Total platinum dose versus platinum dose intensification in ovarian cancer treatment

Multiple in vitro and in vivo studies demonstrate the importance of platinum dose intensity in chemotherapy of advanced ovarian cancer. The relevant areas discussed in this report include (1) retrospective analysis of platinum dose intensity and outcome of ovarian cancer therapy, (2) in vitro human tumor cell line drug assay data, (3) fresh human ovarian tumor cloning data, (4) platinum pharmacokinetics with an emphasis on the relationship between the platinum concentration x time product and cytotoxicity, and (5) prospective clinical studies designed to test the importance of platinum dose intensity alone or platinum dose intensity and total dose. When attempting to design optimal platinum-based therapies for ovarian cancer, it is important to bear in mind the following considerations: (1) both platinum dose intensity and total dose should be increased; (2) to achieve exponential cytotoxicity (eg, up to 10-fold increases in tumor cell kill) by increasing the platinum dose, it is critical to select a platinum dose capable of overcoming inherent drug resistance; (3) carboplatin may be the platinum analogue of choice for dose intensification studies since, unlike cisplatin, it is rarely associated with cumulative nonhematologic toxicity (and as a result can be escalated up to five to six times the standard dose); and (4) the Calvert formula should be used for determining carboplatin dose to safely and accurately target desired drug exposure (as measured by the concentration x time product) and degree of hematologic toxicity.