Annals of Oncology Advance Access originally published online on November 15, 2005
Annals of Oncology 2006 17(2):211-216; doi:10.1093/annonc/mdj043
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2005 European Society for Medical Oncology
Dealing with metastatic breast cancer in elderly women: results from a French study on a large cohort carried out by the ‘Observatory on Elderly Patients’
1 Centre Hospitalier Lyon Sud, service d'oncologie, Pierre Bénite; 2 Institut Paoli Calmettes, Marseille; 3 Hôpital Charles Foix, Ivry sur Seine; 4 Institut Gustave Roussy, Villejuif; 5 Clinique Saint-Jean, Lyon; 6 Chugai Pharma France, Paris La Défense Cedex; 7 A+A Healthcare Marketing Research, Lyon; 8 Hôpital Henri Mondor, Créteil, France
* Correspondence to: Dr G. Freyer, Centre Hospitalier Lyon Sud, Service Oncologie, 165 Chemin du Grand Revoyet, 69495 Pierre Bénite, France. Tel: +33-4-78-86-43-16; Fax: +33-4-78-86-43-19; E-mail: gilles.freyer{at}chu-lyon.fr
 |
Abstract |
|---|
 Top Abstract introductionpatients and methodsresultsdiscussionReferences |
|---|
Background: Treatment of elderly patients with metastatic breast cancer (MBC) is not clearly defined and seems to vary according to the subjective appreciation of the physician.
Patients and methods: After interviewing 107 French specialists qualified in oncology, data concerning 1009 MBC patients were collected: 500 patients were between 65 and 74 years and 509 were >75 years of age. Differences in diagnosis and treatment strategy were analyzed for both age groups to identify the physician's criteria of choice and the eventual use of the geriatric assessment among those criteria.
Results: At diagnosis, synchronous metastatic disease was more frequent in patients over 75 years old (52% versus 39%; P <0.001). Physicians indicated that treatment was based on age and on a subjective evaluation of the patient's general status. Sixty-eight per cent of younger patients and only 31% of older ones received chemotherapy (P <0.001). In the older group drug doses were lower than those usually recommended in three-quarters of cases. Only 10% of physicians considered that they under-treat patients using the FEC 50 regimen. Over 75 years of age, hormone therapy was offered to most patients, including 8% with hormone-independent tumors. Geriatric covariates were never considered. Geriatricians rarely, if ever, played a role in the therapeutic decision.
Conclusions: Inclusion of elderly patients with MBC in prospective trials is warranted to define standards of care and reduce heterogeneity in the decision-making process.
Key words: breast, decisional criteria, elderly, metastatic, survey
|
introduction |
|---|
|
TopAbstractintroductionpatients and methodsresultsdiscussionReferences |
|---|
Breast cancer remains a major public health problem in Western Europe and the USA. It is the most frequently diagnosed tumor in women and its incidence increases with age [1
]. Over the next few decades, a constant increase of life expectancy will mean that most breast cancers will occur in elderly women and that in many of them distant metastases will occur, requiring systemic treatments. However, the principles of treatment are not as well established in older as in younger women. While the process for diagnosing and treating metastatic breast cancer (MBC) in younger women is relatively well defined, based on determining prognostic factors such as time lapse before recurrence, hormone receptors status, number of metastatic sites and Her2-neu overexpression, treatment of older women seems to be based above all on the physician's experience. Under-treatment owing to the risk of side-effects is usually reported [2, 3]. This empirical attitude might have deleterious consequences for some patients, since a number of studies have shown the good tolerance and efficacy of chemotherapy in various tumor types [4–6]. However, the major characteristic of the population of elderly patients is heterogeneity: some will tolerate chemotherapy as well as younger patients, while some others will experience unpredictable and severe side-effects [7, 8]. A possible way to overcome this variability and therefore to discriminate the patients ‘at risk’ is to use parameters based on the Comprehensive Geriatric Assessment, a global approach for the elderly patient [9–18]. Such parameters remain to be fully evaluated in the oncological setting through prospective trials. Several studies have examined the reasons for the under-representation of elderly patients in clinical trials [19–21], yet few studies have been focused on the oncologist's diagnosis and therapeutic approach faced with MBC in the elderly woman. This study reports the results of an investigation undertaken in France in the context of the ‘Observatory on Elderly Patients’. The aims of the study were to determine whether older patients received various treatments with or without explicit motivation and whether the elements of geriatric assessment were used in the decision-making process.
