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Perspectives and challenges in developing small molecules targeting purine nucleoside phosphorylase.European Journal of Medicinal Chemistry May 2024As a cytosolic enzyme involved in the purine salvage pathway metabolism, purine nucleoside phosphorylase (PNP) plays an important role in a variety of cellular functions... (Review)
Review
As a cytosolic enzyme involved in the purine salvage pathway metabolism, purine nucleoside phosphorylase (PNP) plays an important role in a variety of cellular functions but also in immune system, including cell growth, apoptosis and cancer development and progression. Based on its T-cell targeting profile, PNP is a potential target for the treatment of some malignant T-cell proliferative cancers including lymphoma and leukemia, and some specific immunological diseases. Numerous small-molecule PNP inhibitors have been developed so far. However, only Peldesine, Forodesine and Ulodesine have entered clinical trials and exhibited some potential for the treatment of T-cell leukemia and gout. The most recent direction in PNP inhibitor development has been focused on PNP small-molecule inhibitors with better potency, selectivity, and pharmacokinetic property. In this perspective, considering the structure, biological functions, and disease relevance of PNP, we highlight the recent research progress in PNP small-molecule inhibitor development and discuss prospective strategies for designing additional PNP therapeutic agents.
Topics: Purine-Nucleoside Phosphorylase; Humans; Enzyme Inhibitors; Small Molecule Libraries; Molecular Structure; Animals; Antineoplastic Agents; Structure-Activity Relationship; Drug Development
PubMed: 38701712
DOI: 10.1016/j.ejmech.2024.116437 -
European Journal of Medicinal Chemistry Feb 2023The present work describes a quinazolinone-based lead optimization for the development of novel purine nucleoside phosphorylase (PNP) inhibitors with quinazolinone...
Computational, in vitro and radiation-based in vivo studies on acetamide quinazolinone derivatives as new proposed purine nucleoside phosphorylase inhibitors for breast cancer.
The present work describes a quinazolinone-based lead optimization for the development of novel purine nucleoside phosphorylase (PNP) inhibitors with quinazolinone scaffold. Nineteen compounds were proposed and docked against PNP, the best 14 compounds with highest docking and affinity scores and low RMSD values were synthesized. Synthesis of new quinazolinone derivatives with variable acetamide substituents on two positions on quinazoline ring was performed. The structures assigned to the products were concordant with the microanalytical and spectral data. In vitro cytotoxicity on human breast cancer cell line (MCF7) was performed and identified compound 6g as the most potent with IC (0.99 ± 0.11 μM) which was further tested against five different breast cancer cell lines in addition to normal breast cell to determine the selectivity. Compound 6g was subjected to molecular dynamic simulation study, radiolabelling and biodistribution study to investigate its stability and selectivity toward breast cancers. The in vitro PNP inhibition results were aligned with the in silico, cytotoxicity, and biodistribution results where 6g showed the most potent PNP inhibitory activity with IC (0.159 ± 0.007 μM) when compared to Peldesine (BCX-34) IC (0.041 ± 0.002 μM).
Topics: Humans; Female; Purine-Nucleoside Phosphorylase; Breast Neoplasms; Quinazolinones; Tissue Distribution; Enzyme Inhibitors; Acetamides; Structure-Activity Relationship
PubMed: 36610250
DOI: 10.1016/j.ejmech.2023.115087 -
JAAD International Jun 2021Mycosis fungoides (MF) is a cutaneous lymphoma; most patients present with early, skin-limited disease and are managed by dermatologists. (Review)
Review
BACKGROUND
Mycosis fungoides (MF) is a cutaneous lymphoma; most patients present with early, skin-limited disease and are managed by dermatologists.
OBJECTIVE
The purpose of this study was to systematically review and assess the evidence on topical treatments for early-stage (IA, IB, IIA) MF.
METHODS
We performed a literature search via MEDLINE, Embase, Web of Science, and Cochrane databases. Grading Recommendations Assessment, Development and Evaluation (GRADE) criteria were used to assess the certainty of the data.
