Considerations in Recurrent Ovarian Cancer

The Aims of Treatment at Relapse

Because salvage treatments are rarely curative, treatment at relapse has long been considered as solely palliative, without consideration of patient survival. Recent results of randomized studies showing improving survival in some subsets of patients has prompted a review of treatment goals at relapse. These have been redefined at the 3rd Consensus Conference on Ovarian Cancer recently held in Baden-Baden, Germany, in September 2004.8 The main goals of treatment of patients with relapsing ovarian cancer are to provide disease control, i.e. survival prolongation, together with symptom palliation and an emphasis on patient quality-of-life. However, considerations must be taken into account for patients who are platinumresistant compared to platinum-sensitive patients.

Prognostic Factors: the Importance of Therapy-free Interval

The choice of second-line therapy largely depends upon the interval from the completion of platinumbased first-line therapy to relapse. Patients who progress on first-line platinum therapy are said to have platinum-refractory disease; those who relapse within six months are considered to have platinumresistant disease; and those with a relapse-free interval of at least six months are said to have potentially platinum-sensitive disease.

The probability of a response to a platinum-based regimen depends upon the length of the interval between first-line platinum therapy and relapse. In a study of 82 patients with relapsed disease, a longer cisplatin-free interval was associated with higher response rates.¹⁷ Patients with a cisplatin-free interval of five to 12 months had a 27% response rate, those with a cisplatin-free interval of 13 to 24 months had a 33% response rate and those with a cisplatin-free interval of more than 24 months had a response rate of 59%. Furthermore, patients who had not received any treatment (including non-cisplatin regimens) for more than 24 months from the time of initial cisplatin-based therapy had a response rate of 77%.The importance of the therapy-free interval in the outcome has been recently confirmed in a large GINECO study of 583 patients in relapse (seeTable 1).¹⁸

One explanation for the consistent relationship between tumour response and platinum- or treatmentfree interval is tumour resistance. In acquired resistance, tumours become resistant to multiple drugs under the selective pressure of a specific agent. However, the acquired resistance is frequently unstable and can be lost over time. Therefore, the longer the treatment-free interval, the greater the chance of tumours to lose acquired resistance.

Other prognostic factors include the size of detectable tumours (> or <5cm), the number of tumour sites and patient performance status.