|
patients and methods |
|---|
|
TopAbstractintroductionpatients and methodsresultsdiscussionReferences |
|---|
survey
A prospective survey was carried out in France from 22 October to 18 December 2002. The questionnaire (see Appendix 1, supplementary data), produced by a board of experts in the fields of oncology and gerontology, was applied by a private survey agency (A+A Healthcare Research, Lyon, France) to physicians randomly chosen from a non-exhaustive list of specialists in medical oncology or other specialists qualified in oncology including the different kind of health centers in France. The physicians were selected from professional directories and randomly called by the A+A Healthcare Research agency. If they satisfied the selection criteria and accepted to participate in the survey, they were chosen. There was a homogenous geographic distribution in France to avoid choosing all physicians in the same place and the health centers and departments where a physician was already recruited were gradually eliminated. Centers whose physicians collaborated in the creation of the questionnaire were not allowed to participate in the survey. Using this methodology, our purpose was to reflect the reality as well as the variety of the clinical situations usually observed in France.
The questionnaire was designed to collect data on how the diagnosis and the treatment of MBC were carried out, as well as the physician's profile, the factors influencing decisions regarding the treatment, the characterization of the patients' disease and their psychosocial profile.
Physicians were asked to take into consideration their last 10 patients admitted for MBC over 65 years of age: five patients between 65 and 74 years old and five patients >75 years old.
physicians and health centers
A total of 107 French specialists were interviewed: 69 medical oncologists, 27 radiotherapists, five gynecologists, five physicians certified in internal medicine and one pneumologist qualified in oncology. The physicians were randomly recruited. Only the physicians fulfilling the condition of managing 10 MBC patients, at least five of whom were between 65 and 74 years and five >75 years old, were eligible for the survey analysis. Their distribution according to the kind of health institution is reported in Figure 1.
|
Forty-nine per cent of physicians had more than 10 years of oncology practice, 75% of them had more than 50 patients with breast cancer in their active file and 44% of them had more than 50 MBC patients in their active file.
statistics
Proportional tests (mainly Student's t-tests) were used to compare different variables (e.g. age, disease stage, decisional reasons) and frequency among the subpopulations analyzed.
Significant differences are expressed with P <0.5, P <0.1, P <0.01, P <0.001 and P <0.0001.
Correlation was estimated to determine, among the criteria submitted to physicians, those that were more correlated to the choice of a treatment identical to that indicated for a 55-year-old patient, as well as the choice of a given chemotherapy regimen.
Discriminant function analysis and segmentation were used to identify the criteria needed to construct a chemotherapy prescription model and to organize them in a hierarchy system.
Discriminating analysis [22] covers two aspects: the first consists in determining the discriminating characteristics of a population divided into groups, whereas the second is decisional and helps to assign a new individual to a group. Alternative techniques, such as the construction of decision trees (methods of segmentation), also meet decisional aims. The software used was SPSS.
|
results |
|---|
|
TopAbstractintroductionpatients and methodsresultsdiscussionReferences |
|---|
patients
Data were collected from 1009 patients with MBC: 500 patients from 65 to 74 years of age (average 68.6 ± 0.3; 95% CI) and 509 patients >75 years of age (average 79.6 ± 0.4; 95% CI).
The degree of dependence was evaluated by the physician without a specific scale or questionnaire: 77% of patients between 65 and 74 years old were considered independent for the instrumental activities of daily living versus 50% of patients >75 years old (P <0.0001). Twenty-five per cent of the younger patients were considered as having an Eastern Cooperative Oncology Group (ECOG) performance status 0 versus 9% of patients >75 years of age (P <0.0001). Eighty-four per cent of the younger patients lived at home in comparison with 56% of older patients (P <0.0001).
disease
As shown in Figure 2, the disease stage at diagnosis differed significantly between groups. Fifty-two per cent of patients >75 years of age had metastatic disease at diagnosis compared with 39% of patients between 65 and 74 years old (P <0.0001).
|
For both age groups, metastasis occurred more commonly in bone, followed by visceral metastases (liver and lung). Sixty-five per cent of patients over the age of 75 years had bone metastasis in comparison with 57% of younger patients (P <0.01). Metastases in visceral sites (liver, lungs, lymph nodes and brain) had equivalent relative frequencies (Figure 3).
|
There was no significant difference in the frequency of positive hormone receptors between age groups. Among the patients tested, estrogen and progesterone receptors were found to be present in 83% and 75%, respectively, of patients >75 years of age compared with 79% and 70% of patients between 65 and 74 years old (not significant).
