Nausea and vomiting during chemotherapy are an important issue for a large number of patients since these problems may compromise the quality of life, the compliance to chemotherapy schedule and dose intensity. Administration of DMX and 5-HT3 antagonists is the standard therapy for patients treated with HEC. Even though a complete protection against acute emesis after HEC is documented in 70-90 percent of patients unresponsive patients are still a challenge. Midazolam is a short acting benzodiazepine used as a preanesthetic and sedation drug.This study was designed to evaluate the efficacy and tolerability of midazolam in patients treated with HPC unresponsive to standard antiemetic therapy. From January 2001 to April 2002 we enrolled 30 patients who reported, during the first cycle of chemotherapy, WHO G2 nausea and/or vomiting unprotected by DMX and 5-HT3 antagonist. The median age was 54 years (30-68). According to a previous phase I study (Gralla et al.1993) Midazolam 0.04 mg/kg was added to standard antiemetic therapy, as i.v. continuous infusion during chemotherapy in an outpatient setting. Assessment of acute emesis was recorded by each patient on a diary card for days 1 and 2. Patients were interviewed by a physician and a nurse to record nausea and vomiting according to WHO and VAS scales (0-10). A hundred and sixteen cycles were evaluated for efficacy and toxicity.
Results: The median VAS for nausea was 8.93 and 2.37 (matched pairs T-test p<0.0001, CI 95% 4.77-5.96), while that for vomiting was 9.03 and 2.38 before and after midazolam (p<0.0001, CI 95% 5.08-6.59). Seven patients obtained a complete control of anticipatory vomiting The only side effect was mild sedation that resolved within 1 hour.
Conclusion: Our data show that midazolam as continuous infusion during HPC is safe and effective to counteract the acute and anticipatory emetic effect of HPC in patients resistant to standard antiemetic therapy.