Annals of Oncology Advance Access originally published online on November 2, 2006
Annals of Oncology 2007 18(2):256-262; doi:10.1093/annonc/mdl400
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2006 European Society for Medical Oncology
gynecologic tumors |
Carboplatin/cyclophosphamide or carboplatin/paclitaxel in elderly patients with advanced ovarian cancer? Analysis of two consecutive trials from the Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens
1 Medical Oncology Department, Hospices Civils de Lyon et Université de Lyon
2 Medical Oncology Department Hôtel Dieu, Paris
3 Department of Medical Information, Hospices Civils de Lyon, Lyon
4 Department of Medical Oncology, Centre Paul Papin, Angers
5 Department of Medical Oncology, Centre Alexis Vautrin, Nancy
6 Department of Medical Oncology, Clinique Rochebelle, Alès
7 Department of Medical Oncology, Centre Hospitalier, Annecy
8 Department of Medical Oncology, Centre Hospitalier, Limoges
9 Department of Medical Oncology, Centre Hospitalier Michallon, Grenoble, France
* Correspondence to: Dr G. Freyer, Medical Oncology Department, Centre Hospitalier Lyon Sud, 69495 Pierre-Bénite Cedex, France. Tel: +33-0-478864318; Fax: +33-0-478864319; E-mail: gilles.freyer{at}chu-lyon.fr
 |
Abstract |
|---|
 Top Abstract introductionpatients and methodsresultsdiscussionAcknowledgementsReferences |
|---|
Background: To determine the feasibility of two chemotherapy regimens in elderly patients with advanced ovarian carcinoma (AOC).
Patients and methods: Eighty-three patients 
70 years were previously enrolled in a trial evaluating carboplatin and cyclophosphamide (CC). On the basis of identical eligibility criteria, 75 further patients were enrolled in a trial evaluating carboplatin and paclitaxel (Taxol) (CP). The primary end point of these studies was the feasibility of six courses of chemotherapy. Comprehensive geriatric assessment (CGA) parameters were assessed in terms of prognostic factors.
Results: More patients in the CC group presented with performance status of two or more, depression symptoms, use of co-medications, hypoalbuminemia, abnormal Mini-Mental Status score, or sub-optimal surgery. Both regimens appeared feasible: 75.6% in the CC group and 68.1% in the CP group completed six courses. CC and CP groups had similar overall survival (OS). Independent prognostic factors of poorer OS were the following: increasing age (P = 0.013), depression symptoms at baseline (P < 0.001), International Federation of Gynecology and Obstetrics stage IV (P = 0.001), and use of paclitaxel (P = 0.025).
Conclusion: As this is a non-randomised retrospective review of two consecutive studies, no firm conclusion can be drawn. It seems, however, that in elderly patients with AOC the use of paclitaxel results in more toxicity. CGA parameters and particularly emotional disorders might help to determine a priori the risk/benefit ratio of chemotherapy in this patient population.
Key words: carboplatin, comprehensive geriatric assessment, elderly, ovarian cancer, paclitaxel
|
introduction |
|---|
|
TopAbstractintroductionpatients and methodsresultsdiscussionAcknowledgementsReferences |
|---|
The incidence of ovarian cancer increases with age, peaking in the seventh decade of life, and remains elevated until age 80 years. The survival rates at 1-year decreases with age for almost all cancers sites. For ovarian cancer, the age-standardised relative survival rates at 1 year are 57% in the age group of 65–69 years, 45% in the age group of 70–74 years, and 33% for the age group of 80–84 years [1].
Despite recent advances in ovarian cancer therapy, physicians have been reluctant to enrol elderly patients on to clinical trials [2]. This could be explained by the heterogeneity of this population and higher risk of dying from co-morbid conditions. Prospective trials on elderly patients should take into account comprehensive geriatric assessment (CGA) parameters in order to predict efficacy and tolerance of treatment. We showed previously that CGA could predict severe toxicity and overall survival (OS) of advanced ovarian carcinoma (AOC) patients above the age of 70 years using the carboplatin and cyclophosphamide (CC) combination [3].