RESULTS
Two searches yielded 1252 references; 26 met the inclusion criteria and included literature on nitrogen mustard, retinoids, corticosteroids, carmustine, fluorouracil, methotrexate-laurocapram, hexadecylphosphocholine, peldesine, ingenol mebutate, topical methotrexate with oxygen flow-assisted LP3 carrier, and resiquimod. Most studies were single intervention, observational series. Nitrogen mustard, with the most published reports, was effective with 12%-82% early-stage MF patients (total n > 1000) achieving complete remission (CR) (low certainty evidence). Clinical CR was achieved among 10%-60% treated with topical retinoids (low certainty evidence). Two moderate-sized retrospective case series on topical steroids had 18%-63% CR (low certainty evidence). Only single studies were available for the other therapies.
CONCLUSIONS
For most outcomes of interest, the GRADE certainty for topical therapies for early-stage MF was low. Further randomized controlled trials and inclusion of quality of life indicators are needed.
PubMed: 34409369
DOI: 10.1016/j.jdin.2021.01.002 -
The Cochrane Database of Systematic... Jul 2020Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available, which may induce clinical remission for a time. This is an update of a Cochrane Review first published in 2012: we wanted to assess new trials, some of which investigated new interventions.
OBJECTIVES
To assess the effects of interventions for MF in all stages of the disease.
SEARCH METHODS
We updated our searches of the following databases to May 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched 2 trials registries for additional references. For adverse event outcomes, we undertook separate searches in MEDLINE in April, July and November 2017.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of local or systemic interventions for MF in adults with any stage of the disease compared with either another local or systemic intervention or with placebo.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. The primary outcomes were improvement in health-related quality of life as defined by participants, and common adverse effects of the treatments. Key secondary outcomes were complete response (CR), defined as complete disappearance of all clinical evidence of disease, and objective response rate (ORR), defined as proportion of patients with a partial or complete response. We used GRADE to assess the certainty of evidence and considered comparisons of psoralen plus ultraviolet A (PUVA) light treatment as most important because this is first-line treatment for MF in most guidelines.
MAIN RESULTS
This review includes 20 RCTs (1369 participants) covering a wide range of interventions. The following were assessed as either treatments or comparators: imiquimod, peldesine, hypericin, mechlorethamine, nitrogen mustard and intralesional injections of interferon-α (IFN-α) (topical applications); PUVA, extracorporeal photopheresis (ECP: photochemotherapy), and visible light (light applications); acitretin, bexarotene, lenalidomide, methotrexate and vorinostat (oral agents); brentuximab vedotin; denileukin diftitox; mogamulizumab; chemotherapy with cyclophosphamide, doxorubicin, etoposide, and vincristine; a combination of chemotherapy with electron beam radiation; subcutaneous injection of IFN-α; and intramuscular injections of active transfer factor (parenteral systemics). Thirteen trials used an active comparator, five were placebo-controlled, and two compared an active operator to observation only. In 14 trials, participants had MF in clinical stages IA to IIB. All participants were treated in secondary and tertiary care settings, mainly in Europe, North America or Australia. Trials recruited both men and women, with more male participants overall. Trial duration varied from four weeks to 12 months, with one longer-term study lasting more than six years. We judged 16 trials as at high risk of bias in at least one domain, most commonly performance bias (blinding of participants and investigators), attrition bias and reporting bias. None of our key comparisons measured quality of life, and the two studies that did presented no usable data. Eighteen studies reported common adverse effects of the treatments. Adverse effects ranged from mild symptoms to lethal complications depending upon the treatment type. More aggressive treatments like systemic chemotherapy generally resulted in more severe adverse effects. In the included studies, CR rates ranged from 0% to 83% (median 31%), and ORR ranged from 0% to 88% (median 47%). Five trials assessed PUVA treatment, alone or combined, summarised below. There may be little to no difference between intralesional IFN-α and PUVA compared with PUVA alone for 24 to 52 weeks in CR (risk ratio (RR) 1.07, 95% confidence interval (CI) 0.87 to 1.31; 2 trials; 122 participants; low-certainty evidence). Common adverse events and ORR were not measured. One small cross-over trial found once-monthly ECP for six months may be less effective than twice-weekly PUVA for three months, reporting CR in two of eight participants and ORR in six of eight participants after PUVA, compared with no CR or ORR after ECP (very low-certainty evidence). Some participants reported mild nausea after PUVA but no numerical data were given. One participant in the ECP group withdrew due to hypotension. However, we are unsure of the results due to very low-certainty evidence. One trial comparing bexarotene plus PUVA versus PUVA alone for up to 16 weeks reported one case of photosensitivity in the bexarotene plus PUVA group compared to none in the PUVA-alone group (87 participants; low-certainty evidence). There may be little to no difference between bexarotene plus PUVA and PUVA alone in CR (RR 1.41, 95% CI 0.71 to 2.80) and ORR (RR 0.94, 95% CI 0.61 to 1.44) (93 participants; low-certainty evidence). One trial comparing subcutaneous IFN-α injections combined with either acitretin or PUVA for up to 48 weeks or until CR indicated there may be little to no difference in the common IFN-α adverse effect of flu-like symptoms (RR 1.32, 95% CI 0.92 to 1.88; 82 participants). There may be lower CR with IFN-α and acitretin compared with IFN-α and PUVA (RR 0.54, 95% CI 0.35 to 0.84; 82 participants) (both outcomes: low-certainty evidence). This trial did not measure ORR. One trial comparing PUVA maintenance treatment to no maintenance treatment, in participants who had already had CR, did report common adverse effects. However, the distribution was not evaluable. CR and OR were not assessable. The range of treatment options meant that rare adverse effects consequently occurred in a variety of organs.
