ANTICANCER RESEARCH 27: 611-618 (2007)

Advanced Epithelial Ovarian Cancer in the Elderly: Chemotherapy Tolerance and Outcome ELENI EFSTATHIOU1, MELETIOS A. DIMOPOULOS1, GEORGE BOZAS1, EFSTATHIOS KASTRITIS1, LIA A. MOULOPOULOS2, ALEXANDROS RODOLAKIS3, GEORGE VLAHOS3, DIMITRA GIKA1, CHRISTOS PAPADIMITRIOU1 and ARISTOTELIS BAMIAS1 1Department

3First

of Clinical Therapeutics, 2Department of Radiology and Department of Obstetrics and Gynaecology, Athens University School of Medicine, Athens, Greece

Abstract. Background: The prognostic significance of age in ovarian cancer has not been clarified. We investigated the characteristics of ovarian cancer presenting in ages >70 years and assessed the prognostic significance of advanced age. Patients and Methods: Four hundred and fifty-three patients with stage IIC-IV ovarian cancer (age>70 years n=106 [23%]), treated postoperatively with platinum-based chemotherapy were retrospectively reviewed. Results: Median overall survival (OS) of patients ≤70 years old (52.3 months, 95% CI: 43.2-61.3) was longer than that of older patients (38.8 months, 95% CI: 29.9-47.7) (p=0.005), but this difference was not significant in a multivariate analysis (p=0.978). Age >70 years was correlated with worse performance status (PS) (p=0.019), higher tumor grade (p=0.033), residual disease >2 cm (p=0.006) and less frequent paclitaxel administration (p70 years. Patients who received their first course of chemotherapy up to June 2004 were included, in order to ensure at least one year of follow-up, since our database was updated in June 2005. All patients were older than 18 years, with histologically or cytologically proven EOC. Patients with borderline or germ cell tumors were excluded from the analysis. Creatinine clearance was

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ANTICANCER RESEARCH 27: 611-618 (2007) calculated according the Cockroft Formula (18), while carboplatin dose was calculated according to the Calvert formula (19). Staging was performed according to the FIGO staging system. Residual disease after surgical debulking was recorded according to the assessment by the surgeon. Tumor grading and histology were determined according to current FIGO guidelines. Performance status was evaluated according to the ECOG standards immediately before the initiation of chemotherapy. Following surgery, all patients received platinum-based chemotherapy. After the completion of chemotherapy, follow-up included a clinical examination and serum CA125 assay quarterly for the first two years, biannually for the following 3 years and annually thereafter. Chest X-ray and CT scan of the abdomen and the pelvis were performed every 6 months for the first 5 years and annually thereafter. Investigations were performed earlier if clinically indicated. Efficacy and toxicity analysis. Survival was calculated from the day of the initiation of treatment until date of death or last contact for patients still alive at the time of follow-up. In an intention-to-treat analysis all patients were included in survival analysis. Patients with bidimensionally measurable disease and having at least one followup tumor assessment were eligible for response evaluation. Standard WHO criteria (20) were used for classifying response. Toxicity was evaluated at each chemotherapy visit according to National Cancer Institute Common Toxicity Criteria. All patients who received at least one cycle of chemotherapy were included in the toxicity analysis. Relative dose intensity (RDI) was defined as the percentage of the expected dose administered to the patient (per unit of time expressed in mg/m2/week). Statistical analysis. All analyses were performed using the SPSS statistical software (SPSS for Windows, version 10, SPSS Inc., Chicago, IL, USA). Frequency distributions were used to describe the categorical variables, whereas continuous variables were presented as means and standard deviations. Differences across treatment arms regarding all categorical variables were examined with a ¯2 test whereas the Student’s t-test was used to test the equality of the appropriate means for continuous variables. The independent significance of the association of baseline characteristics with the age groups was tested using logistic regression analysis. Survival curves were produced with the Kaplan Meier method (21) and compared between arms with the log-rank test. For univariate and multivariate analyses of survival, the Cox proportional hazards model was used (22). Factors with a p-value 2 cm Histology Serous Endometroid Mucinous Clear cell Poorly-differentiated Non-specified Other Baseline Hb Median (range) First-line chemotherapy CyP CyC TP TPE ITP TC C TPA

≤70 N (%)

>70 N (%)

347 (76.6)

106 (23.4)

57 (37-70)

P*

75 (70-95) 2 cm, p0, stage IV and mucinous or clear cell type were independently associated with inferior survival (Table IV). Residual disease (p70 years of age. Univariate analysis showed that

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Table IV. Univariate and multivariate analysis of factors associated with survival. MS (95% CI) Univariate (months) Age >70 (n=105) ≤70 (n=347) Stage Stage IIC, III (n=373) Stage IV (n=79) ECOG PS PS=0 (n=288) PS≥1 (n=164) Residual 0-2 cm (n=114) >2 cm (n=337) Histology M+C (n=44) Other (n=407) Paclitaxel No (n=41) Yes (n=409)

38.8 (29.9-47.7) 52.3 (43.2-61.3)

P

Multivariate HR (95% CI)

P

0.005 1 1 (0.73-1.37)

0.978

52.7 (44.7-60.7)