Carboplatin has demonstrated single-agent efficacy in AOC and has been the cornerstone for most combination regimens [4]. Carboplatin and paclitaxel (CP) has become the standard for first-line treatment of AOC in most countries [5–8]. However, few data are available about the tolerance of CP in ovarian cancer patients 70 years [9]. We therefore conducted a multicentre prospective trial in order to assess the safety of this standard combination in patients 70 years with stage III/IV epithelial carcinoma of the ovary.
Here we analyse the results of the two prospective trials conducted successively by our group of investigators in order to address whether the CP has a favourable or unfavourable effect on tolerance and OS in elderly women with AOC, in comparison with the CC regimen.
|
patients and methods |
|---|
|
TopAbstractintroductionpatients and methodsresultsdiscussionAcknowledgementsReferences |
|---|
study design
From 1998 to 2000 the Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO) enrolled 83 patients
70 years with AOC in 30 centres to investigate the CC combination: the CC group [3]. From 2001 to 2004, we used the same study design to enrol chemo-naive patients in a new open-label multicentre prospective trial to investigate the CP combination: the CP group. The Independent Ethics Committee of Lyon University Hospital approved each study protocol before commencement. Written informed consent was obtained from each patient.
The primary end point of this study was to assess the feasibility of the regimens, defined as the completion of six courses of chemotherapy without disease progression, death due to any cause, or investigator's or patient's decision to stop treatment because of chemotherapy-related toxicity. Chemotherapy was considered non-feasible if discontinuation of treatment was necessary because of toxicity despite dose reduction. Secondary objectives included assessment of chemotherapy-induced side effects and the ability of some CGA parameters to predict tolerance and OS.
eligibility criteria
Eligibility criteria in both studies were similar: we included patients 70 years with stage III or IV ovarian epithelial carcinoma with a life expectancy of at least 3 months and normal blood parameters [laboratory quantities were as follows: neutrophils 1.5 x 109/l, platelets 100 x 109/l, rise in serum bilirubin level <2x the upper limit of normal (ULN), alanine aminotransferase (ALT), aspartate aminotransferase (AST) <2 x ULN, and/or alkaline phosphatase (ALP) <3 x ULN]. Patients were ineligible if they had prior malignancy (excluding carcinoma in situ of the uterine cervix or urinary bladder, or basal cell carcinoma), prior chemotherapy or radiotherapy, serious medical or psychiatric illness that could affect the treatment, congestive heart failure, and history of hypersensitivity to Cremophor EL (Bristol-Myers-Squibb Co., Princeton, NJ) in the CP group.
treatment
In the CC group, patients received carboplatin AUC (area under the curve for drug concentration as a function of time) = 5 mg·min/ml and cyclophosphamide 600 mg/m2 every 4 weeks [3]. In the CP group, carboplatin AUC = 5 mg·min/ml and paclitaxel (Taxol; Bristol-Myers-Squibb Co., Princeton, NJ) 175 mg/m2 were administered each 3-week cycle. Patients received premedication before paclitaxel infusion with 20 mg of i.v. dexamethasone, 5 mg i.v. dexchlorpheniramine, and 300 mg i.v. cimetidine or 50 mg i.v. ranitidine. Antiemetics were given i.v.: ondansetron 8 mg or granisteron 3 mg. Subsequent premedication was used when clinically indicated. Patients continued therapy for up to six cycles. After six cycles, the investigator was allowed to prolong chemotherapy for three more courses if there was tumour response or stabilisation.
comprehensive geriatric assessment
Patients were checked by medical history for co-morbidity including atherosclerosis, congestive heart failure, hypertension, chronic obstructive pulmonary disease, diabetes mellitus type 1 or 2, and chronic renal insufficiency. Pre-treatment evaluation included Eastern Cooperative Oncology Group (ECOG) performance status (PS), body mass index (BMI), and haematology and blood chemistry (complete blood counts, haemoglobin, AST, ALT, ALP, 
-glutamyltransferase, rise in bilirubin level, blood electrolytes, serum creatinine level and urea, total serum cholesterol value, and CA 125 assay). Screening also comprised electrocardiogram and computed tomography scans of the chest, abdomen, and pelvis.