Her2 overexpression was tested less frequently in older patients than in their younger counterparts. The test was not carried out in 80% of patients >75 years of age, in comparison with 65% of patients between 65 and 74 years old (P <0.0001).
treatment
There was no significant difference among the various health institutions concerning the access of patients to therapy (no center effect). The percentages of patients treated and the kind of treatment delivered in public and private centers were equivalent.
The same laboratory tests (blood counts, hepatic and renal function evaluation) and cardiac screening (ECG and echographic evaluation of left ventricular ejection fraction) were performed for both age groups before chemotherapy. No other particular exam was done for older patients.
Among patients >75 years of age presenting with metastasis of breast cancer at diagnosis, 69% did not receive any chemotherapy compared with 32% of patients between 65 and 74 years old (P <0.005).
Hormone therapy was the treatment of choice for patients over 75 years old (Figure 4), whereas chemotherapy was more frequently prescribed for patients between 65 and 74 years old.
|
Radiotherapy and supportive care had homogeneous indications for both groups.
Trastuzumab use was more frequent in younger patients: 9% versus 2% (P <0.001). In the younger group of patients, the treatment with trastuzumab/Her2 overexpression ratio was 64%, in comparison with 30% in the group of older women (not significant).
Among women receiving hormone therapy, 8.2% and 7.3% of older versus younger ones had negative hormone-receptor tumors, respectively (not significant). Among women receiving chemotherapy, 79% and 76.8% older versus younger ones had positive hormone-receptor tumors (not significant).
When chemotherapy was indicated for the treatment of metastatic disease, FEC (fluorouracil, epirubicin and cyclophosphamide) was the reference chemotherapy for both groups. It was prescribed in 27% of patients between 65 and 74 years old and in 22% of the older patients (not significant). Considering patients treated with chemotherapy, FEC <60 was the regimen of choice for women >75 years of age (69% versus 41% in the younger patients; P <0.01) whereas FEC 75–100 was preferred for 50% of patients between 65 and 74 years old versus 22% of those above >75 years (P <0.01), as shown in Figure 5.
|
Paclitaxel and docetaxel were prescribed in 15% and 17% of patients between 65 and 74 years old and in 11% and 14% of patients >75 years of age, respectively (not significant). Vinorelbine was given to 7% of younger patients and to 12% of older patients (not significant). Capecitabine or 5-fluorouracil was given to 8% of patients between 65 and 74 years and to 12% of older patients (not significant).
There was no difference between groups with regards to granulocyte colony-stimulating factor prophylaxis for chemotherapy-induced neutropenia, since 32% of patients >75 years of age received this drug in comparison with 24% of the younger patients (not significant).
impact of age on therapeutic decision
The treatment used was considered to be standard in dose and cycle duration for 62% of women >75 years old and for 82% between 65 and 74 years old (P <0.01). Standard treatment was considered to be the reference treatment in a given center.
When asked if patients would receive different treatment if they were 55 years old, physicians answered ‘yes’ for 62% of patients >75 years and for 35% of patients between 65 and 74 years old (P <0.0001).
Age was found to be a strongly discriminating factor: in the discriminant function analysis, 76.5 years old was the age above which patients were treated in a different way in comparison with younger ones.
However, when asked to explain why older patients were treated with weaker doses of chemotherapy, physicians pointed out that a subjective evaluation of the general health status was the most important criterion. Sixty-three per cent of patients >75 years of age were considered to have inadequate physical status versus 25% in the younger group (P <0.001). Other variables pointed out by physicians did not reach statistical significance between groups: age, heart failure, hepatic or renal insufficiency, or toxicity of previous chemotherapy.
participation of professionals in the therapeutic decision
In the group of patients between 65 and 74 years old, the treatment was chosen by only one physician in 30% of cases compared with in 43% of the older patients (P <0.01). This amounts to saying that a collective decision was taken in 70% of 65–74 year old cases compared with 57% of the older patients. Moreover, geriatricians were almost never involved in the treatment discussions (only 2% of older cases and 0% for their younger counterparts) (Figure 6).
