The objective of this open-label, repeated-dose, single-treatment, multicenter study was to evaluate the outcomes associated with a standardized conversion from prior opioid therapy to a novel, once-daily, OROS osmotic technology, extended-release (ER) hydromorphone formulation in an outpatient population with chronic malignant or nonmalignant pain. The study period was divided into 3 phases: the prior opioid stabilization phase (> or =3 days), the conversion and titration phase (3-21 days), and the maintenance phase (14 days). Patients were evaluated at 5 visits during the study period. Analgesic efficacy was measured using the Brief Pain Inventory (BPI). At baseline, patients were required to have daily oral morphine equivalent requirements of > or =45 mg. Prior oral or transdermal opioid therapy was converted to single daily doses of ER hydromorphone (8, 16, 32, and 64 mg tablets) at a 5:1 (morphine equivalent to hydromorphone) ratio. Immediate-release (IR) hydromorphone was given as rescue medication for breakthrough pain. Among the 445 patients who enrolled, 404 received the study medication. Of these, 73 (18.1%) had chronic malignant pain and 331 (81.9%) had chronic nonmalignant pain. Dose stabilization (defined as a 3-day period during which the total daily dose of ER hydromorphone remained unchanged and < or =3 doses of IR hydromorphone per day were required) was attained by 73.8% of patients (298/404), of whom 70.1% (209/298) were stabilized with < or =2 titration steps. The mean +/- standard deviation (SD) time to dose stabilization was 12.1 +/- 5.7 days (range of 3 to 33 days). The mean +/- SD final daily dose of ER hydromorphone was 63.4 +/- 129.2 mg. The mean +/- SD final daily dose of IR hydromorphone was 11.5 +/- 36.4 mg, and the mean +/- SD final number of daily doses of IR hydromorphone was 1.7 +/- 1.3. Intent-to-treat and completer analysis demonstrated significant improvements in BPI ratings from prior opioid therapy to the end of ER hydromorphone therapy (P < 0.01 for all pairwise comparisons). Adverse events were consistent with those expected of an opioid agonist in such a patient group, affecting primarily the gastrointestinal and central nervous systems. This uncontrolled study delineates a regimen by which patients with chronic malignant or nonmalignant pain can be readily converted from prior opioid therapy and titrated to an appropriate maintenance dose of ER hydromorphone. Controlled longitudinal studies are required to further evaluate the use of ER hydromorphone in patients with discrete chronic malignant or nonmalignant pain conditions.

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Extracorporeal photochemotherapy (ECP; photopheresis), an immunomodulatory therapy developed for cutaneous T-cell lymphoma, has shown promise in treating chronic graft-versus-host disease (cGvHD) in uncontrolled studies. The purpose of this study was to further examine the effects of ECP on cGvHD. ECP (administered initially 3 times weekly on alternating days) was retrospectively evaluated in 14 patients with extensive cGvHD following allogeneic hematopoietic stem cell transplantation. The median time from transplantation to ECP initiation was 29 months (range, 5-96 months). The median number of concomitant baseline treatments per patient was 3 (range, 0-5). During a median ECP duration of 17 months (range, 3-44 months), 3 patients (21%) achieved a complete cutaneous response (100% improvement), 4 patients (29%) achieved a partial cutaneous response (> or =50% improvement), and 7 patients (50%) had stable skin disease. The median time to response was 6 months (range, 2-15 months), and the median response duration was 5 months (range, 1-31 months). At endpoint, responses were ongoing in 4 patients. Resolution or improvement was noted in arthralgia (5/7 patients), oral changes (3/7), elevated liver enzymes (3/5), dry eyes (2/5), joint stiffness (3/3), pulmonary disease (1/3), and thrombocytopenia (1/1). Because of a favorable response, 11 of 13 patients (85%) who received prednisone at baseline were able to taper (7/13; 54%) or discontinue (4/13; 31%) this medication, and 12 of 14 patients (86%) were able to taper (11/14; 79%) or discontinue (1/14; 7%) ECP. Five-year posttransplantation survival was 77%. Our results suggest that adjunctive ECP improves cutaneous and extracutaneous manifestations of cGvHD and has a steroid-sparing effect.

Summary:Extracorporeal photochemotherapy (ECP; photopheresis), an immunomodulatory therapy, has previously demonstrated promising results in treating chronic graftversus-host disease (cGvHD). We treated six patients (ages 33-54 years) with long-standing refractory extensive-stage cGvHD. ECP was performed thrice weekly initially in all patients. Concomitant therapies included prednisone (n ¼ 6), tacrolimus (n ¼ 5), cyclosporin A (n ¼ 2), hydroxychloroquine (n ¼ 2), mycophenolate mofetil (n ¼ 1), and psoralen plus ultraviolet A radiation (n ¼ 1). After an average of 7.2 months (range, 2-13 months) of ECP, all patients experienced either improvement or stabilization in sclerodermatous skin changes, as well as partial improvements in liver enzyme levels. Skin softening occurred in four patients and was noted as early as 3-8 weeks into treatment. Two patients were able to taper steroid therapy, and two patients were able to taper ECP to twice weekly. ECP was well tolerated. Our results support those of previous studies, suggesting that ECP may be beneficial in patients with refractory cGvHD.

This study suggests that extended use of extracorporeal photochemotherapy in the management of early-onset, diffuse PSS is well tolerated and may provide an increasingly beneficial clinical outcome.