Therapeutic efficacy of various dosages and modalities of administration

Cisplatin is one of the most effective agents available for cancer chemotherapy. This drug showed noteworthy activity in several tumor types but, in particular, in genitourinary, gynecologic and head and neck cancer. In each of these tumors, cisplatin has become a focal point for combination chemotherapy studies. In fact the low to moderate hematologic toxicity of conventional doses and the possibility of preventing the renal toxicity by adequate hydration allows cisplatin to combine well with other myelosuppressive agents. Nowadays in testicular cancer, platinum-based combinations are able to cure also disseminated disease, and a high percentage of stage III–IV ovarian cancer patients submitted to debulking surgery and chemotherapy including cisplatin, may have a long survival and possibly a cure. A good palliation is also possible in bladder cancer, head and neck tumors and in advanced osteosarcoma: in these tumors new opportunities for treatment are offered employing cisplatin-containing regimens in neo- adjuvant chemotherapy. Activity for cisplatin has also been reported in cervix or endometrial cancer, prostate and lung cancer, pediatric solid tumors and lymphomas. While waiting for new platinum analogs with more therapeutic activity and less toxicity to be introduced in clinical practice, oncologists are trying to enhance the therapeutic efficacy of the drug by particular 'schedules' of administration. These efforts led to very interesting results: loco- regional infusions, continuous intravenous and intra- cavitary administrations or high dose cisplatin in hypertonic saline have been shown to be able to improve the results of cisplatin conventional doses consisting of 100 mg/mq i.v. every 3 weeks or 20 mg/mq i.v. for 5 consecutive days every 3 weeks. The purpose of all these modalities is to expose the tumor to very high drug concentrations which usually cannot be achieved by intravenous administration. In fact a very steep dose-response correlation was demonstrated for cisplatin-sensitive tumors. Loco- regional infusion has been used preoperatively in head and neck cancer and osteosarcoma in order to shrink tumor masses, Intracavitary cisplatin has major indications in tumors confined to peritoneal cavity, such as ovarian cancer, provided sodium thiosulfate administration is used to avoid systemic toxicity. Finally, high dose cisplatin in hypertonic saline seems to be very promising, but relevant myelotoxicity and neurotoxicity are still related to the treatment.