Weekly scheduling of cisplatin: feasibility, efficacy and perspective

In this thesis studies of weekly administration of cisplatin are presented. Weekly administration of cisplatin is not new: already in the seventies weekly cisplatin regimens were explored but they were abandoned because of hematologic, renal and gastrointestinal toxicity. The administration of cisplatin in the outpatient setting and without adequate hydration certainly has contributed to the failure of these studies. A better understanding of the pathophysiology of renal toxicity led to hydration programs and the introduction of hypertonic saline; the development of a new generation of antiemetics ameliorated nausea and vomiting considerably and made it possible to administer cisplatin more frequently. Reexploration of weekly cisplatin thus became possible. The theory behind weekly administration of cisplatin is based on the tumor biologic principle that frequent administration of chemotherapy in a high dose kills cancer cells more effectively and probably reduces the risk of the development of resistance. Treatment with weekly intervals also has the theoretical advantage that sensitive cells, in which DNA-repair is less effective than in resistant cells, have less time for regrowth compared to conventional 3-week schedules. In this introduction the cytotoxic drugs used in our studies, cisplatin and etoposide, will be briefly discussed as well as the tumor types in which they were studied: head and neck cancer, non-small cell lung cancer and pleural mesothelioma. The indications for chemotherapy in these tumor types as well as the treatment results with cisplatin with or without etoposide will be presented to enable reference with the results presented in this thesis.

• View at Worldcat

Free Full Text ( Final Version , 3mb )