|
Final decision-making about therapy options was the responsibility of medical oncologists in 52% and radiotherapists in 34% of cases for younger patients, and in 46% and 32%, respectively, in older patients.
|
discussion |
|---|
|
TopAbstractintroductionpatients and methodsresultsdiscussionReferences |
|---|
This study is the first report on the current practice of MBC management among elderly patients in France. It clearly confirms the existence of major differences, based solely on age, in dealing with MBC between elderly women and their younger counterparts. The population concerned by this study is a sample of the population of patients suffering from breast cancer, since it was carried out among oncologists and, as might give cause for concern based on the fact that diagnosis occurred that much later the older the patient, a significant proportion of elderly patients are not sent to an oncologist. To overcome this methodological limitation, more investigations should be performed into practices among specialists of internal medicine and geriatricians. Concerning the major role of chronological age on the overall quality of care in elderly patients with cancer, our results are concordant with those published previously [2
, 5]. Another important piece of information is the statistical cut-off of 76.5 years, which leads us to distinguish between two subgroups in which medical decision-making varies dramatically. From this highly pragmatic point of view, one could consider that an over 76.5-year-old cancer patient with MBC is an ‘elderly’ patient, in the absence of any other acceptable definition of a biological or physiological age. However, since this cut-off point was determined a posteriori, we will discuss the results of our study in the two groups as they were initially defined.
Over 75 years of age, diagnosis is made at a later stage of the disease, with more patients presenting with initial metastasis. This fact has already been reported in other tumor types such as ovarian carcinoma, which is most often diagnosed at the stage of diffuse peritoneal carcinomatosis [4]. This could be due to the tendency of both elderly patients and physicians to neglect the clinical signs of the disease.
It is noteworthy that the number and distribution of metastatic sites are not influenced by age in our study. However, we must emphasize that this result may be biased by a possible under-diagnosis in elderly women. In particular, we cannot ensure that visceral metastasis was investigated in all cases when the existence of bone involvement was known a priori.
As expected, taking into account the current observed tendencies about cancer care in the elderly, treatment is the most heterogeneous and variable step of the overall health-care system [23]. One preliminary explanation amongst many others could be reduced access to transport, the deleterious consequences of which on optimal treatment have already been emphasized [24].
In this study, most patients received hormone therapy, which is the reference first-line treatment in this population. However, 8% of patients received hormone-therapy despite having hormone-resistant tumors. In those patients, this treatment can be considered as non-optimal. Moreover, checking on Her2-neu overexpression is anecdotal, thus reducing the possibility of using a targeted therapy such as trastuzumab alone or in combination with chemotherapy, the most powerful therapeutic alternative in the corresponding subgroup of patients [25]. In this case, the fear of toxicity should not be evoked to explain a suboptimal procedure, since this agent is known to be well-tolerated.
Concerning the therapeutic choice, anthracyclin remain the reference treatment but doses are frequently reduced, providing demonstrably ineffective treatment [26]. These results are, moreover, contrary to those recorded in a previously published adjuvant trial showing that optimal doses of epirubicin can be delivered with acceptable tolerance in elderly patients [27]. However, a possible increase in the risk of cardiotoxicity was recently discussed in the report of a smaller study in elderly patients treated with oral idarubicin for MBC [8].
Under-treatment is not considered an anomaly by oncologists in our study compared with the standards usually permitted for younger patients. Nevertheless, this under-treatment maintains the first-intention position of anthracyclins, even at reduced doses, rather than other agents such as oral vinorelbine that might appear more attractive in optimizing the toxicity/benefit ratio in such a fragile population [28]. This observation of under-treatment is supported by a recent study concerning the limits regarding the participation of elderly patients in therapeutic trials: the fear of toxicity is the main criterion and the decider is the physician [19].
It should be noted that we observed no reduction in G-CSF prescriptions in older patients, in accordance to the opinion of a number of experts in the field of geriatric oncology, as expressed in the recently published European Organization for Research and Treatment of Cancer guidelines [29]. It seems that the clinicians' fear of hematological toxicity largely counterbalances their potential reticence due to an increased economical cost.