We carried out the CGA at study entry. It included evaluation of patient dependence, co-medication defined as the number of different drugs taken daily: 0–3, 4–6 or >6, nutritional status (total protein, albumin, prealbumin, C-reactive protein, and orosomucoid), and cognitive function using the Mini-Mental Status (MMS). We defined a MMS score of 24–30 as ‘normal’ and regarded a score <24 as an indicator of cognitive dysfunction [10]. Presence or absence of clinical symptoms of depression was evaluated in a similar way by the investigator for both groups. In the CP group, we recorded the Instrumental Activities of Daily Living (IADL) and the Hospital Anxiety and Depression Scale (HADS). The IADL includes nine skills a person needs to live independently [11]. The HADS is a brief widely used self-report assessment tool of anxiety and depression, ranging from 0 (no problem) to 42 (maximum emotional distress) [12].
evaluation criteria for toxicity
Complete blood count was carried out before each cycle of chemotherapy. Toxic effects were assessed before each new treatment cycle and graded according to the National Cancer Institute Common Toxicity Criteria version 2.0. Dose reductions of chemotherapy were planned for neutropenia <0.5 x 109/l lasting >7 days, neutropenia <0.1 x 109/l lasting >3 days, febrile neutropenia, thrombocytopenia <10 x 109/l, incomplete haematological recovery at day 29 (neutrophils <1.5 x 109/l and platelets <100 x 109/l), grade 3 stomatitis, or grade 3 neurotoxicity. The carboplatin dose was reduced to an AUC 4, the cyclophosphamide dose to 500 mg/m2 and the paclitaxel dose to 150 mg/m2 for the first dose reduction. A second dose reduction was allowed for the CP group with carboplatin AUC 4 and paclitaxel 135 mg/m2.
statistical considerations
number of patients to be included in the study.
Assuming an estimated end point frequency in the CC group of 76% [3], we calculated that 70 patients would be required for the CP group to have 80% power to detect a 30% reduction in the relative risk with a two-sided alpha level of 5%.
patients' characteristics, CGA parameters, and toxic effects.
We summarised data as means with standard deviations (SDs) for continuous variables and as numbers (percentages) of patients for categorical variables. To compare the baseline characteristics of the two groups in univariate analyses, we used the Pearson's chi-square or Fisher's exact test, as appropriate, for categorical variables and the Student's t-test for continuous variables.
survival analysis.
We calculated duration of survival from the date of inclusion to the date of death from any cause. Survivors were censored at the date they were last known to be alive. OS was estimated using the Kaplan–Meier method with censored data. Comparisons were estimated by use of log-rank test. In order to assess the effects of covariates (i.e. the patients' characteristics and CGA parameters) on OS, we used the proportional hazards model, adjusted on the treatment combination, to test each covariate (data not shown). A final model was obtained by stepwise introduction of covariates that had been significantly associated with OS with a P value <0.10.
All tests were two sided. Analyses were carried out using the SPSS® version 11.0 statistical package (SPSS Inc., Chicago, IL).
|
results |
|---|
|
TopAbstractintroductionpatients and methodsresultsdiscussionAcknowledgementsReferences |
|---|
patients' characteristics
One hundred and fifty eight women above the age of 70 were included; 83 patients in the CC group from 7/1998 to 10/2000 and 75 patients in the CP group from 9/2001 to 4/2004. Three patients of the CP group were removed from the analysis due to non-epithelial histology, stage II epithelial carcinoma, and non-treated congestive heart failure. The characteristics of the 155 patients analysed are summarised in Table 1. The 83 patients of the CC group were treated in 30 centres. The 72 patients of the CP group were treated in 23 of these 30 centres. Respectively 10% and 4% of the patients of the CC and CP group did not undergo initial surgery; the diagnosis was made by cytological examination of pleural or peritoneal effusion.
|
Women in the CC group presented more often with a PS of two or more (P = 0.06) and were significantly less likely to have had optimal initial surgery as compared with the CP group. Histological type and International Federation of Gynecology and Obstetrics (FIGO) stage were similar.
