this window]
[in a new window]
  		Table 3. Chemotherapy regimens

 
For poorer PS patients (PS score ≥ 2), carboplatin plus paclitaxel was still the primary regimen used, although 26% of patients received single-agent first-line treatment, compared with 18% for the total population. Also, only 38% and 13%, respectively, received second- and third-line therapy compared with 56% and 26%, respectively, for the total population. Treatments for patients >70 years of age were similar to those of poorer performance patients, with carboplatin plus paclitaxel being the primary regimen and 26% of patients receiving single agents as first-line therapy. Also, 46% and 17% of patients were able to receive second- and third-line therapy, respectively.

The primary difference in treatment identified between stage IIIb and IV patients was the use of concurrent radiation therapy (XRT). Fifty-eight percent of stage IIIb patients received concurrent XRT with the first cycle of chemotherapy, compared with only 14% for stage IV patients. However, the progression of treatment from first- to second- to third-line and greater therapy was similar between the two stages.

One hundred eighty-one patients (43%) received chemotherapy within 1 month (≤31 days) of death. Of those, 39% received first-line, 28% received second-line, and 21% received third-line treatment. For patients who received chemotherapy within 2 weeks (≤14 days) of death (20%), 39% received first-line, 28% received second-line, and 18% received third-line treatment (Table 4Go). Looking specifically at gefitinib (for which use was mainly protocol based and with U.S. Food and Drug Administration approval coming near the end of the data capture period), 19% of patients received treatment within 1 month of death and 10% of patients received treatment within 14 days of death. Patients on average had received 2.1 lines of therapy at the time of death. The mean and median times from last chemotherapy treatment to death were 2.6 and 1.6 months, respectively.


View this table:
[in this window]
[in a new window]
  		Table 4. Time to death from last chemotherapy treatment

 

   DISCUSSION
Top
 Abstract
 Introduction
 Methodology
 Results
 Discussion
Disclosure of Potential...
 References
 
The availability of new active agents has lengthened the chemotherapy treatment timeline of advanced NSCLC, and thus may also have increased the likelihood of receiving treatment closer to the time of death. From these data, 43% of patients received chemotherapy within 1 month of death, compared with 11% [14], 26% [15], and 33% [15] reported from other trials. Chemotherapy within 2 weeks of death was seen in 20% of patients in this study, compared with 16% reported in a previous study [16]. The overall rates of treatment within 1 month and 2 weeks of death in this study are higher than those published previously.

This evaluation is more comprehensive in that it identified the chemotherapy regimen and the lines of therapy given from the initiation of treatment to death. For patients who received chemotherapy within 1 month of death, 88% received first-line (39%), second-line (28%), or third-line (21%) therapy. For patients who received chemotherapy within 2 weeks of death, 85% received first-line (39%), second-line (28%), or third-line (18%) therapy. At the time of death, the majority of patients were receiving second-line therapy. Unfortunately, we captured only the start-of-treatment PS score, and did not capture PS with subsequent lines of therapy because of the inconsistency of information available through this retrospective data capture. Also as a result of consistency problems, we were unable to capture cause of death. In addition, we were unable to get a handle on physician–patient interactions tied to the decisions made related to the progression of treatment.

These data demonstrate an increased use of chemotherapy near or at the time of death. As described by Earle et al. [18], aggressive treatment may be part of the reason. However, some of this behavior may actually be related to the availability of more treatment choices for advanced NSCLC. The potential of using targeted therapies as longer-term maintenance treatment has been reviewed and this could be one justification for patients receiving therapy nearer to the time of death [19]. However, in our database, the percentage of patients receiving gefitinib near the end of life was not higher than those receiving other chemotherapy. Another potential factor may be the physician’s inability to predict the life expectancy of advanced NSCLC patients. Also, with the availability of medical information on the Internet and direct-to-consumer advertising, patients come to physicians asking for and sometimes, almost demanding specific or additional treatment.

This report is missing information related to the decision process associated with the progression of therapy from first- to second- to third-line and greater treatment. Also, it is missing the PS score at last line of therapy and cause of death. Prospective evaluations including patient factors, PS, detailed disease-related information, and the chemotherapy treatment given near or at the time of death in the advanced NSCLC patient population can help define its appropriateness. However, we hope this report fosters additional dialogue and follow-up studies related to the appropriateness of therapy at or near the end of life for advanced NSCLC patients.


   DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST
Top
 Abstract
 Introduction
 Methodology
 Results
 Discussion
 Disclosure of Potential...
References
 
J.K. has acted as a consultant for BMS sanofi-aventis.


   ACKNOWLEDGMENT
Top
 Abstract
 Introduction
 Methodology
 Results
 Discussion
 Disclosure of Potential...
 References
 
This study was funded by a research grant provided by Eli Lilly & Company.


