Is There a Role for Adjuvant High-Dose Interferon-α-2b in the Management of Melanoma?Sabel, Michael; Sondak, Vernon
doi: 10.2165/00003495-200363110-00001pmid: 12749732
The knowledge that melanoma is susceptible to attack by the host’s immune system has resulted in the testing of a variety of immunotherapies. Interferon-α-2b, which has several anti-tumour mechanisms including an antiproliferative effect, an anti-angiogenesis effect, the enhancement of natural-killer cell activity and the upregulation of tumour antigen presentation, has shown tremendous potential. Early trials using low-dose and intermediate-dose regimens demonstrated no benefit to survival. However, the Eastern Cooperative Oncology Group trial EST 1684, showed that a high-dose regimen involving an induction phase of intravenous interferon-α-2b 20 MU/m2 5 days a week for 4 weeks, followed by a maintenance phase of subcutaneous 10 MU/m2 3 days a week for the remainder of a year, led to significant improvements in both disease-free and overall survival compared with observation. On the basis of these results, the US FDA approved high-dose interferon-α-2b for the post-surgical adjuvant therapy of high-risk melanoma. Unfortunately, the results of subsequent trials involving high-dose interferon-α-2b have not been as clear, and its role in the adjuvant treatment of melanoma remains controversial. Concerns remain regarding the design and interpretation of the clinical trials, the cost and toxicity of treatment, and the appropriate selection of patients who should be treated. This article reviews the existing data and attempt to address the arguments for and against a role for adjuvant high-dose interferon-α-2b in the management of melanoma.
Management of Patients with Recurrent Vulvovaginal CandidiasisSobel, Jack
doi: 10.2165/00003495-200363110-00002pmid: 12749733
Recurrent vulvovaginal candidiasis (RVVC) is by no means uncommon and is a source of considerable physical discomfort in addition to serving as a major therapeutic challenge. The syndrome is multifactorial in aetiology and hence management strategies must recognise the complex aetiological pathways. Many women receiving the misplaced diagnosis of RVVC have a variety of other infectious and non-infectious entities presenting with identical symptoms. Hence the first step in management is confirming the diagnosis of RVVC including microbial confirmation and species identification. Efforts should be made to identify and correct a causal mechanism. Maintenance suppressive azole anti-fungal regimens are highly effective in controlling symptoms, although cure is less common. Further advances in achieving higher cure rates await the availabilityof non-azole fungicidal agents.
Darbepoetin AlfaCvetkovic, Risto; Goa, Karen
doi: 10.2165/00003495-200363110-00003pmid: 12749734
▴ Darbepoetin alfa, novel erythropoiesis stimulating protein closely related to human erythropoietin, has been developed for the treatment of chemotherapy-related anaemia in patients with non-myeloid malignancies.
▴ In three 12-week, phase II studies in patients with cancer and chemotherapy-related anaemia, subcutaneous darbepoetin alfa, administered in once-weekly or 2-, 3- or 4-weekly regimens, dose-dependently increased the mean haemoglobin levels.
▴ In a randomised, double-blind, phase III study in 320 patients with lung cancer and chemotherapy-related anaemia, recipients of subcutaneous darbepoetin alfa 2.25 μg/kg once weekly, received red blood cell (RBC) transfusion ≈2-fold less frequently than placebo recipients (p < 0.001).
▴ In the same study, patients receiving darbepoetin alfa also received fewer standard units of RBC for transfusion and had greater haematopoietic response rate than placebo recipients (both p < 0.001).
▴ Subcutaneous darbepoetin alfa 2.25 μg/kg once weekly also reduced patient-reported fatigue (assessed by a quality-of-life questionnaire) [p = 0.019 vs placebo].
▴ Darbepoetin alfa was generally well tolerated in clinical trials. The most frequent darbepoetin alfa-related adverse events were: body oedema, arthralgia and skin rash.
Tramadol/ParacetamolMcClellan, Karen; Scott, Lesley
doi: 10.2165/00003495-200363110-00007pmid: 12749738
▴ The orally administered fixed combination tablet of tramadol (centrally-acting opiate) plus paracetamol (acetaminophen; nonopiate, nonsalicylate analgesic) [37.5/325mg] provides effective analgesia in patients with moderate to severe acute pain and those with chronic painful conditions characterised by intermittent exacerbations of pain.
▴ Two tramadol/paracetamol 37.5/325mg tablets provided greater relief of dental pain over an 8-hour period than either agent alone, with a faster onset of action than tramadol alone and a longer duration of action than either agent as monotherapy.
▴ In patients with postoperative dental pain, two tramadol/paracetamol tablets (37.5/325mg) provided similar analgesia to hydrocodone/paracetamol 10/ 650mg over an 8-hour period.
▴ The addition of one or two tramadol/paracetamol 37.5/325mg tablets (up to four times daily) for 5 days to existing NSAID or cyclo-oxygenase-2 inhibitor analgesic therapy provided effective pain relief in patients with osteoarthritis flare pain.
▴ Tramadol/paracetamol 37.5/325mg provided similar efficacy to that of codeine/paracetamol 30/ 300mg in patients with chronic back pain in a 4-week, randomised, double-blind trial (a maximum of 10 tablets or capsules per day of the active drug).
Lamivudine/Zidovudine/AbacavirIbbotson, Tim; Perry, Caroline
doi: 10.2165/00003495-200363110-00010pmid: 12749741
▴ The triple combination tablet containing lamivudine (150mg), zidovudine (300mg) and abacavir (300mg, as abacavir sulfate) is a new formulation of three nucleoside analogue reverse transcriptase inhibitors.
▴ Two studies in treatment-naive patients (one double-blind, one nonblind) have reported that lamivudine/zidovudine (dual combination tablet) plus abacavir showed efficacy similar to that of lamivudine/zidovudine plus indinavir. In both studies, similar numbers of patients in each treatment group had plasma HIV RNA levels <400 copies/mL at week 48 (51% vs 51% and 64% vs 50%).
▴ In treatment-experienced patients with baseline plasma HIV RNA levels <50 copies/mL, switching to lamivudine/zidovudine/abacavir (triple combination tablet) was as effective as remaining on highly active antiretroviral treatment (mainly protease inhibitor [PI]-based). Virological failure, the primary endpoint, defined as two consecutive plasma HIV RNA values >400 copies/mL, was reported in 22% of patients in both treatment groups at week 48.
▴ Treatment-naive patients receiving lamivudine/zidovudine/abacavir combination therapy experienced several adverse events, including nausea, malaise/fatigue and vomiting.