Bexarotene: a clinical review

Bexarotene (Targretin, Ligand Pharmaceuticals Inc.) is a synthetic retinoid analog with specific affinity for the retinoid X receptor and belongs to a group of compounds called rexinoids. Early clinical trials of this drug demonstrated activity in cutaneous T-cell lymphoma. Subsequent Phase II/III trials have demonstrated a greater than 50% response rate in patients with all stages of cutaneous T-cell lymphoma who were refractory or intolerant to the previous therapy. The principal toxicities of bexarotene include central hypothyroidism, xeroderma and elevation of cholesterol and triglycerides. These toxicities can be managed with dose attenuation or addition of atorvastatin (Lipitor, Pfizer) or fenofibrate (TriCor, Abbott Laboratories). Since bexarotene has little bone marrow toxicity, it is an excellent candidate for combination therapy with other modalities useful in the treatment of cutaneous T-cell lymphoma. These include ultraviolet B irradiation, psoralen and ultraviolet A photochemotherapy, interferons, denileukin diftitox (Ontak, Ligand Pharmaceuticals Inc.) and cytotoxic chemotherapy. Bexarotene has also been investigated in the treatment of breast cancer and non-small cell carcinoma of the lung with promising early results.     

Etiology,diagnosis, and treatment recommendations for central hypothyroidism associated with bexarotene therapy for cutaneous T-cell lymphoma

Bexarotene is a synthetic retinoid X receptor (RXR)-selective retinoid recently approved for treatment of cutaneous T-cell lymphoma. In clinical trials, bexarotene was found to cause severe central hypothyroidism with high frequency, associated with marked reductions in serum concentrations of thyroid-stimulating hormone (TSH) and thyroxine. Further investigation demonstrated a novel mechanism causing this effect, namely reversible, RXR-mediated, thyroid hormone-independent suppression of TSH gene expression. Treatment of patients with bexarotene-induced hypothyroidism commonly requires high doses of thyroid hormone for replacement therapy, often twice the typical doses used to treat more common etiologies of hypothyroidism. These observations suggest that bexarotene probably has two fundamental effects on thyroid function: to suppress TSH production and to increase thyroid hormone metabolic clearance. Recommendations are provided for diagnosis and treatment of this syndrome.     

Bexarotene is effective and safe for treatment of refractory advanced-stage cutaneous T-cell lymphoma: multinational phase II-III trial results.

PURPOSE: Cutaneous T-cell lymphomas (CTCL) are malignancies of T cells appearing as skin lesions and are responsive to retinoid therapy. Safety and efficacy of a novel RXR-selective retinoid (rexinoid) bexarotene (Targretin, LGD1069; Ligand Pharmaceuticals Inc, San Diego, CA) was evaluated as a single-agent oral therapy administered once daily in an open-label study in patients with refractory advanced-stage CTCL. PATIENTS AND METHODS: Ninety-four patients with biopsy-confirmed CTCL in advanced stages (IIB-IVB) were enrolled at 26 centers. Fifty-six patients received an initial dose of 300 mg/m2/d oral bexarotene and 38 started at more than 300 mg/m2/d. RESULTS: Clinical complete and partial responses were reported by Primary End point Classification for the study in 45% (25 of 56) of patients enrolled at 300 mg/m2/d dosing. At more than 300 mg/m2/d, 55% (21 of 38) of patients responded, including 13% (five of 38) clinical complete. For the 300 mg/m2/d initial dose group, the rate of relapse after response was 36% and the projected median duration of response was 299 days. Improvements were also seen in overall body-surface area involvement, median index lesion surface area, adenopathy, cutaneous tumors, pruritus, and CTCL-specific quality of life. The most frequent drug-related adverse events included hypertriglyceridemia (associated rarely with pancreatitis), hypercholesterolemia, hypothyroidism, and headache. CONCLUSION: Bexarotene is the first in a novel class of pharmacologic agents, the RXR-selective retinoids, or rexinoids. Bexarotene is orally administered, safe, and generally well tolerated with reversible side effects, and is effective for the treatment of advanced, refractory CTCL.     

Induction of apoptosis by bexarotene in cutaneous T-cell lymphoma cells: relevance to mechanism of therapeutic action.

