Prognostic impact of the time interval between surgery and chemotherapy in advanced ovarian cancer: analysis of prospective randomised phase III trials

Abstract

Background and aims: Surgery followed by platinum-taxane chemotherapy is the current standard approach to treat advanced ovarian cancer. The impact of the time interval between surgery and initiation of chemotherapy for clinical outcome has not been clarified yet.

Methods: Individual patient data analysis of 3326 patients from three prospective randomised phase III trials conducted between 1995 and 2002 to investigate platinum-taxane based chemotherapy regimens in advanced ovarian cancer. Time to chemotherapy (TTC) was analysed and correlated with outcome.

Results: Median TTC was 19 days (range 1-56). The effect of TTC differed significantly for patients with or without residual disease for progression-free (PFS; interaction p=0.004) and for overall survival (OS; interaction p=0.028). A delayed start of chemotherapy was associated with earlier disease recurrence (HR 1.038, 95% CI 0.973; 1.106, p=0.257 per week delay) and a significantly decreased OS (HR 1.087, 95% CI 1.005; 1.176 p=0.038) in patients with no residual tumour after surgery. In contrast, in patients with residual disease, a longer TTC was significantly associated with later progression (HR 0.931, 95% CI 0.895; 0.969, p<0.001) and no effect towards OS (HR 0.983, 95% CI 0.940; 1.028, p=0.452).

Conclusions: Our results provide evidence that early initiation of chemotherapy might result in slightly improved survival in patients with complete cytoreduction while patients with residual disease after surgery did not benefit from earlier chemotherapy. A prospective study randomising patients to different time intervals could clarify the definitive relevance of the time between surgery and chemotherapy.