OC is a relatively chemosensitive tumor in first-line setting. The current standard of first-line chemotherapy in advanced OC has evolved in the recent years from cyclophosphamide-based regimens to the combination of carboplatin AUC 5 and paclitaxel 175 mg/m² [13–17].

In elderly patients, as in younger patients, chemotherapy has a strong impact on OS. According to the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, survival improved by 38 % in treated elderly women, a rate similar to the benefits described in randomized controlled trials among younger patients [18]. Yet, only about half of the patients were treated with platinum-based chemotherapy [18]. This supposed undertreatment has also been reported in other retrospective cohorts of elderly patients not receiving any chemotherapy in 17–29 % of cases [19, 20].

Factors associated with decreased prescription of chemotherapy are age independently of comorbidities [21], and comorbidities [22].

Physicians often tend to reduce doses or prescribe partial courses of chemotherapy because older patients are more vulnerable to chemotherapy toxicities [23], particularly cytopenias and neuropathy [24]. As a consequence, dose intensity is not maintained and prognosis tends to worsen.

The most appropriate choice of agents is, as for their younger counterparts, a platinum-taxane doublet [7]. For older patients, several strategies have been evaluated to improve feasibility and tolerability while maintaining dose intensity. They are single-agent therapy with carboplatin, weekly schedules, and different chemotherapy timing (neoadjuvant chemotherapy).

Some authors consider that standard 3-weekly platinum/paclitaxel regimen is feasible in elderly patients [25]. Results from the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group 3 (AGO-OVAR-3) phase III trial [14] evaluating cisplatin/paclitaxel versus carboplatin/paclitaxel were retrospectively analyzed according to feasibility, toxicity, and quality of life in patients aged ≥70 years. Thirteen percent of enrolled patients in this trial were ≥70 years. Elderly patients received 98 %, 100 %, and 96 % of the recommended paclitaxel, carboplatin, and cisplatin dose, respectively, per cycle even though early discontinuation was more frequent in elderly patients. Quality of life and nonhematological and hematological toxicity were comparable between elderly and younger patients, except for febrile neutropenia (5 % versus <1 %, p = 0.005). In this older cohort, platinum/paclitaxel appeared to be feasible and tolerable. However, this population, treated under clinical trial conditions, was highly selected, and the results from this age-specific analysis basically give information about “fit” elderly patients.

Nonetheless, in routine practice, elderly patients are extremely heterogeneous [26]: some will tolerate chemotherapy as well as younger women (“fit patients”), while others will experience unpredictable and severe toxicity (“vulnerable patients”). To overcome this variability and therefore to identify patients at risk of severe toxicity, the French Groupe d’Investigateurs Nationaux pour l’Etude des Cancers Ovariens (GINECO) developed a program named “FAG” for “Femme ÂGée” (elderly woman in English) to assess tolerability and feasibility of standard front-line chemotherapy regimens enrolling unselected elderly patients (regardless of initial performance status and surgery status) while identifying geriatric parameters of interest.

The results of three age-specific prospective trials were successively reported:

Weekly dosing of paclitaxel and carboplatin has been evaluated in the phase II Multicenter Italian Trial in Ovarian cancer (MITO-5) study [30]. Eligible patients were ≥70 years but should have a PS ≤ 2. Patients received carboplatin (AUC 2) + paclitaxel (60 mg/m²) on days 1, 8, and 15 every 4 weeks, up to six cycles. Twenty-six patients were analyzed (median age 77 years, range 70–84). Fourteen patients had ≥2 comorbidities; 8 and 18 patients had some dependency in ADL or IADL, respectively. Twenty-three patients (88.5 %) were treated without suffering unacceptable toxicity. Median estimated progression-free survival was 13.6 months and median overall survival was 32.0 months. Similarly, the recent phase III MITO-7 trial’s results [31], which compared a weekly regimen to the standard 3-weekly regimen, showed similar progression-free survival (PFS) (18.3 versus 17.3 months, respectively) with less cytopenias, less neurotoxicity, and better quality of life scores. Even though age ≥70 showed no significant effect on PFS, PFS benefit with the weekly regimen was more important within the older-age-specific subgroup (HR: 0.70 [0.46–1.07]) (Table5.2).

Von Gruenigen et al. recently presented preliminary results of an elderly-specific prospective trial to study chemotherapy toxicity on quality of life in older patients with ovarian epithelial, primary peritoneal cavity, or fallopian tube cancer [32]. Patients and their physicians decided between regimen I (carboplatin AUC 5 and paclitaxel 135 mg/m² plus GCSF, every 3 weeks) and regimen II (carboplatin AUC 5 every 3 weeks) for 4 cycles either after primary surgery or as neoadjuvant chemotherapy. Two hundred and eight evaluable patients were enrolled onto regimen I (n = 149) or regimen II (n = 59). Completion rates were high (92 % versus 75 %). In the multivariate analysis, the inability to complete four cycles of chemotherapy was associated with regimen II (p < 0.001), neoadjuvant chemotherapy (p = 0.024), and limited social activities (p = 0.034), but not IADLs (p = 0.2). In both regimens, patient reported outcomes improved over time with cumulative chemotherapy cycles and at a similar pace. A third arm, evaluating weekly paclitaxel 60 mg/m² and carboplatin AUC 5 every 3 weeks, was added to the study. Final results are awaited (ClinicalTrials.gov identifier NCT01366183).

Other strategies have been evaluated in retrospective analysis such as reduced doses or addition of a third cytotoxic agent.

Reduced doses were evaluated in a retrospective cohort [33]. Patients received carboplatin AUC 4–5 and paclitaxel 135 mg/m². Twenty-six patients treated with reduced doses (RD) were compared to 74 patients treated with standard doses (SD). Median age was 77.0 in the RD group. Incidence of grade 3–4 neutropenia was higher in the SD group (54.1 % versus 19.2 %; p = 0.002). SD patients were more likely to experience cumulative toxicity (p = 0.003) and required delays in treatment schedule (p = 0.05). There were no differences in PFS or OS between cohorts.

Compared with standard paclitaxel and carboplatin, addition of a third cytotoxic agent such as gemcitabine, topotecan, or pegylated liposomal doxorubicin (PLD) provided a small benefit in PFS (1 month) but a shorter OS (37 versus 45 months) and increased toxicity (cytopenias and neurotoxicity) in a retrospective analysis of 620 elderly patients included in the Gynecologic Oncology Group (GOG) 182 phase III trial [24, 34].

Concerning the addition of antiangiogenic agents to front-line chemotherapy, no age-specific trials are available. Yet, in the GOG 218 randomized phase III trial, the effect in terms of improvement of PFS was seen consistently in all the prognostic subgroups including the age subgroup [39]. However, bevacizumab use requires more caution in the elderly due to more frequent grade ≥3 toxicity and more vascular events (8.5 % arterial thromboembolic events in patients older than 65 compared to 2.9 % in younger patients) [40]. Comorbidities and associated risk factors such as personal history of hypertension, stroke or transient ischemic attack, etc. must be carefully evaluated prior to prescription, and patients must be closely monitored.

Use of neoadjuvant therapy has increased over time particularly in old and frail patients [41]. Indeed, cytoreductive surgery (CRS) is associated with substantial postoperative morbidity [42], and there are several issues concerning chemotherapy delivery following surgery with significant delays in the initiation of chemotherapy [43]. Neoadjuvant chemotherapy, on the other hand, reduces the burden of surgical procedure, increases rates of optimal CRS [44], and reduces perioperative morbidity and mortality [45].