Significance of age and comorbidity on treatment modality, treatment adherence, and prognosis in elderly ovarian cancer patients
Highlights
► Age ≥ 70 and comorbidity highly influence whether patients are offered surgery and standard chemotherapy (CT). ► In patients treated with standard CT, neither age ≥ 70 nor comorbidity, influences ability of adhering fully to treatment. ► Age ≥ 70 and comorbidity are associated with poor survival, but with time-varying effect.
Introduction
Epithelial ovarian cancer (EOC) is the leading cause of death from gynaecologic cancer in the western world [1]. In Denmark the incidence of EOC has been rather stable during the past 20 years with approximately 580 new cases per year. The incidence and mortality of EOC increases with age and both peak at 75–79 years [2].
Age itself has been found to be a poor prognostic factor in patients with EOC [3], [4], [5], [6]. The reasons are not fully clarified. It could be factors such as comorbidity, more advanced stage at diagnosis, toxic effects of chemotherapy or that the elderly patients are withheld optimal surgery or chemotherapy.
The recommended treatment of EOC is upfront CRS and for all patients, except those with FIGO stage IA–IB grade 1 disease, followed by combination chemotherapy with carboplatin and a taxane (TC), 6 cycles administered every t3 weeks. In primary inoperable patients, three courses of neoadjuvant chemotherapy followed by interval debulking and then followed by another three courses of chemotherapy is an option. This treatment became standard after the GOG-111 and OV-10 both finding paclitaxel to be more effective than cyclophosphamide in combination therapy with cisplatin, and a meta-analysis of 37 randomised trials concluding that cisplatin and carboplatin are therapeutically equivalent in treatment of women with advanced EOC [7], [8], [9], [10]. Finally, TC was shown to be as effective as and less toxic than cisplatin and paclitaxel [11], [12], [13]. In these studies, however, median age did not exceed 60 years. Clinical trials directed specifically towards elderly cancer patients are scarce, and except for small-scale phase II trials, non‐existing for ovarian cancer.
The objectives of this study were to evaluate the significance of comorbidity and age on receiving cytoreductive surgery, standard combination chemotherapy (TC) , adherence to TC treatment, and finally, to estimate progression-free and overall 5-year survival.
Section snippets
Material and methods
The study is a retrospective cohort study. All Danish women who had a diagnosis of epithelial cancer of the ovaries or peritoneum in Denmark in 2005 and 2006 were included in the study. Data on these women were obtained from The Danish Gynecological Cancer Database (DGCD), The Danish Cancer Register (DCR), the Danish Causes of Death Register (DCDR), the National Register of Persons (NRP), and from the medical charts of the patients. Linkage of all data sources was performed via the personal
Results
We identified 979 patients in the DGCD with an incident diagnosis of cancer of the ovaries or peritoneum from January 1, 2005 to December 31, 2006. Of these, 18 were excluded: two were found not to have OC and 16 did not have epithelial OC.
A further 228 patients were identified in the DCR (Fig. 1). After manual review (by the DGCD), 83 of these could be excluded, either because they did not have EOC, or because they were registered in the DGCD as having a first time diagnosis of OC either
All patients
Of 961 patients, 629 (65%) had died at the end of the study period; of these, 554 (88%) died from progressive disease, 35 (6%) died within 30 days after surgery, and four patients (1%) died from acute toxicity. Twenty-one patients (3%) died from causes not related to the cancer disease and 15 patients (2%) died from unknown causes. Median overall survival (OS) of all women < 70 and ≥ 70 years was 50 and 18 months, respectively (log-rank test: P < 0.0001. Median progression-free survival (PFS) was 19
Discussion
In this study, we found that ovarian cancer patients aged ≥ 70 years are at a much higher risk of being excluded from surgical or medical therapy. These patients had a higher ASA score and they more often presented with advanced disease. When operated, they were less often optimally debulked. When treated according to the chemotherapy guidelines, elderly patients more often had dose reductions and discontinued treatment early. Although younger patients had a better prognosis, elderly benefited
Conflict of interest statement
The authors declare that there are no conflicts of interest. The work was supported by the Danish Cancer Society, the I.M. Daehnfeldt Foundation, and The Danish Health Insurance Foundation. The sponsors of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Acknowledgements
We would like to thank all who contributed to this work. Especially, we would like to thank Karina Dahl Steffensen, MD, PhD and Yvette Schandorf Sørensen, RN, both from Vejle Hospital for their help with the data collection.
References (34)
- et al.
The influence of age and co-morbidity on treatment and prognosis of ovarian cancer: a population-based study
Gynecol Oncol
(2005) - et al.
Feasibility, toxicity and quality of life of first-line chemotherapy with platinum/paclitaxel in elderly patients aged > or = 70 years with advanced ovarian cancer—a study by the AGO OVAR Germany
Ann Oncol
(2007) - et al.
Ovarian cancer in the octogenarian: does the paradigm of aggressive cytoreductive surgery and chemotherapy still apply?
Gynecol Oncol
(2008) - et al.
Single agents should be administered in preference to combination chemotherapy for the treatment of patients over 70 years of age with advanced ovarian carcinoma
Eur J Cancer
(2000) - et al.
Improved tolerance of primary chemotherapy with reduced-dose carboplatin and paclitaxel in elderly ovarian cancer patients
Gynecol Oncol
(2008) - et al.
A phase II study of weekly carboplatin and paclitaxel as first-line treatment of elderly patients with advanced ovarian cancer. A Multicentre Italian Trial in Ovarian cancer (MITO-5) study
Crit Rev Oncol Hematol
(2008) - et al.
Morbidity, mortality and overall survival in elderly women undergoing primary surgical debulking for ovarian cancer: a delicate balance requiring individualization
Gynecol Oncol
(2011) Survival and prognostic factors in patients with ovarian cancer
Obstet Gynecol
(2003)- et al.
Global cancer statistics
CA Cancer J Clin
(2011) - et al.
NORDCAN: cancer incidence, mortality, prevalence and survival in the Nordic countries, version 5.1
(March 2012)
Ovarian cancer in younger vs older women: a population-based analysis
Br J Cancer
Epithelial ovarian carcinoma in younger vs older women: is age an independent prognostic factor? The Hellenic Oncology Cooperative Group experience
Int J Gynecol Cancer
Prognostic factors for stage III epithelial ovarian cancer: a Gynecologic Oncology Group Study
J Clin Oncol
Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer
N Engl J Med
Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results
J Natl Cancer Inst
Chemotherapy in advanced ovarian cancer: four systematic meta-analyses of individual patient data from 37 randomized trials. Advanced Ovarian Cancer Trialists' Group
Br J Cancer
Gynecologic Cancer InterGroup (GCIG) consensus statement on clinical trials in ovarian cancer: report from the Fourth Ovarian Cancer Consensus Conference
Int J Gynecol Cancer
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