PURPOSE: Bexarotene is the first synthetic rexinoid approved for the treatment of all stages of cutaneous T-cell lymphoma (CTCL) however the mechanism of bexarotene action is unknown. We examined the effects of bexarotene on induction of apoptosis and expression of its cognate receptors in well-established CTCL cell lines (MJ, Hut78, and HH). EXPERIMENTAL DESIGN: CTCL cells were treated with 0.1, 1, and 10 microM bexarotene for 24, 48, 72, and 96 h. Apoptosis was determined by flow-cytometry analysis of sub-G(1) hypodiploid nuclei and annexin V binding populations. Apoptosis-associated proteins and retinoid receptors were detected by Western blots. RESULTS: Bexarotene treatment at 1 and 10 microM for 96 h increased the number of cells with sub-G1 populations and annexin V binding in a dose-dependent manner compared with vehicle controls (DMSO) in all three cell lines, respectively. Bexarotene treatment suppressed the expression of retinoid X receptor alpha and retinoic acid receptor alpha proteins in all three lines compared with untreated controls. Bexarotene treatment decreased the protein levels of survivin, activated caspase-3, and cleaved poly(ADP-Ribose) polymerase, but had no obvious effect on expression of Fas/Fas ligand and bcl-2 proteins in all three CTCL lines. CONCLUSIONS: Bexarotene treatment at clinically relevant concentrations causes apoptosis of CTCL cell lines in association with activation of caspase-3 and cleavage of poly(ADP-Ribose) polymerase, as well as down-regulation of retinoid X receptor alpha, retinoic acid receptor alpha, and survivin. These findings support apoptosis as a mechanism for bexarotene therapy in CTCL.     

Bexarotene in Patients With Peripheral T-cell Lymphomas: Results of a Retrospective Study

Background

Peripheral T-cell lymphomas (PTCLs) are generally aggressive non-Hodgkin lymphomas that portend poor prognosis with currently available therapies. Bexarotene, a retinoic acid derivative, has efficacy in cutaneous T-cell lymphomas, but its activity in PTCL is unknown.

Bexarotene and DAB389IL-2 (Denileukin Diftitox,ONTAK) in Treatment of Cutaneous T-Cell Lymphomas: Algorithms

Mycosis fungoides (MF), CD4⁺ epidermotropic cutaneous T-cell lymphoma (CTCL), often arises as indolent, inflammatory, chronic, persistent patches and plaques. Conservative and sequential topical therapy patients have the same survival as patients treated with aggressive chemotherapy. Hence, until curative therapy is found, therapies that keep MF in check and prevent progression to more advanced lymphoma may be desirable alternatives and may preserve quality of life. Stage IA patients with stable disease have a very favorable prognosis and often initially receive psoriasis-type therapy. Bexarotene gel, a new topical retinoid X receptor retinoid will resolve MF lesions, reducing dermal T-cell infiltrates when used as a single agent. However, it may be even more effective when combined with topical steroids, with phototherapy (ultraviolet B and psoralen-ultraviolet A), or even with oral bexarotene. The gel may also provide a safe adjunctive therapy for individual lesions that are refractory to other agents, including keratodermas. When more than 10% of the body is involved with CTCL or when adenopathy is present (> stage IB), systemic therapy is indicated. Bexarotene capsules have the advantage of easy oral administration and are extremely effective both for early-stage patients with long-standing extensive plaques and for late-stage patients with Sézary syndrome or large-cell transformation. Monitoring of white blood cell count, lipids, and thyroid function is required. Bexarotene should be tested in combination with interferon-alfa or other therapies such as photopheresis, psoralen-ultraviolet A, and methotrexate and for maintenance after total body skin electron beam. DAB₃₈₉IL-2 is targeted to CD25⁺, the interleukin-2 receptor on activated T cells as measured by the expression of CD25. DAB₃₈₉IL-2 has given complete or partial remission in 30% of highly refractory patients with extensive plaques and disfiguring tumors. Because it is effective in killing T cells that surround dermal vessels, cytokine release may occur and result in capillary leak syndrome. Hence, it will be reserved for more advanced and refractory patients and will require intravenous administration and monitoring. The use of oral bexarotene first to reduce dermal infiltrates prior to DAB₃₈₉IL-2 administration might reduce subsequent side effects imparted by this therapy. With three new highly effective agents in the armamentarium for the treatment of CTCL, new combination treatment algorithms can be tested to achieve maximal benefit and quality of life for these patients.     

