Decreased occurrence of osteonecrosis of the jaw after implementation of dental preventive measures in solid tumour patients with bone metastases treated with bisphosphonates. The experience of the National Cancer Institute of Milan.

BACKGROUND: Screening of the oral cavity and dental care was suggested as mandatory preventive measures of osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BPs). We investigated the occurrence of ONJ before and after implementation of dental preventive measures when starting BP therapy. PATIENTS AND METHODS: Since April 2005, 154 consecutive patients treated with BPs (POST-Group) have undergone a baseline mouth assessment (dental visit +/- orthopantomography of the jaws) to detect potential dental conditions and dental care if required. A retrospective review was also conducted of all consecutive cancer patients with bone metastases (PRE-Group) and treated for the first time with BPs from January 1999 to April 2005 in our clinic without receiving any preventive measure. Incidence proportion and incidence rate (IR) were used to estimate the incidence of ONJ. RESULTS: Among the study population (966 patients; male/female=179/787), 73% had breast cancer. 25% of patients were given zoledronic acid (ZOL), 62% pamidronate (PAM), 8% PAM followed by ZOL and 5% clodronate. ONJ was observed in 28 patients (2.9%); we observed a reduction in the incidence of ONJ from 3.2% to 1.3%, when comparing-pre and post-implementation of preventive measures programme. Considering the patients exposed to ZOL, the performance of a dental examination and the application of preventive measures led to a sustained reduction in ONJ IR (7.8% in the PRE-Group versus 1.7% in the POST-Group; P=0.016), with an IR ratio of 0.30 (95% confidence interval 0.03-1.26). CONCLUSIONS: ONJ is a manageable and preventable condition. Our data confirm that the application of preventive measures can significantly reduce the incidence of ONJ in cancer patients receiving BPs therapy. Dental exams combined to the identification of patients at risk in cooperation with the Dental Team can improve outcomes and increase the number of ONJ-free patients.

The MERITO Study: a multicentre trial of the analgesic effect and tolerability of normal-release oral morphine during 'titration phase' in patients with cancer pain.

Adequate and rapid pain control is one of the main goals of cancer pain treatment. The objective of this study was to assess the effect and tolerability of oral normal-release morphine during the initial phase of treatment in patients with moderate-to-severe cancer pain. Consecutive patients naïve to strong opioids received normal-release morphine 5 or 10 mg every 4 h during the titration phase (first 5 days), depending on previous analgesic therapy. Pain intensity was assessed using an 11-point Numerical Rating Scale (0-10), and data were recorded in a patient-compiled diary. The primary endpoint was the proportion of time with pain control (a reduction of at least 50% with respect to the baseline pain score) during the titration phase. A total of 159 consecutive patients (102 men; mean age 65 years) with cancer-related pain were enrolled. Pain control was observed for 75% (95% CI 70-80) of the follow-up period in the intent-to-treat population. Overall, 50% and 75% of patients achieved pain control within 8 and 24 h after starting normal-release morphine therapy respectively. The mean pain score was 7.63 points at baseline, and decreased to 2.43 and 1.67 points (both P<0.001) at days 3 and 5 respectively. The most commonly reported adverse events were somnolence (24% of patients), constipation (22%), vomiting (13%), nausea (10%) and confusion (7%). Normal-release morphine results in rapid and satisfactory pain control, and is well tolerated, during the strong-opioid titration phase in patients with moderate-to-severe cancer pain.