   REFERENCES
Top
 Abstract
 Introduction
 Methodology
 Results
 Discussion
 Disclosure of Potential...
 References
 

  1. Pfister DG, Johnson DH, Azzoli CG et al. American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: update 2003 J Clin Oncol 2004;22:330–353.
  2. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology, version v.2.2006. Non-small cell lung cancer. NCCN, 2006:1–50.
  3. Breathnach OS, Freidlin B, Conley B et al. Twenty-two years of phase III trials for patients with advanced non-small cell lung cancer: sobering results. J Clin Oncol 2001;19:1734–1742.[Abstract/Free Full Text]
  4. Schiller JH, Harrington D, Belani CP et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002;346:92–98.[Abstract/Free Full Text]
  5. Shepherd FA, Dancey J, Ramlau R et al. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol 2000;18:2095–2103.[Abstract/Free Full Text]
  6. Fossella FV, DeVore R, Kerr RN et al. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. J Clin Oncol 2000;18:2354–2362.[Abstract/Free Full Text]
  7. Manegold C. Chemotherapy for advanced non-small cell lung cancer: standards. Lung Cancer 2001;34(suppl 2):S165–S170.[Medline]
  8. Fossella FV. Pemetrexed for treatment of advanced non-small cell lung cancer. Semin Oncol 2004;31(suppl 1):100–105.[CrossRef][Medline]
  9. Hanna N, Shepherd FA, Fossella FV et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol 2004:22:1589–1597.[Abstract/Free Full Text]
  10. Kelly K, Averbuch S. Gefitinib: phase II and III results in advanced non-small cell lung cancer. Semin Oncol 2004;31(suppl 1):93–99.[CrossRef][Medline]
  11. Fuster LM, Sandler AB. Select clinical trials of erlotinib (OSI-774) in non-small-cell lung cancer with emphasis on phase III outcomes. Clin Lung Cancer 2004;6(suppl 1):S24–S29.[Medline]
  12. Gridelli C. The ELVIS trial: a Phase III study of single-agent vinorelbine as first-line treatment in elderly patients with advanced non-small cell lung cancer. The Oncologist 2001;6(suppl 1):4–7.[Abstract/Free Full Text]
  13. Gridelli C. Does chemotherapy have a role as palliative therapy for unfit or elderly patients with non-small-cell lung cancer? Lung Cancer 2002;38(suppl 2):S45–S50.[Medline]
  14. Gridelli C, Perrone F, Gallo C et al. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst 2003;95:362–372.[Abstract/Free Full Text]
  15. Emanuel EJ, Young-Xu Y, Ash A et al. How much chemotherapy are cancer patients receiving at the end of life? Proc Am Soc Clin Oncol 20;2001:239.
  16. Aragon-Ching JE, Cohen JB, Cohen A et al. Chemotherapy at the end of life. Proc Am Soc Clin Oncol 22;2003:776.
  17. Giorgi F, Bascioni R, Brungni M. Chemotherapy use at the end of life: decision making process. Pro Am Soc Clin Oncol 2004;23:537.
  18. Earle CC, Neville BA, Landrum MB et al. Trends in the aggressiveness of cancer care near the end of life. J Clin Oncol 2004;22:315–321.[Abstract/Free Full Text]
  19. Massarelli E, Herbst RS. Use of novel second-line targeted therapies in non-small cell lung cancer. Semin Oncol 2006;33(suppl 1):S9–S16.[Medline]



This article has been cited by other articles:


Home page
 Ann OncolHome page
S. Kao, J. Shafiq, J. Vardy, and D. Adams
Use of chemotherapy at end of life in oncology patients
Ann. Onc., September 1, 2009; 20(9): 1555 - 1559.
[Abstract] [Full Text] [PDF]

Home page
 Jpn J Clin OncolHome page
J.-M. Sun, K.-W. Lee, J. H. Kim, Y. J. Kim, H. I. Yoon, J.-H. Lee, C.-T. Lee, and J. S. Lee
Efficacy and Toxicity of Pemetrexed as a Third-line Treatment for Non-small Cell Lung Cancer
Jpn. J. Clin. Oncol., January 1, 2009; 39(1): 27 - 32.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
J. W. Mack, S. Joffe, J. M. Hilden, J. Watterson, C. Moore, J. C. Weeks, and J. Wolfe
Parents' Views of Cancer-Directed Therapy for Children With No Realistic Chance for Cure
J. Clin. Oncol., October 10, 2008; 26(29): 4759 - 4764.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
C. C. Earle, M. B. Landrum, J. M. Souza, B. A. Neville, J. C. Weeks, and J. Z. Ayanian
Aggressiveness of Cancer Care Near the End of Life: Is It a Quality-of-Care Issue?
J. Clin. Oncol., August 10, 2008; 26(23): 3860 - 3866.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
S. E. Harrington and T. J. Smith
The Role of Chemotherapy at the End of Life: "When Is Enough, Enough?"
JAMA, June 11, 2008; 299(22): 2667 - 2678.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
G. P. Kalemkerian
Guidelines Are Never Enough: A Commentary on "When Guidelines Are Not Enough"
J. Clin. Oncol., May 1, 2007; 25(13): 1810 - 1811.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow eLetters: Submit a response to this article
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article link to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Reprints/Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Murillo, J. R.
Right arrow Articles by Koeller, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Murillo, J. R., Jr.
Right arrow Articles by Koeller, J.

HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
THE ONCOLOGIST STEM CELLS CME ALPHAMED PRESS JOURNALS