Each year, ovarian cancer affects more than 23,000 women and accounts for approximately 14,000 deaths in the US.¹ In Western and Northern Europe, as well as in the US, it is the fifth leading cause of cancer death among women and is the most deadly of the gynaecologic malignancies.² Although the annual incidence of ovarian cancer is only 17 cases per 100,000 women overall, the incidence is much higher in older women, with a peak age-adjusted rate of 54 per 100,000 in women 75 to 79 years old.³ The median age at diagnosis is 61 years.¹ Patients with familial ovarian cancer – which represents about 5% to 10% of cases – tend to be diagnosed almost a decade earlier.

Approximately 70% of women present with advanced disease. Favourable prognostic factors include young age, cell type other than clear cell or mucinous, lower stage, good performance status, small residual tumour volume and absence of ascites^.4,5 Of note, patients with BRCA1 mutations may have a more favourable prognosis than those without this mutation.⁶

First-line Therapy

The combination of cisplatin 75mg/m2 plus paclitaxel 135mg/m2 intravenously (IV) as a 24- hour continuous infusion was established as firstline therapy for advanced ovarian cancer in the mid- 1990s after a large, phase III Gynecologic Oncology Group (GOG) trial demonstrated superior results with this combination versus the then-standard regimen of cyclophosphamide and cisplatin.⁷
A number of studies have evaluated the combination of paclitaxel and carboplatin as an alternative to the paclitaxel and cisplatin regimen.^8–10 There were no differences observed between the two groups in terms of progression-free survival or overall survival. The paclitaxel/carboplatin regimen appears to be more attractive because it is associated with a lower incidence of non-haematologic toxicities (particularly neurotoxicity), and it allows for out-patient administration. In addition, patients treated in the paclitaxel/carboplatin arm had a significantly better quality–of–life.⁹ Following the release of the 2004 consensus statement on the management of ovarian cancer at the Third International Gynecologic Cancer Intergroup Ovarian Cancer Consensus Conference, the recommended first-line therapy is now the combination of carboplatin (AUC 5–7.5) and paclitaxel 175mg/m2/3h infusion given every week for six cycles.¹¹

The US National Cancer Institute (NCI) recently issued an announcement recommending that,“After primary surgery, women with optimally-debulked FIGO stage III ovarian cancer should be counselled about the clinical benefit associated with combined IV and intraperitoneal (IP) administration of chemotherapy. Based on the most recent trials, strong consideration should be given to a regimen containing IP cisplatin (100mg/m2) and a taxane, whether given by an IV only or IV plus IP.” According to the NCI, IP chemotherapy allows higher doses and more frequent administration of drugs, and it appears to be more effective in killing cancer cells in the peritoneal cavity, where ovarian cancer is likely to spread or recur first.¹² However, this announcement has become a topic of great debate in ovarian cancer.

Whatever the route of administration, most will respond to initial therapy; however, the relapse rate is high, and the five-year survival of patients with advanced disease is 25% –35%.^13,14

Disease Surveillance and Relapse Definition

Surveillance recommendations for monitoring disease activity during follow-up include physical examination with a thorough pelvic exam and serum tumour marker CA125 sampling. Clinical and serological exams are repeated at three-month intervals for two years, thereafter every six months for up to five years, and thereafter every 12 months until death of the patient.

Studies such as radiographic, computed tomography and magnetic resonance imaging are not costeffective and should not be systematically performed during follow-up. Imaging studies depend on clinical indication and are indicated to detect any lesion when relapse is suspected on the basis of clinical exam or an elevation of CA125 level.

Traditional clinical measures of relapse include disease progression according to RECIST criteria, defined as the appearance of any new measurable or non-measurable lesion or a 20% increase in sum of lesion longest diameters compared to lowest sum while on follow-up or a significant increase in nonmeasurable lesion such as ascites or pleural effusion. ¹⁵

The high frequency with which CA125 level increases before the appearance of detectable lesion has prompted the Gynecogic Cancer Intergroup (GCIG) to propose a progression definition complementary to RECIST that includes CA125 kinetics.16 According to GCIG criteria, relapse based on CA125 is defined by at least a doubling of CA125 level compared to nadir value observed during follow-up or to upper limit of normal when CA125 has previously normalized.CA125 doubling has to be confirmed at any time, but normally not less than one week after the first elevated level. CA125 levels sampled within four weeks after surgery, paracentesis or radiation therapy should not be taken into account since their elevation at these times may be spurious. In some instances, patients do not fare well.

The GOG has also proposed that health status deterioration is attributable to the disease as a criteria of progression, because some patients have clinical evidence of disease progression, without meeting the progression criteria previously defined.