Weekly cisplatin and daily oral etoposide is highly effective in platinum pretreated ovarian cancer

Abstract

We investigated the potential of weekly cisplatin and daily oral etoposide followed by oral etoposide maintenance therapy in patients with platinum-refractory ovarium cancer. One hundred and seven patients were entered on the study, 98 patients completed the induction therapy consisting of cisplatin at either 50 or 70 mg m 72 weekly for six administrations plus oral etoposide at a dose of 50 mg daily. Of these 98 patients, 38 had a platinum treatment-free interval of more than 12 months, 32 had an interval between 4 and 12 months, and 28 had progressed during or within 4 months after last platinum therapy. We assessed response rates and time to progression, and also response duration and survival. Analyses were done on the 98 evaluable patients. All 107 patients were considered evaluable for toxicity. Of the 38 patients with a treatment-free interval of more than 12 months, 92% responded, with 63% complete responses. The median progression-free survival in these patients was 14 months, and the median survival was 26 months. Of the 32 patients with an interval of 4 -12 months, 91% responded, with 31% complete responses, a median progression-free interval of 8 and a median overall survival of 16 months. Of the 28 patients with platinum-refractory disease, 46% as yet responded, with 29% complete responses, median progression-free interval of 5 and an overall survival of 13 months. Haematologic and non-haematologic, particularly renal toxicity and neurotoxicity, were notably mild. We conclude that this intensive regimen of weekly cisplatin plus daily etoposide is highly effective and well tolerated in patients with ovarian cancer relapsing after conventional platinum-based combination chemotherapy, including patients who have progressed during or within 4 months after platinum treatment.

Weekly platinum chemotherapy for recurrent ovarian cancer

“…However, only 43% of patients with a platinum-free interval of more than 6 months responded. The median survival was 6.3 and 6.9 months respectively in these groups and the toxicity was similar to that reported by Van der Burg et al (2002).…”

“…The article presented by Van der Burg et al (2002) in this issue, may come to challenge this view. The authors report impressive response rates and progression free survival in platinum-sensitive, resistant and refractory disease when treated with weekly cisplatin and prolonged daily oral etoposide.…”

“…For instance, the combination of mitoxantrone and paclitaxel has been recently reported to have a response rate of 69% in a predominantly platinum-refractory population of 33 patients. Grade III/ IV neutropenia was however seen in 64% of cycles (compared with 16% of cisplatin doses as reported by Van der Burg et al (2002)) and G-CSF support was required in 49% (Janat et al, 2000).…”

“…Whilst both Van der Burg et al (2002) and Meyer et al (2001) report impressive response rates in platinum resistant disease with weekly cisplatin and prolonged oral etoposide, how do we explain the large discrepancies in overall survival and response rates in platinum-sensitive patients in these studies? As well as the definitions of platinum-sensitive disease being different (platinum-free intervals of 12 and 6 months respectively), in the study by Meyer et al (2001) platinum-sensitive patients had received more prior chemotherapy (2.63 courses compared to 1.13) and had a shorter platinum free interval (10.5 months vs 25 months).…”

A phase II study of sequential carboplatin, paclitaxel and topotecan in patients with previously untreated advanced ovarian cancer

“…In the present study, 21 patients from the initial response group relapsed and went on to receive second-line chemotherapy (17 patients received single-agent carboplatin, two received carboplatin and paclitaxel, one received weekly cisplatin and etoposide (van der Burg et al, 2002) and one received altretamine). Seven of 14 evaluable patients responded to second-line platinum-containing chemotherapy according to CA125 criteria.…”