comprehensive geriatric assessment
CGA parameters are shown in Table 2. Presence of clinical symptoms of depression, abnormal MMS score, and co-medications were more frequent in the CC group. Median BMI was 22.9 (SD = 4.05) and 23.1 (SD = 4.70) in the CC and CP group, respectively. Baseline hypoalbuminemia was less frequent in the CP group (P = 0.07). In this group, IADL and HADS data were available in 56 and 42 patients, respectively. At least one IADL dependency was reported in 38 patients (68%). The median HADS score was 12 (range = 4–30; SD = 5.8).
|
feasibility and safety
A total of 472 and 348 cycles were administered for the CC and CP group, respectively. One patient of the CC group was not evaluated for feasibility because of missing data. Sixty-two out of the 82 patients of the CC group [75.6%, 95% confidence interval (CI) 66% to 85%] and 49 out of 72 patients of the CP group (68.1%, 95% CI 57% to 79%) received six cycles of chemotherapy without severe toxicity or disease progression (P = 0.3). Both chemotherapy regimens appeared feasible, without any statistical difference between them.
Toxicity is summarised in Table 3. All 155 patients who received at least one dose of chemotherapy were evaluated for toxicity. Details of toxicity in the CC group have been reported previously [3]. For the CP group, 23 patients discontinued treatment before receiving six courses. Reasons were toxicity (15 patients), disease progression (seven patients), and withdrawal of consent (one patient). One patient died after febrile neutropenia during cycle 4.
|
Women in the CC group were less likely to experience neutropenia compared with the women treated by the CP combination (8.1% versus 52.8%, P < 0.001), but more likely to have reduced platelets (39.5% of patients with <50 x 109/l in this group versus 9.7% in the CP group, P <0.001). Low rates of grade 3–4 non-haematologic toxicity were observed for both regimens; except alopecia, neurosensory and neuromotor toxicity were worse with the CP regimen.
prognostic factors of OS
At the last update, 43% of the patients had died. Median OS for the entire population was 22.3 months (95% CI 15.1 to 29.5 months). Median OS was 21.6 months (95% CI 13.4 to 29.8 months) and 25.9 months (95% CI 17.4 to 34.5 months) for the CC and CP groups, respectively. Figure 1 shows OS by treatment group without adjustment for any prognostic factors. Adjustment for age, stage, and PS in a multivariable Cox regression model indicated that the risk of death was higher with the CP combination (P = 0.025, Table 4). In this multivariate analysis model, whereas the PS did not represent a significant independent predictor of mortality (P = 0.064), depressive symptoms at baseline appeared highly significant (P < 0.001).
|
|
Figure 2 shows OS curves for the patients of the CP group, the univariate analysis for 2-year OS showed that the total HADS (<15 versus
15) was a prognostic factor (
2 = 5.9; P = 0.015).
|
|
discussion |
|---|
|
TopAbstractintroductionpatients and methodsresultsdiscussionAcknowledgementsReferences |
|---|
This study is the first trial reporting the outcomes of two different types of chemotherapy for women more than 70 years of age with AOC. The patients were enrolled prospectively into two similar consecutive studies, on the basis of identical eligibility criteria. For the first trial, we used a well-tolerated chemotherapy [13] every 4 weeks. We decided to carry out the second trial with chemotherapy considered as a standard for first-line treatment [5–8] every 3 weeks. Consequently, this study is a retrospective evaluation of two different schedules of chemotherapy.
We observed better prognostic factors in the CP group (PS 0–1, less symptoms of depression, and less co-medications) than in the CC group. Because it is commonly believed that ‘frail’ elderly patients might not be able to tolerate aggressive treatment, physicians are often reluctant to administer paclitaxel-based chemotherapy to these patients. Furthermore, women in the CP group initially had a better rate of optimal cytoreduction surgery, which has been shown to be the strongest predictor of improved median survival even after controlling for age [14]. On the basis of these factors, we expected a better survival in the CP group, but we did not find added benefits in terms of OS in comparison with the use of the CC regimen. In the International Collaborative Ovarian Neoplasm Study 3 (ICON3) randomised trial, the authors found no clear evidence that the CP combination was more or less effective than single-agent carboplatin in any subgroup for effects on OS: the subgroup of patients 65 years experienced a similar number of events in both chemotherapy groups [4]. Even though the design and the conduction of this last study are controversial, its results and ours raise questions about use of paclitaxel for elderly patients with AOC. Given the rates of febrile neutropenia, the risk of cytotoxicity-induced death (one patient in the CP group died), and our observation that the CP regimen was not associated with improved survival, the CP combination for elderly patients with AOC must be considered with caution. But given the absence of randomisation, a definitive conclusion regarding the efficacy of this combination cannot be drawn in our study.
