Subcutaneous administration of amifostine: a promising therapeutic option in patients with oxaliplatin-related peripheral sensitive neuropathy.

Subcutaneous administration of amifostine: A promising therapeutic option in patients with oxaliplatin-related peripheral sensitive neuropathy. Oxaliplatin, a third-generation platinum compound with a 1,2-diaminocyclohexane (DACH) carrier ligand, is a recently developed agent with a broad spectrum of antineoplastic activities [1]. Hallmarks of this novel agent include its lack of cross-resistance with cisplatin and carboplatin, synergistic activity with various other cytotoxic agents such as 5-fluorouracil-leucovorin, and an excellent safety profile with a specific and manageable set of toxicities. When given alone or in combination with other cytotoxic drugs at its recommended dose of 85 mg/m 2 every two weeks or 130 mg/m 2 every three weeks, haematological side effects are commonly seen, but are generally mild. The most frequently encountered nonhaematological adverse events include gastrointestinal symptoms and a peripheral neurosensory toxicity (PNP), characterised by pares-thesia and/or dysesthesia triggered or exacerbated by exposure to cold. This side effect, which is cumulative but reversible in most patients a few months after stopping treatment, does represent the principal dose-limiting toxicity in patients receiving oxaliplatin [1]. Amifostine (WR-2721; ethyol) is a thiophosphate cytoprotec-tant agent with the potential to abrogate many chemotherapy-induced toxicities [2], In preclinical studies, amifostine protected against the cytotoxic side effects of alkylating agents, platinum analogues, and radiation therapy in normal tissues, but preserved antineoplastic activity of these therapeutic modalities in tumour tissue. Most normal tissues were protected, including bone marrow, kidney, lung, and peripheral nerves. Usually amifostine is administered as a short intravenous (i.v.) infusion over 15 minutes. Recent pharmacokinetic studies, however, have shown acceptable plasma levels of its active metabolite (WR-1605) after subcutaneous (s.c.) injection [3], and Koukourakis et al. have subsequently established feasibility, efficacy as well as a superior tolerance of this simplified administration schedule in a randomised phase II trial involving 140 patients with head and neck, thoracic, and pelvic cancers undergoing radical radiotherapy [4]. In the present pilot study, we have investigated the therapeutic potential of an identical s.c. administration schedule of the cytoprotective agent amifostine to counteract oxaliplatin-related PNP. Nine patients with metastatic colorectal cancer receiving chemotherapy with raltitrexed 3 mg/m 2 plus oxali-platin 130 mg/m 2 every three weeks and six patients receiving irinotecan 175 mg/m 2 plus oxaliplatin 85 mg/m 2 both given i.v. on days 1 and 14 every four weeks were enrolled onto this study until today. All patients gave written informed consent according to institutional regulations. Their pretreatment characteristics are summarised in Table …