In our study, the criteria and procedure of choice are no different from those used for younger patients, but they clearly lead to questionable decisions. Chronological age itself does not cause any additional assessment to be undertaken. Evaluation of the state of health is based solely on the ECOG performance status, as part of a more subjective and questionable concept of ‘general health status’, and the multidisciplinary team dictating the therapeutic strategy almost never includes a geriatrician. However, Repetto et al. [9] have shown that more parameters than the performance status should be considered in elderly patients. There are countless references to the need for a multidimensional geriatric assessment before any treatment is given [9–18]. Such an evaluation would make it possible to discover specific health problems related to older age and, in particular, dependence and comorbidity. Our study shows that the elements of geriatric assessment are rarely used in the daily practice and that the therapeutic decision appears arbitrary. To overcome this limitation, the collaboration of a geriatrician or, alternatively, specific training of all physicians in the field of geronto-oncology could be proposed. Educating oncologists to carry out simple, brief screening so as to obtain an overall, albeit certainly imperfect, picture of the elderly patient will probably take as long as it will take to educate the general practitioner or the geriatrician to appreciate the feasibility of chemotherapy after the age of 70 years. Specific research programmes are currently underway in various areas to attempt to introduce all specialists to the fundamentals of this evaluation.
Another important issue is the prospective validation of some specific tools using the data coming from the multidimensional geriatric evaluation to predict the tolerance and efficacy of anticancer treatments. This can be done in prospective studies by prognostic analyses including geriatric covariates [30].
This prospective study highlights the differences in dealing with MBC based solely on age. As oncologists consider it to be discriminating, as well as the variable and approximative concept of ‘general status’, breast cancer is never treated to a more in-depth evaluation but to suboptimal procedures for most patients, with the risk of being ineffective. Most oncologists and geriatricians still have to learn how to cooperate with each other and implementation of the complementarity of their skills is yet to be realized.
|
Acknowledgements |
|---|
The authors wish to thank the members of the French Observatory on Elderly patients [oncologists: A. C. Braud, G. Freyer, J. P. Martin, M. Spielmann, L. Zelek; hematologists: T. Facon (Hôpital Claude Huriez, 1 place de Verdun, 59037 Lille, France), P. Rodon (Centre hospitalier, mail Pierre Charlot, 41016 Blois Cedex, France), B. Rio (Hôpital Hôtel Dieu, 1 parvis Notre Dame, 75004 Paris, France); geriatrician: P. Chaibi], A+A healthcare Marketing Research and Chugai Pharma France. In memoriam, we wish to express our gratitude to Doctor Anne-Chantal Braud in token of her enthusiasm and her involvement in this project.
Supplementary data to this article is available online at http://annonc.oxfordjournals.org
|
Notes |
|---|
Deceased. 
Received for publication July 4, 2005. Revision received September 14, 2005. Accepted for publication September 14, 2005.
|
References |
|---|
|
TopAbstractintroductionpatients and methodsresultsdiscussionReferences |
|---|
1. Ries LAG, Eisner MP, Kosary CL et al. SEER Cancer Statistics Review 1973–1999. National Cancer Institute 2002.
2. McKenna RJ. Clinical aspects of cancer in the elderly. Cancer 1994; 74: 2107–2117.[CrossRef][Web of Science][Medline]
3. Castiglione M, Gelber RD, Goldhirsch A. Adjuvant systemic therapy for breast cancer in the elderly: competing causes of mortality. J Clin Oncol 1990; 8: 519–526.[Abstract]
4. Gershenson DM, Follen Mitchell M, Atkinson N et al. Age contrasts in patients with advanced epithelial ovarian cancer: the MD Anderson Cancer Center experience. Cancer 1993; 71: 638–643.[Medline]
5. Ibrahim N, Frye D, Buzdar A et al. Doxorubicin-based chemotherapy in elderly patients with metastatic breast cancer: tolerance and outcome. Arch Intern Med 1996; 156: 882–888.
6. Kennedy BJ. Ageing and cancer. J Clin Oncol 1988; 6: 1903–1911.[Medline]
7. Balducci L, Extermann M. Management of cancer in the older person: a practical approach. Oncologist 2000; 5: 224–237.
8. Freyer G, Lortholary A, Delcambre C et al. Unexpected toxicities in elderly patients treated with oral idarubicin in metastatic breast cancer: the GINECO experience. Clin Oncol 2004; 16: 17–23.[CrossRef]
9. Repetto L, Fratino L, Audisio RA et al. Comprehensive geriatric assessment adds information to Eastern Cooperative Oncology Group performance status in elderly cancer patients: an Italian Group for Geriatric Oncology Study. J Clin Oncol 2002; 20: 494–502.