Emerging role of rexinoids in non-small cell lung cancer: focus on bexarotene

Although the introduction of third-generation antineoplastic agents in the treatment of non-small cell lung cancer has led to modest improvements in overall patient survival, lung cancer continues to be the leading cause of cancer-related death worldwide, and improved therapies are needed. Retinoids play a critical role in the regulation of cell division, growth, differentiation, and proliferation, and they represent an exciting new avenue for targeted therapy. Several synthetic retinoids that bind to retinoic acid receptors are currently being investigated in a variety of tumor types. However, many of these agents have been associated with cheilitis, skin reactions, severe headache, and hypertriglyceridemia. Synthetic agents that bind specifically to retinoid X receptors are called rexinoids. Bexarotene (Targretin; Ligand Pharmaceuticals; San Diego, CA; http://www.ligand.com) is a novel, multitargeted synthetic rexinoid that is currently being investigated in the treatment of non-small cell lung cancer. Phase I and II studies have demonstrated that bexarotene is safe and well tolerated in this patient population either alone or in combination with chemotherapeutic agents. Patients treated with bexarotene experience manageable adverse events at reduced levels compared with retinoic acid receptor-specific retinoids. Bexarotene in combination with chemotherapeutic agents has demonstrated an encouraging median survival for patients with advanced non-small cell lung cancer compared with historical results with combination chemotherapy alone. Two phase III trials are currently under way to fully characterize the role of bexarotene in the treatment of this disease. The purpose of this review is to explore the rationale for rexinoids in the treatment of malignancies and to discuss the clinical profile of bexarotene in the treatment of non-small cell lung cancer.     

Interactions of bexarotene (LGD1069, Targretin) with the coagulation system

Main purpose  

Bexarotene, (LGD1069, Targretin), is an antitumoral agent used as chemotherapy in the treatment of cutaneous T-cell lymphoma. Therapy with bexarotene is accompanied by adverse events, such as, bleeding, hemorrhage, and coagulopathy     

A phase I pharmacokinetic study of bexarotene with vinorelbine and cisplatin in patients with advanced non-small-cell lung cancer (NSCLC)

Purpose

This is a phase I study of the retinoid X receptor agonist bexarotene (Targretin^®) in combination with the chemotherapeutic drugs cisplatin and vinorelbine and lipid-lowering therapy. This study looked for pharmacokinetic (PK) interactions between the agents in parallel with a phase III study of the combination.

Methods

Patients (n = 26) with advanced-stage non-small-cell lung cancer received intravenous cisplatin 100 mg/m² on day 1 and at 4-week intervals plus intravenous vinorelbine 25 mg/m² weekly. Continuous oral bexarotene therapy (400 mg/m²/day) was initiated at day 4. Lipid-lowering therapy was initiated in all patients due to hypertriglyceridemia associated with bexarotene use. PK profiles of the chemotherapeutic agents were obtained on day 1 (without bexarotene) and during cycles 2–4 (with bexarotene). Vinorelbine (n = 18) and free cisplatin (n = 17) PK parameters in evaluable patients were determined using non-compartmental methods.

Results

Mean vinorelbine and free cisplatin clearance and dose-corrected AUC values with bexarotene were within 20% of respective values without concomitant bexarotene. Bexarotene levels did not vary with or without co-administration of the chemotherapeutic agents. There was no evidence of increased toxicity when bexarotene was co-administered with the chemotherapeutic agents.

Conclusions

Bexarotene does not substantially affect vinorelbine or cisplatin PK, and the combination is well tolerated. The results are consistent with the mechanisms of elimination of vinorelbine (high metabolic clearance) and cisplatin (non-enzymatic and renal elimination).

     

Bexarotene is active against subcutaneous panniculitis-like T-cell lymphoma in adult and pediatric populations

IntroductionSubcutaneous panniculitis-like T-cell lymphoma (SPTL-AB) and cutaneous gamma/delta T-cell lymphoma (CGD-TCL) are rare T-cell lymphomas with varying clinical courses. There is no standard treatment, although chemotherapy and hematopoietic stem cell transplantation are commonly used. We describe results using bexarotene for children and adults with these disorders.MethodsWe identified 15 patients (12 adults, 3 children) who were treated with bexarotene between 2000 and 2010 from the Memorial Sloan-Kettering Cancer Center lymphoma database, the Stanford Cancer Center Registry, and the National Cancer Institute (NCI) pediatric lymphoma database. There were 8 females and 7 males, with a median age of 45 years (range, 3 years to 85 years). All patients had stage IV disease. Two of 15 and 4 of 15 patients had documented CGD-TCL and SPTL-AB, respectively; others were presumed to have SPTL-AB. Bexarotene was administered at flat doses corresponding to 91 to 339 mg/m²/d. Two of 15 patients received concurrent denileukin diftitox. Two children received bexarotene as maintenance therapy and were not evaluable for response.ResultsAmong those treated with bexarotene alone, the overall response rate (ORR) was 82% (6/11 complete response [CR], 3/11 partial response [PR]). One of the 2 patients treated with concomitant denileukin diftitox responded for an ORR of 10/13 (77%), including 54% CR and 23% PR. Median progression-free survival was 38.4 months; median duration of response was 26.3 months. Six patients developed hypothyroidism and 9 developed hyperlipidemia; one patient developed dose-limiting hypertriglyceridemia. One pediatric patient developed insulin-dependent diabetes mellitus.ConclusionsIn this retrospective series, bexarotene showed a high response rate in SPTL-AB and CGD-TCL. It was generally well-tolerated with durable responses; therefore, bexarotene represents a promising therapy for children and adults with these disorders.     