AUTHORS' CONCLUSIONS
There is a lack of high-certainty evidence to support decision making in the treatment of MF. Because of substantial heterogeneity in design, missing data, small sample sizes, and low methodological quality, the comparative safety and efficacy of these interventions cannot be reliably established on the basis of the included RCTs. PUVA is commonly recommended as first-line treatment for MF, and we did not find evidence to challenge this recommendation. There was an absence of evidence to support the use of intralesional IFN-α or bexarotene in people receiving PUVA and an absence of evidence to support the use of acitretin or ECP for treating MF. Future trials should compare the safety and efficacy of treatments to PUVA, as the current standard of care, and should measure quality of life and common adverse effects.
Topics: Acitretin; Antineoplastic Agents; Bexarotene; Combined Modality Therapy; Humans; Immunologic Factors; Interferon-alpha; Mycosis Fungoides; Neoplasm Staging; PUVA Therapy; Photochemotherapy; Photopheresis; Randomized Controlled Trials as Topic; Skin Neoplasms
PubMed: 32632956
DOI: 10.1002/14651858.CD008946.pub3 -
The British Journal of Dermatology May 2014The authors performed a systematic review of randomized controlled trials (RCTs) on interventions for any stage of typical mycosis fungoides (MF). They searched...
BACKGROUND
The authors performed a systematic review of randomized controlled trials (RCTs) on interventions for any stage of typical mycosis fungoides (MF). They searched electronic databases including the Cochrane Central Register of Controlled Trials, Medline, Embase, and the Latin American and Caribbean Health Science Information database, and included reports from conference proceedings and unpublished data without language restrictions. The authors also searched trial registries affiliated with the U.S.A., Australia, the World Health Organization and the European Organisation of Research and Treatment of Cancer for studies on 'mycosis fungoides' or 'cutaneous T-cell lymphoma'. These searches were supplemented by correspondence with the groups or individuals who conducted the RCTs.
METHODS
The authors included RCTs with participants who were 18 years of age or older, that had staging information, and in which > 90% of patients had biopsy-proven typical CD4+ MF. Data on treatment and outcome of participants, including information on stage of MF, therapy, quality of life, remission or improvement, duration of remission, survival, adverse effects and toxicity were obtained from included studies. Primary outcomes were adverse effects and quality of life. Secondary outcomes were clearance of at least 90% of surface area involvement, improvement of at least 50% of surface area involvement, survival rate, relapse rate and disease-free interval. The authors also recorded potentially significant participant-related prognostic factors, such as age and sex, and tumour-related prognostic factors, such as histological subtype and systemic involvement.