Despite the toxicity, we must emphasise that our data showed the CP regimen as a feasible treatment for elderly AOC. Several studies have indicated that the CP combination has an acceptable toxicity profile regardless of patient age [9, 15] with the caveat that the clinical trials included only a small number of elderly patients not older than 78 years of age. Older patients have diminished haematopoietic reserve, which may lead to increased susceptibility to chemotherapy-induced myelosuppression [16]. Uyar and colleagues' [17] analysis of data obtained from 131 women 70 years with ovarian cancer showed that haematologic toxicity increased with use of combination chemotherapy and with advancing age (47% of grade 3/4 haematologic toxicity for the age group 70–79 versus 79% for the age group 80, P = 0.006). In our study, the haematological toxicity was not similar between both groups, but the difference between both schedules of blood tests (every 4 weeks versus every 3 weeks) may have had underestimated this haematologic toxicity. However, we found that >50% and 8% of the women treated by the CP regimen had neutropenia grade 3/4 and febrile neutropenia, respectively. That is comparable with most of the prospective studies evaluating the CP combination in AOC [5–7]. du Bois and colleagues [5] reported an 8% rate of febrile neutropenia over all courses of CP treatment in patients with a median age of 56.7 years (range = 20.8–77.4). The CC regimen seems to be associated with greater rates of anaemia and thrombocytopenia, as reported by other investigators [13, 18]. These haematological toxic effects were, however, rarely associated with complications.
Studies by Begg and Carbone [19], Higgins et al. [9], and Villella et al. [20] suggest no difference in the incidence of neurotoxicity in older patients compared with younger ones. We observed grade 3 neurologic symptoms in 12% of our CP group, and this may have a serious impact on the patient's independence. Chen and colleagues [21] showed a significant decline of the IADL score in 60 patients 70 years who were undergoing cancer chemotherapy. The impact of neurotoxicity (especially in elderly patients) has been poorly characterised, and few investigators have used validated instruments. Hay [22], however, reported that chemotherapy regimens that cause less neuropathy in patients treated for ovarian cancer will have a positive impact on patient-assessed health status and quality of life.
We did not succeed in determining specific predictive factors associated with an increasing rate of toxicity. Extermann and colleagues [23] conducted a pilot prospective study to determine whether independent specific factors influencing toxicity could be identified for elderly patients. Baseline functional, emotional, and mental status did not correlate significantly with the occurrence of severe chemotherapy-related toxicity. In our previous report, among patients in the CC group who experienced severe toxicity necessitating treatment discontinuation, some variables such as depressive symptoms (P = 0.006), PS of two or more (P = 0.026), and dependence (P = 0.048) appeared to have independent predictive value [3]. Our failure to determine predictive factors for chemotherapy tolerance may be due to the high toxicity of the paclitaxel itself.
It is debatable to consider age as an independent prognostic factor for OS [24, 25], as shown in our study. In order to evaluate more precisely the role of age in OS, CGA parameters should be taken into account. Co-morbidity and functional impairments were shown to be independently associated with survival from cancer [26]. The ECOG PS, which is a basic measurement of functional ability, does not include many areas of impaired function commonly seen in elderly patients [27]. There is evidence that presence of functional disabilities increases with age, and more than half of elderly patients with various cancers have reduced IADL score [28]. A conclusion regarding outcomes in the patients with IADL dependency in this study cannot be drawn because of the small sample size of evaluable data.
Presence of symptoms of depression, assessed by the investigator, was an independent prognostic factor in the CC group [3] and remains independently associated with mortality in the current pooled analysis. Furthermore, the HADS score, which is widely used to screen for major depression and adjustment disorders in oncology patients [29, 30], is a prognostic factor of OS in the CP group. The association between mental health status and survival should be further investigated in patients with advanced cancer. ‘Psychological distress’ is a treatable condition which can be identified; the impact of a psychiatric intervention during cancer treatment should also be assessed.
