Prevention of nausea and vomiting (N&V) in cancer patients receiving high-dose cisplatin. Assessment of the potential antiemetic activity of transdermal fentanyl (TTS-F) compared to standard antiemetic treatment in acute and delayed N&V: first clinical report

A single-institution, prospective, open crossover study was performed to compare the effectiveness and tolerability of transdermal fentanyl (TTS-F) vs intravenous (i.v.) ondansetron (OND), both combined with i.v. DEX, in the prevention of acute nausea and vomiting (N and V), and TTS-F vs metoclopramide (M), both combined with intramuscular (i.m.) DEX, in the prevention of delayed N and V in patients with advanced stage head and neck squamous cell carcinoma receiving high-dose (≥ 100 mg/m2) cisplatin. This is the first report on the clinical use of TTS-F in this setting. Patients and methods. All patients were adequately informed of the study characteristics and gave their written informed consent before study entry. The antiemetic treatment for acute N and V consisted of A) OND 8 mg plus DEX 20 mg (i.v.) or B) TTS-F 75 μg/h plus DEX 20 mg i.v. For prevention of delayed N and V, patients receiving TTS-F for acute N and V were given TTS-F at the same dosage (75 μg/h) on days 2-5, whereas patients receiving OND for acute N and V were treated with M 20 mg orally every 6 h on days 2-5, starting 24 h after CDDP. All patients received DEX 8 mg i.m. every 12 h on days 2 and 3, 4 mg i.m. every 12 h on days 4 and 5, starting 24 h after CDDP. From November 1997 to April 1998, 15 consecutive patients entered the study and were assigned to one of the two alternative treatments for acute N and V. All of them were evaluable. Twelve patients were evaluable for delayed N and V. Seven patients were assigned to Group 1 starting with treatment A (OND + DEX) and 8 patients were assigned to Group 2 starting with treatment B (TTS-F + DEX). In the prevention of acute N and V, the overall efficacy of OND + DEX was statistically significantly higher than that of TTS-F + DEX in achieving Complete Response (CR) and Major Efficacy (ME = CR + Major Response, MaR). As for delayed N and V, the overall efficacy of M + DEX, both in achieving CR and ME, although higher, was statistically not significantly different from that of TTS-F + DEX. Unfortunately, due to the small number of patients included in the study, the sophisticated criteria for evaluating response in antiemetic research, such as the persistence of efficacy, the response after crossing-over, did not make it possible for us to draw additional conclusions, although the trend was in favor of 'standard' treatments, particularly in acute N and V. The response to treatment A (OND + DEX) in the prevention of acute N and V was in the same range as the response to treatment A (M + DEX) for delayed N and V. The response to treatment B (TTS-F) for acute N and V was lower than the response to the same treatment for delayed N and V. The TTS-F treatment was well-tolerated with no significant side-effects including the well-known opioid-related symptoms. Our study confirms that the currently available standard antiemetic treatments both for acute and delayed N and V must be considered by far the most effective ones for clinical use.