FINDINGS
From 407 unique references, 14 RCTs were included with a total of 675 patients. These trials included skin-directed therapies [topical peldesine, topical imiquimod, topical hypericin, intralesional interferon (IFN)-α, psoralen ultraviolet A (PUVA) therapy, electron-beam therapy (EBT) and local radiation], systemic therapies [extracorporeal photopheresis (ECP), denileukin diftitox, bexarotene] and combination therapies (injected transfer factor with concomitant topical nitrogen mustard use). Only one meta-analysis of two studies comparing PUVA with IFN-α vs. PUVA alone could be performed, and no significant differences between the two therapies were found. Two studies on intralesional IFN-α vs. placebo were included in the review and provided opposing results, but were not examined by meta-analysis due to differences in their study design. The remainder of the Cochrane analysis reviewed outcomes of individual RCTs. There were statistically significant differences in improvement or clearance for five therapeutic regimens. One trial of topical hypericin vs. placebo found a relative benefit of hypericin, risk ratio (RR) for improvement 7·00, 95% confidence interval (CI) 1·01-48·54, P ≤ 0·028. A trial comparing ECP with PUVA demonstrated significantly better improvement in the PUVA group (RR 0·07, 95% CI 0·00-1·00, P ≤ 0·002). An RCT examining 'conservative', stepwise escalation from topical nitrogen mustard to 'combination therapy' with EBT and cyclophosphamide, doxorubicin, etoposide and vincristine chemotherapy found that combination therapy was superior in clearance (RR 2·18, 95% CI 1·10-4·33, P ≤ 0·03) and improvement (RR 1·40, 95% CI 1·12-1·74, P ≤ 0·003). However, there were no statistically significant differences in survival rates at a median follow-up of 75 months. A comparison of subcutaneously injected IFN-α and acitretin vs. subcutaneously injected IFN-α and PUVA found increased clearance with IFN-α and PUVA (RR 0·54, 95% CI 0·35-0·84, P ≤ 0·005). There were also significant reductions in grade III, severe adverse events on the World Health Organization scale; events requiring discontinuation; and neurological disorders in the IFN-α plus PUVA group. Finally, a trial comparing active vs. inactivated transfer factor found significant differences between the groups, favouring inactivated transfer factor (Fisher's exact test, P ≤ 0·03, RR 0·09, 95% CI 0-0·61). The original study authors speculated that their results reflected a better initial prognosis for the group receiving inactivated transfer factor. None of the interventions assessed showed significant long-term benefit. Despite significantly superior clearance rates in four trials, participants in those studies had high relapse rates.
INTERPRETATION
This review of RCTs for MF interventions led to more questions than answers due to a dearth of adequately powered RCTs. Only one meta-analysis could be performed. The remaining review was based on single trials, many of which assessed infrequently used treatments or regimens and are not reflective of current clinical practices. Only two of the 14 RCTs assessed patient health-related quality-of-life outcomes.
Topics: Humans; Mycosis Fungoides; Skin Neoplasms
PubMed: 24841586
DOI: 10.1111/bjd.12954 -
The Cochrane Database of Systematic... Sep 2012Mycosis fungoides is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available, which... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mycosis fungoides is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available, which may induce clinical remission for a time.
OBJECTIVES
To assess the effects of interventions for mycosis fungoides in all stages of the disease.
SEARCH METHODS
We searched the following databases up to January 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2010), and LILACS (from 1982). We also checked reference lists of included studies for further references to relevant RCTs. We searched online trials registries for further references to unpublished trials and undertook a separate search for adverse effects of interventions for mycosis fungoides in non-RCTs in MEDLINE in May 2011.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of interventions for mycosis fungoides in people with any stage of the disease. At least 90% of participants in the trials must have been diagnosed with mycosis fungoides (Alibert-Bazin-type).
DATA COLLECTION AND ANALYSIS
Two authors independently assessed eligibility and methodological quality for each study and carried out data extraction. We resolved any disagreement by discussion. Primary outcomes were the impact on quality of life and the safety of interventions. When available, we reported on our secondary outcomes, which were the improvement or clearance of skin lesions, disease-free intervals, survival rates, relapse rates, and rare adverse effects. When possible, we combined homogeneous studies for meta-analysis. We used The Cochrane Collaboration's 'Risk of bias' tool to assess the internal validity of all included studies in six different domains.