CGA is probably the most widely available and useful assessment for the diagnosis of geriatric syndromes. Many manageable conditions (such as social problems, nutritional issues, and depression) can be identified in order to judge functional independence and to estimate tolerance of chemotherapy and probable survival. Our group is now planning to conduct a specific study to assess the value of psychosocial programs in elderly AOC patients who will be treated with a carboplatin-based chemotherapy but without any paclitaxel according to our present results.
|
Acknowledgements |
|---|
|
TopAbstractintroductionpatients and methodsresultsdiscussionAcknowledgementsReferences |
|---|
We thank Ian F. Tannock, from the Princess Margaret Hospital, Toronto, Canada, for his useful advice and careful reading of the report. We express our gratitude to all the members of the Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens Data Monitoring Center and in particular Christiane Dumont-Puléo, Bénédicte Votan, and Nathalie Le Fur. We are also grateful to the patients who participated in both studies.
Received for publication May 15, 2006. Revision received August 25, 2006. Accepted for publication September 18, 2006.
|
References |
|---|
|
TopAbstractintroductionpatients and methodsresultsdiscussionAcknowledgementsReferences |
|---|
1. Vercelli M, Capocaccia R, Quaglia A, et al. (2000) Relative survival in elderly European cancer patients: evidence for health care inequalities. The EUROCARE Working Group. Crit Rev Oncol Hematol 35:161–179.[Web of Science][Medline]
2. Lewis JH, Kilgore ML, Goldman DP, et al. (2003) Participation of patients 65 years of age or older in cancer clinical trials. J Clin Oncol 21:1383–1389.
3. Freyer G, Geay JF, Touzet S, et al. (2005) Comprehensive geriatric assessment predicts tolerance to chemotherapy and survival in elderly patients with advanced ovarian carcinoma: a GINECO study. Ann Oncol 16:1795–1800.
4. International Collaborative Ovarian Neoplasm Group. (2002) Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: the ICON3 randomised trial. Lancet 360:505–515.[CrossRef][Web of Science][Medline]
5. du Bois A, Luck HJ, Meier W, et al. (2003) A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst 95:1320–1329.
6. Ozols RF, Bundy BN, Greer BE, et al. (2003) Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol 21:3194–3200.
7. Vasey PA, Jayson GC, Gordon A, et al. (2004) Phase III randomized trial of docetaxel–carboplatin versus paclitaxel–carboplatin as first-line chemotherapy for ovarian carcinoma. J Natl Cancer Inst 96:1682–1691.
8. du Bois A, Quinn M, Thigpen T, et al. (2005) 2004 consensus statements on the management of ovarian cancer: final document of the 3rd International Gynecologic Cancer Intergroup Ovarian Cancer Consensus Conference (GCIG OCCC 2004). Ann Oncol 16:Suppl 8, viii7–viii12.
9. Higgins RV, Naumann RW, Gardner J, et al. (1999) Is age a barrier to the aggressive treatment of ovarian cancer with paclitaxel and carboplatin? Gynecol Oncol 75:464–467.[CrossRef][Web of Science][Medline]
10. Tombaugh TN and McIntyre NJ. (1992) The Mini-Mental State examination: a comprehensive review. J Am Geriatr Soc 40:922–935.[Web of Science][Medline]
11. Lawton MP and Brody EM. (1969) Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 9:179–186.[Web of Science][Medline]
12. Zigmond AS and Snaith RP. (1983) The hospital anxiety and depression scale. Acta Psychiatr Scand 67:361–370.[Web of Science][Medline]
13. Swenerton K, Jeffrey J, Stuart G, et al. (1992) Cisplatin–cyclophosphamide versus carboplatin–cyclophosphamide in advanced ovarian cancer: a randomized phase III study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 10:718–726.
14. Bristow RE, Tomacruz RS, Armstrong DK, et al. (2002) Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol 20:1248–1259.