Results of a phase II trial of oral bexarotene (Targretin) combined with interferon alfa-2b (Intron-A) for patients with cutaneous T-cell lymphoma

BACKGROUND: Bexarotene is one of the most active single agents for the treatment of recurring or refractory cutaneous T-cell lymphoma (CTCL). Interferon alfa has also been used for many years as an effective treatment for this disease. The results in recent case reports of the combination of bexarotene and interferon alfa have been promising. Based on more extensive results reported with the combination of other retinoids with interferon alfa, the present study attempted to determine the response rate, response duration, and safety of bexarotene (Targretin capsules, Ligand Pharmaceuticals, San Diego, Calif) alone and then with the addition of interferon alfa-2b (Intron-A, Schering-Plough, Kenilworth, NJ). METHODS: Patients with biopsy-proven CTCL, TNM stages IB, IIA, IIB-IV, were treated with oral bexarotene 300 mg/m2/day for at least 8 weeks. If a complete response was not seen after 8 weeks, interferon alfa-2b 3 million units (MU) subcutaneously was added, and increased to 5 MU if tolerated, 3 times a week. RESULTS: A total of 22 patients were enrolled at 5 sites, and 18 patients were assessable for response. Overall response rate for combined bexarotene and interferon alfa was 39% (95% confidence interval [CI]: 17%-64%), including 1 patient with a clinical complete response, 6 patients with partial response, 3 patients with stable disease, and 8 patients with progressive disease. Three partial responses were first noted during the bexarotene-alone phase. Adverse events were generally manageable, and only 1 patient was withdrawn from study for hypertriglyceridemia. CONCLUSIONS: The addition of interferon alfa-2b did not increase the response rate that would have been expected with bexarotene alone.     

Multi-institutional phase I/II trial of oral bexarotene in combination with cisplatin and vinorelbine in previously untreated patients with advanced non-small-cell lung cancer.

PURPOSE: Bexarotene (Targretin; Ligand Pharmaceuticals, Inc, San Diego, CA) is a retinoid-X-receptor (RXR)-selective retinoid with preclinical antitumor activity in squamous cell cancers. In this phase I/II trial, we combined bexarotene with cisplatin and vinorelbine in the treatment of patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-three patients who had stage IIIB NSCLC with pleural effusion or stage IV NSCLC and had received no prior therapy received bexarotene in combination with cisplatin (100 mg/m2) and vinorelbine (alternating doses of 30 mg/m2 and 15 mg/m2). In the phase I portion, the daily dose of bexarotene was escalated in cohorts of three patients from 150 mg/m2 to 600 mg/m2, beginning 1 week before the start of the cisplatin-vinorelbine regimen. Once the maximum-tolerated dose (MTD) of bexarotene was determined, the study entered the phase II portion. Response rate was the primary end point; median survival time and 1-year survival rate were secondary end points. RESULTS: In the phase I portion, the daily MTD of bexarotene was determined to be 400 mg/m2. Eight of 43 patients exhibited major responses. Seven (25%) of the 28 patients in the phase II portion responded to treatment. The median survival time in the phase II portion was 14 months; nine (32%) of the 28 patients were still alive at a minimum follow-up of 2 years. One-year and projected 3-year survival rates were 61% and 30%, respectively. The most common grade 3 and 4 adverse events were hyperlipemia, leukopenia, nausea, vomiting, pneumonia, dyspnea, anemia, and asthenia. Grade 3 and 4 laboratory abnormalities with incidences greater than 5% were decreased hemoglobin levels and WBC, absolute neutrophil, and absolute lymphocyte counts and increased prothrombin time and creatinine and amylase levels. Of the two cases of pancreatitis, one required hospitalization and both were associated with increased triglyceride levels. There was one death secondary to renal insufficiency unrelated to bexarotene treatment. CONCLUSION: In patients with advanced NSCLC, bexarotene with cisplatin and vinorelbine yielded acceptable phase II response rates (25%) and was associated with better-than-expected survival (14-month median survival time; 61% 1-year, 32% 2-year, and 30% projected 3-year survival rates). The regimen should be studied in larger clinical trials.     