MAIN RESULTS
The review included 14 RCTs involving 675 participants, covering a wide range of interventions. Eleven of the included trials assessed participants in clinical stages IA to IIB only (please see Table 1 for definitions of these stages).Internal validity was considerably low in studies with a high or unclear risk of bias. The main reasons for this were low methodological quality or missing data, even after we contacted the study authors, and a mean dropout rate of 26% (0% to 72%). Study size was generally small with a minimum of 4 and a maximum of 103 participants. Only one study provided a long enough follow-up for reliable survival analysis.Included studies assessed topical treatments, such as imiquimod, peldesine, hypericin, nitrogen mustard, as well as intralesional injections of interferon-α (IFN-α). The light therapies investigated included psoralen plus ultraviolet A light (PUVA), extracorporeal photopheresis (photochemotherapy), and visible light. Oral treatments included acitretin, bexarotene, and methotrexate. Treatment with parenteral systemic agents consisted of denileukin diftitox; a combination of chemotherapy and electron beam radiation; and intramuscular injections of active transfer factor. Nine studies evaluated therapies by using an active comparator; five were placebo-controlled RCTs.Twelve studies reported on common adverse effects, while only two assessed quality of life. None of these studies compared the health-related quality of life of participants undergoing different treatments. Most of the reported adverse effects were attributed to the interventions. Systemic treatments, and here in particular a combined therapeutic regimen of chemotherapy and electron beam, bexarotene, or denileukin diftitox, showed more adverse effects than topical or skin-directed treatments.In the included studies, clearance rates ranged from 0% to 83%, and improvement ranged from 0% to 88%. The meta-analysis combining the results of 2 trials comparing the effect of IFN-α and PUVA versus PUVA alone showed no significant difference in the relative risk of clearance: 1.07 (95% confidence interval 0.87 to 1.31). None of the included studies demonstrated a significant increase in disease-free intervals, relapse, or overall survival.
AUTHORS' CONCLUSIONS
This review identified trial evidence for a range of different topical and systemic interventions for mycosis fungoides. Because of substantial heterogeneity in design, small sample sizes, and low methodological quality, the comparative safety and efficacy of these interventions cannot be established on the basis of the included RCTs. Taking into account the possible serious adverse effects and the limited availability of efficacy data, topical and skin-directed treatments are recommended first, especially in the early stages of disease. More aggressive therapeutic regimens may show improvement or clearance of lesions, but they also result in more adverse effects; therefore, they are to be considered with caution. Larger studies with comparable, clearly-defined end points for all stages of mycosis fungoides, and a focus on safety, quality of life, and duration of remission as part of the outcome measures, are necessary.
Topics: Antineoplastic Agents; Humans; Mycosis Fungoides; Neoplasm Staging; Photochemotherapy; Photopheresis; Randomized Controlled Trials as Topic; Skin Neoplasms
PubMed: 22972128
DOI: 10.1002/14651858.CD008946.pub2 -
Human Research Report May 2006
Topics: Clinical Trials as Topic; Consent Forms; Ethics Committees, Research; Female; Guanine; Guideline Adherence; Humans; Mandatory Reporting; Neoplasms; Research Design; Research Personnel; Research Subjects; United States; United States Office of Research Integrity; Universities
PubMed: 16832916
DOI: No ID Found -
Chemical Research in Toxicology Dec 2003Sodium arsenite is much more potent than sodium arsenate in producing adverse effects in animals and in cultured cells. Although arsenate may exhibit toxicity as a... (Comparative Study)
Comparative Study
Sodium arsenite is much more potent than sodium arsenate in producing adverse effects in animals and in cultured cells. Although arsenate may exhibit toxicity as a phosphate analogue, its potency in vivo appears to be enhanced by reduction to arsenite. To understand the relative importance of this reduction, which is critical in evaluating the responsiveness of cell culture models to the different oxidation states and thus to elucidating the mechanism of arsenic action, present work has correlated the extent of reduction with biological activity in human keratinocytes. The results show that at biologically relevant concentrations, arsenate reduction to appreciable levels required several days, helping rationalize a previous empirical observation that it was approximately one-third as potent as arsenite. The relatively low conversion rate also emphasizes a limitation of culture; arsenate was nearly as efficacious as arsenite, but the time required for it to reach maximal effect exceeded ordinary medium change intervals. In keratinocytes, an important role for purine nucleoside phosphorylase in the reduction could not be demonstrated, indicating that another pathway is dominant in this cell type. Methylation of inorganic arsenic, uptake of methylated forms, and their reduction were all very slow. These findings suggest that the reduced methylated forms have only a small contribution to skin carcinogenesis unless they are supplied through the circulation. In parallel experiments, trivalent antimony was similar to arsenite in potency and efficacy, whereas pentavalent antimony was virtually without biological effect. Conversion of antimony in the pentavalent to the trivalent oxidation state was not detectable in keratinocytes. These findings emphasize the importance of intracellular reduction of the metalloids for biological effects.