10. Monfardini S, Balducci L. A comprehensive geriatric assessment (CGA) is necessary for the study and the management of cancer in the elderly. Eur J Cancer 1999; 35: 1771–1772.[CrossRef][Web of Science][Medline]
11. Zagonel V. Importance of a comprehensive geriatric assessment in older cancer patients. Eur J Cancer 2001; 37 (Suppl 7): S229–S233.
12. Naeim A, Reuben D. Geriatric syndromes and assessment in older cancer patients. Oncology 2001; 15: 1567–1577.[Medline]
13. American Geriatric Society Public Policy Committee. Comprehensive geriatric assessment. J Am Geriatr Soc 1989; 37: 473–474.[Web of Science][Medline]
14. Solomon D, Brown AS, Brummel-Smith K et al. NIH Consensus Panel. National Institutes of Health Consensus Development Conference Statement: geriatric assessment methods for clinical decision-making. J Am Geriatr Soc 1998; 36: 342–347.
15. Rubenstein LZ, Josephson KR, Wieland GD et al. Effectiveness of a geriatric evaluation unit. A randomized clinical trial. N Engl J Med 1984; 311: 1664–1670.[Abstract]
16. Stuck AE, Siu AL, Wieland GD, Rubinstein LZ. Comprehensive geriatric assessment: a meta-analysis of controlled trials. Lancet 1993; 342: 1032–1036.[CrossRef][Web of Science][Medline]
17. Monfardini S, Ferruci L, Fratino L et al. Validation of a multidimensional evaluation scale for use in elderly cancer patients. Cancer 1996; 77: 395–401.[CrossRef][Web of Science][Medline]
18. Extermann M. Studies of Comprehensive Geriatric Assessment in patients with cancer. Cancer Control 2003; 10: 463–468.[Medline]
19. Kemeny MM, Peterson BL, Kornblith AB et al. Barriers to clinical trial participation by older women with breast cancer. J Clin Oncol 2003; 21: 2268–2275.
20. Hutchins LF, Unger JM, Crowley JJ et al. Under-representation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 1999; 341: 2061–2067.
21. Kornblith AB, Kemeny M, Peterson BL et al. Survey of oncologists' perceptions of barriers to accrual of older patients with breast carcinoma to clinical trials. Cancer 2002; 95: 989–996.[CrossRef][Web of Science][Medline]
22. Press SJ, Wilson S. Choosing between logistic regression and discriminant analysis. J Am Stat Assoc 1978; 73: 699–705.[CrossRef][Web of Science]
23. Balducci L, Yates J. General guidelines for the management of older patients with cancer. Oncology 2000; 14: 221–227.[Medline]
24. Goodwin JS, Hunt WC, Samet JM. Determinants of cancer therapy in elderly patients. Cancer 1993; 72: 594–601.[CrossRef][Web of Science][Medline]
25. Slamon DJ, Leyland-Jones B, Shak S et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001; 15: 783–792.
26. French Epirubicin Study Group. Epirubicin-based chemotherapy in metastatic breast cancer patients: role of dose-intensity and duration of treatment. J Clin Oncol 2000; 18: 3115–3124.
27. Wils JA, Bliss JM, Marty M et al. Epirubicin plus tamoxifen versus tamoxifen alone in node-positive postmenopausal patients with breast cancer: A randomized trial of the International Collaborative Cancer Group. J Clin Oncol 1999; 17: 1988–1998.
28. Freyer G, Delozier T, Lichinister M et al. Phase II study of oral vinorelbine in first-line advanced breast cancer chemotherapy. J Clin Oncol 2003; 21: 35–40.
29. Repetto L, Biganzoli L, Koehne CH et al. EORTC Cancer in the Elderly Task Force guidelines for the use of colony-stimulating factors in elderly patients with cancer. Eur J Cancer 2003; 39: 2264–2272.[CrossRef][Medline]
30. Extermann M, Chen H, Cantor AB et al. Predictors of tolerance to chemotherapy in older cancer patients: a prospective pilot study. Eur J Cancer 2002; 38: 1466–1473.[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. Crivellari, M. Aapro, R. Leonard, G. von Minckwitz, E. Brain, A. Goldhirsch, A. Veronesi, and H. Muss Breast Cancer in the Elderly J. Clin. Oncol., May 10, 2007; 25(14): 1882 - 1890. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||