There were slightly more deaths in patients treated with OROS® hydromorphone compared with morphine in the previous equivalence study; however, all deaths were considered unrelated or unlikely

to be related to study treatment. The occurrence of these deaths was not unexpected given the severity of patients’ conditions and the progressive nature of the disease. Of the 32 patients who reported other SAEs, the majority of the events were considered unrelated Inhibitors,research,lifescience,medical or unlikely to be related to study treatment. 8 patients had SAEs that were considered to have a possible, probable, or definite relationship to study treatment. 9 patients reported AEs that led to early discontinuation from the study, and most of these AEs were considered probably related to study treatment. In conclusion, OROS® hydromorphone was found to be safe and reasonably well tolerated in this extension study. There are a number of limitations of this study, which may affect the interpretation of the results. Inhibitors,research,lifescience,medical This was an open-label, uncontrolled study, so the results cannot be directly compared to either no therapy or other opioid therapies. A large number of patients (58/68; 85.3%) did not complete the study. However, this is not unexpected given the severity and progressive nature

of the disease; in fact, a large number of patients did Inhibitors,research,lifescience,medical not complete the study owing to death (n = 15) and progression of disease (n = 14). Dropouts due to lack of efficacy were uncommon (n = 8), but were to be expected given the progression Inhibitors,research,lifescience,medical of cancer.

A further limitation was that no formal statistical analyses were done on the data. This was an open-label, single treatment arm trial mainly assessing the safety of long-term usage and secondary maintenance of efficacy; therefore, all analyses were done descriptively. End point was calculated using the LOCF method, a method that LEE011 in vivo involves extrapolating the last observed measurement for the patient. This method Inhibitors,research,lifescience,medical was necessary because the study involved multiple visits and a critically ill patient population, and therefore a high number of dropouts was expected. Perifosine In spite of these limitations, this study has provided useful insights into the effectiveness of the long-term use of OROS® hydromorphone for relief of cancer pain, which may be applicable to clinical practice. It also suggests that conversion from previous opioid therapy to OROS® hydromorphone is feasible without loss of pain control. The effective morphine to hydromorphone conversion ratio varies from 4:1 to 8:1 in different publications [9,33,49-53]. A 5:1 morphine equivalents to hydromorphone conversion ratio is most often cited in the literature [21,22,34,43-46] and was found to be clinically useful in this study. The study population represents a rather small selected subgroup of patients, i.e.