Topics: Animals; Antimony; Arsenic; Biotransformation; Cattle; Cell Line; Dose-Response Relationship, Drug; Enzyme Induction; Enzyme Inhibitors; Fibroblasts; Guanine; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Humans; Keratinocytes; Membrane Proteins; Oxidation-Reduction; Protein Precursors; Purine Nucleosides; Purine-Nucleoside Phosphorylase; Pyrimidinones; Pyrroles; Spleen
PubMed: 14680377
DOI: 10.1021/tx034146y -
Clinical Lymphoma Nov 2000Cutaneous T-cell lymphoma (CTCL) includes a heterogeneous group of diseases manifested in many cases by a prolonged clinical course. Even patients with advanced clinical... (Review)
Review
Cutaneous T-cell lymphoma (CTCL) includes a heterogeneous group of diseases manifested in many cases by a prolonged clinical course. Even patients with advanced clinical disease, including erythroderma, adenopathy, and cutaneous tumors, can respond to a number of conservative therapeutic modalities, including radiation, cutaneous and extracorporeal phototherapy, and interferon. More aggressive systemic therapies are generally reserved for patients with visceral involvement or effaced (LN4) lymph node disease or patients refractory to multiple conservative approaches. Since no survival benefit has been demonstrated for multiagent cytotoxic chemotherapy regimens, this therapy is generally reserved for patients whose disease demonstrates an aggressive clinical course requiring immediate palliation. Durable responses (5+ years) have been reported with purine analogues; however, prolonged immunosuppression and increased frequency of opportunistic infections have been demonstrated. Novel therapeutic agents, including interleukin-2, interleukin-12, the phosphorylase inhibitor peldesine (BCX-34), and bexarotene, have demonstrated activity. The interleukin-2 diphtheria toxin fusion protein, DAB(389)IL-2, has demonstrated a 30% response rate in advanced and refractory CTCL patients. The optimal role of targeted biological therapies in advanced patients will likely be in the minimal disease setting following either chemotherapy or radiation.
Topics: Humans; Lymphoma, T-Cell, Cutaneous; Medical Oncology; Skin Neoplasms
PubMed: 11707857
DOI: 10.3816/clm.2000.s.002 -
Journal of the American Academy of... Jun 2001The purine nucleoside phosphorylase inhibitor peldesine is a new agent being evaluated as a T-cell inhibitor. (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
The purine nucleoside phosphorylase inhibitor peldesine is a new agent being evaluated as a T-cell inhibitor.
OBJECTIVE
We attempted to determine the efficacy of peldesine (BCX-34) in a 1% dermal cream formulation as a treatment for cutaneous T-cell lymphoma (CTCL).
METHODS
Ninety patients with patch and plaque phase CTCL, histologically confirmed by a referee dermatopathologist, were enrolled in a randomized, double-blind, placebo-controlled study. BCX-34 dermal cream 1% or the vehicle cream (as a placebo control) was applied twice daily to the entire skin surface for up to 24 weeks. Efficacy of the topical therapy was assessed in terms of complete or partial (> or = 50%) clearing of patches and plaques.
RESULTS
Of the 89 patients able to be examined, 43 received BCX-34 and 46 received the placebo vehicle cream. One patient withdrew early and was not analyzed. The two groups were well balanced for potential prognostic factors. A total of 28% (12/43) of the patients treated with BCX-34 showed a response, but 24% (11/46) of patients who received vehicle also responded (P =.677).
CONCLUSION
Although BCX-34 dermal cream 1% was not significantly better than the control as therapy for patch and plaque-phase CTCL, this appears to be the first published placebo-controlled trial evaluating treatment for CTCL. Whether the vehicle cream has more than a placebo therapeutic effect is unclear. The relatively high (24%) placebo response rate should be kept in mind in assessing other treatments for early-stage CTCL.
Topics: Administration, Cutaneous; Adult; Aged; Double-Blind Method; Enzyme Inhibitors; Female; Guanine; Humans; Lymphoma, T-Cell, Cutaneous; Male; Middle Aged; Placebos; Treatment Outcome
PubMed: 11369904
DOI: 10.1067/mjd.2001.113478