15. Gronlund B, Hogdall C, Hansen HH, et al. (2002) Performance status rather than age is the key prognostic factor in second-line treatment of elderly patients with epithelial ovarian carcinoma. Cancer 94:1961–1967.[CrossRef][Web of Science][Medline]
16. Balducci L. (2003) Myelosuppression and its consequences in elderly patients with cancer. Oncology (Huntingt) 17:27–32.
17. Uyar D, Frasure HE, Markman M, et al. (2005) Treatment patterns by decade of life in elderly women (> or =70 years of age) with ovarian cancer. Gynecol Oncol 98:403–408.[CrossRef][Web of Science][Medline]
18. Meerpohl HG, Sauerbrei W, Kuhnle H, et al. (1997) Randomized study comparing carboplatin/cyclophosphamide and cisplatin/cyclophosphamide as first-line treatment in patients with stage III/IV epithelial ovarian cancer and small volume disease. German Ovarian Cancer Study Group (GOCA). Gynecol Oncol 66:75–84.[CrossRef][Web of Science][Medline]
19. Begg CB and Carbone PP. (1983) Clinical trials and drug toxicity in the elderly. The experience of the Eastern Cooperative Oncology Group. Cancer 52:1986–1992.[CrossRef][Web of Science][Medline]
20. Villella JA, Chaudhry T, Pearl ML, et al. (2002) Comparison of tolerance of combination carboplatin and paclitaxel chemotherapy by age in women with ovarian cancer. Gynecol Oncol 86:316–322.[CrossRef][Web of Science][Medline]
21. Chen H, Cantor A, Meyer J, et al. (2003) Can older cancer patients tolerate chemotherapy? A prospective pilot study. Cancer 97:1107–1114.[CrossRef][Web of Science][Medline]
22. Hay JW. (2002) Quality of life effects of chemotherapy-induced neuropathy in ovarian cancer. In: Proceedings of the 38th Annual Meeting of the American Society of Clinical Oncology. Proc Am Soc Clin Oncol, Orlando, FL (Abstr 886).
23. Extermann M, Chen H, Cantor AB, et al. (2002) Predictors of tolerance to chemotherapy in older cancer patients: a prospective pilot study. Eur J Cancer 38:1466–1473.[CrossRef][Web of Science][Medline]
24. Duska LR, Chang YC, Flynn CE, et al. (1999) Epithelial ovarian carcinoma in the reproductive age group. Cancer 85:2623–2629.[CrossRef][Web of Science][Medline]
25. Maas HA, Kruitwagen RF, Lemmens VE, et al. (2005) The influence of age and co-morbidity on treatment and prognosis of ovarian cancer: a population-based study. Gynecol Oncol 97:104–109.[CrossRef][Web of Science][Medline]
26. Extermann M, Overcash J, Lyman GH, et al. (1998) Comorbidity and functional status are independent in older cancer patients. J Clin Oncol 16:1582–1587.
27. Repetto L, Fratino L, Audisio RA, et al. (2002) 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 20:494–502.
28. Serraino D, Fratino L, Zagonel V. (2001) Prevalence of functional disability among elderly patients with cancer. Crit Rev Oncol Hematol 39:269–273.[Web of Science][Medline]
29. Razavi D, Delvaux N, Farvacques C, et al. (1990) Screening for adjustment disorders and major depressive disorders in cancer in-patients. Br J Psychiatry 156:79–83.
30. Ibbotson T, Maguire P, Selby P, et al. (1994) Screening for anxiety and depression in cancer patients: the effects of disease and treatment. Eur J Cancer 30a:37–40.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Smith, D. Su, I. A. Rigault de la Longrais, P. Schwartz, M. Puopolo, T. J. Rutherford, G. Mor, H. Yu, and D. Katsaros ERCC1 Genotype and Phenotype in Epithelial Ovarian Cancer Identify Patients Likely to Benefit From Paclitaxel Treatment in Addition to Platinum-Based Therapy J. Clin. Oncol., November 20, 2007; 25(33): 5172 - 5179. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P Zola and A Ferrero Is carboplatin-paclitaxel combination the standard treatment of elderly ovarian cancer patients? Ann. Onc., February 1, 2007; 18(2): 213 - 214. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||