High dose cisplatin compared with high dose cyclophosphamide in the management of advanced epithelial ovarian cancer (FIGO stages III and IV): report from the North Thames Cooperative Group.

Abstract

A randomised study comparing cisplatin 120 mg intravenously with cyclophosphamide 2 g intravenously, each drug being given every month for six months followed by a low dose regimen for a further six months in responding patients, was carried out in 86 patients with advanced epithelial ovarian carcinoma (FIGO stages III and IV).Patients given cisplatin were found to have a longer median survival time than those given cyclophosphamide (19 months compared with 12 months) and a longer median duration of complete clinical response (18 months compared with eight months). The difference in disease free survival was statistically significant even after factors such as age, stage of disease, and the completeness of initial surgery had been taken into account.This study suggests that cisplatin is a more effective chemotherapeutic agent than cyclophosphamide for advanced ovarian cancer and should be the agent of choice in future trials comparing combination chemotherapy with a single agent.

Editorial: Advances in Epithelial Ovarian Cancer Therapy

“…In 1985, the North Thames Cooperative Group reported the results of the first randomized comparison of first-line single-agent cisplatin with the alkylating agent cyclophosphamide in 86 women with advanced ovarian cancer, and showed significantly longer survival and response duration in patients receiving platinum therapy [4]. These and other data including meta-analyses showed that platinum-based chemotherapy is better than nonplatinum therapy [4][5][6][7] and suggested a trend in favor of platinum combinations with an alkylating agent or alkalating agent and anthracycline over single-agent platinum [8][9][10]. However, on the basis of the subsequent ICON-2 and ICON-3 trials, that used broad inclusion criteria, carboplatin monotherapy was considered a good alternative [11,12].…”

“…The ICON-4 trial randomly assigned paclitaxel plus platinum chemotherapy or conventional platinum-based chemotherapy in patients with platinumsensitive ovarian cancer relapsing after 6 months of being treatment-free [28]. Survival curves showed a difference in favors of paclitaxel plus platinum (hazard ratio 0.82 [95% CI 0.69-0.97], p=0.02), corresponding to an absolute difference in 2-year survival of 7% between the paclitaxel and conventional treatment groups (57 vs 50% [95% CI for difference 1-12]), and median survival of 5 months (29 vs 24 months [95% CI for difference [1][2][3][4][5][6][7][8][9][10][11]). …”

Efficacy of platinum chemotherapy agents in the adjuvant setting for adenosquamous carcinoma of the pancreas.

“…Platinum-based agents have demonstrated improved outcomes in squamous cell cancers in other tumor sites such as the esophagus (26,27), head and neck (28)(29)(30)(31), and ovary (32)(33)(34)(35). The addition of cisplatin to gemcitabine as first-line therapy for pancreatic cancer, however, failed to demonstrate improved survival in patients with diverse histological subtypes in two Italian randomized trials (36,37).…”

Primary chemotherapy and maintenance therapy in epithelial ovarian cancer

“…For several decades surgery alone, and later complemented with alkylating agents used as monotherapy, was considered the treatment of choice and permitted complete clinical response in approximately 20% of patients [2]. In the mid-1970s, cisplatin was recognized as a signifi cant drug in the treatment of ovarian cancer and through randomized studies was adopted in the fi rst-line chemotherapy regimens [3]. Since then, a number of issues have arisen: (i) the question of single-agent platinum versus multi-agent chemotherapy (ii) the choice of platinum agent, given the development of other platinum analogues such as carboplatin and oxaliplatin and (iii) the ideal number of cycles to be administered as a standard of care.…”