Ovarian Epithelial Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Stage III and Stage IV Ovarian Epithelial Cancer Treatment
Several ongoing trials include an intermittent dosing arm comparing both intraperitoneal chemotherapy and conventional-schedule intravenous (IV) treatment in patients after both optimal and suboptimal cytoreduction. When these results are available, it will be easier to identify the patient populations that are best suited for intermittent dosing.
First-line treatment of ovarian cancer is cisplatin, given IV, or its second-generation analog, carboplatin, given either alone or in combination with other drugs. Clinical response rates from these drugs regularly exceed 60%, and median time-to-recurrence usually exceeds 1 year in this subset of suboptimally debulked women. Trials by various cooperative groups in the subsequent 2 decades addressed issues of optimal dose-intensity [12,13,14] for both cisplatin and carboplatin, schedule, and the equivalent results obtained with either of these platinum drugs, usually in combination with cyclophosphamide. With the introduction of the taxane paclitaxel, two trials confirmed the superiority of cisplatin combined with paclitaxel to the previous standard of cisplatin plus cyclophosphamide; however, two trials that compared the agent with either cisplatin or carboplatin as a single agent failed to confirm such superiority in all outcome parameters (i.e., response, time-to-progression, and survival) (see Table 2).
Nevertheless, for patients with ovarian cancer, the combination of cisplatin or carboplatin and paclitaxel has been used as the initial treatment (defined as induction chemotherapy) for several reasons:
- GOG-132 was regarded by many as showing that sequential treatment with cisplatin and paclitaxel was equivalent to the combination because many patients crossed over before progression; moreover, the cisplatin only arm was more toxic because it utilized a 100 mg/m2 dose.
- The Medical Research Council (MRC-ICON3) study, while having fewer early crossovers, could be interpreted similarly in regard to the impact on survival of sequential treatment.
- Data from MRC-ICON4 have shown a survival advantage for patients treated with the combination treatment regimen versus those treated with single-agent carboplatin upon recurrence (see Table 3).
- In past trials, single-agent platinums were not superior to platinum combined with an alkylating agent; therefore, the explanation of a detrimental effect of cyclophosphamide is unlikely.