Denileukin diftitox: a concise clinical review

Denileukin diftitox (DAB₃₈₉IL-2; Ontak^®) is a novel recombinant fusion protein approved by the US Food and Drug Administration for the treatment of relapsed or refractory cutaneous T-cell lymphoma. It consists of fragments of diphtheria toxin linked to human interleukin-2 and works by targeting the high-affinity interleukin-2 receptor expressed on malignant cells. This article will review the clinical trials leading to the approval of denileukin diftitox for cutaneous T-cell lymphoma, and discuss the potential future role of this novel drug in patients with both malignant and nonmalignant diseases, including non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, solid tumors, psoriasis and graft-versus-host disease.     

Maintenance therapy in cutaneous T-cell lymphoma: Who,when, what?

The aim of current therapy for cutaneous T-cell lymphoma (CTCL) is to induce clinically meaningful remission, provide symptom relief, improve patient quality of life (QoL) and prolong disease-free and overall survival. A key research question is whether such remissions or minimal disease status can be maintained in the long term. There have been few formal studies of maintenance therapy in CTCL. Some skin-directed therapies such as total-skin electron-beam therapy and high-dose psoralen plus ultraviolet A may not be considered suitable, because of the risk of long-term cumulative toxicities. Other therapies such as nitrogen mustard, interferon (IFN)-alpha and bexarotene have demonstrated positive effects in prolonging remissions in small numbers of patients. Large longitudinal studies are required to investigate the efficacy of maintenance treatments in CTCL and their impact on patients' QoL and overall survival. Of the systemic therapies currently approved for the treatment of CTCL, bexarotene and IFN-alpha are obvious candidates for testing, because they can be self-administered by the patient and provide good long-term tolerability.     

Overview of cutaneous T-cell lymphoma: prognostic factors and novel therapeutic approaches

The cutaneous T-cell lymphomas (CTCL) comprise a heterogeneous group of entities. The WHO classification distinguishes indolent low-risk entities, including mycosis fungoides/Sézary syndrome (MF/SS), from aggressive entities, including peripheral T-cell lymphoma and its variants and HTLV-1 associated acute T-cell leukemia/lymphoma. Mycosis fungoides represents the most benign of the cutaneous T-cell lymphomas, with 10-year relative survival ranging from 100% to 41%, depending on the degree of skin involvement. Probability of progression to extracutaneous disease within 20 years of diagnosis can be up to 40%, depending on stage. Treatment strategies for early stage CTCL include topical therapies with or without interferon-alpha or oral agents, while advanced stage patients often progress and are treated with chemotherapy and novel agents. Multiagent cytotoxic regimens are palliative with no demonstrated survival benefit. Among the novel therapies for CTCL is bexarotene, a retinoid X-receptor (RXR)-selective agonist, which has demonstrated efficacy in advanced refractory CTCL. Other novel agents include the interleukin (IL)-2 fusion toxin (ONTAK), pentostatin (a potent adenosine deaminase inhibitor), histone deacetylase inhibitors such as depsipeptide, NF-kappaB inhibitors, cytokine receptor antagonists, immunomodulatory therapies and allogeneic stem cell therapy. The value of new therapeutic approaches to CTCL urgently needs to be assessed.     

Differentiation syndrome in non-M3 acute myeloid leukemia treated with the retinoid X receptor agonist bexarotene

Differentiation Syndrome, also known as all-trans retinoic acid (ATRA) syndrome, is a well-described clinical phenomenon occurring in patients with the M3 subtype of acute myeloid leukemia receiving ATRA chemotherapy. Bexarotene is a novel synthetic compound that selectively binds and activates retinoic X receptors, a subclass of retinoid receptors not targeted by ATRA. We report a patient with refractory non-M3 acute promyelocytic leukemia (AML) who developed differentiation syndrome during bexarotene monotherapy. This case emphasizes the importance of monitoring for differentiation syndrome among patients receiving retinoid therapies and demonstrates the ability of bexarotene to stimulate differentiation of leukemic blasts.     

Cutaneous T-cell lymphomas: Focusing on novel agents in relapsed and refractory disease

Patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL) display a dismal prognosis and their therapy represents an unmet medical need, as the best treatment strategy is yet to be determined. Exciting data on novel targeted agents are now emerging from recently concluded and ongoing clinical trials in patients with relapsed and refractory CTCL. Three FDA approved compounds are used as single agents including the oral retinoid bexarotene and histone deacetylase inhibitors romidepsin and vorinostat. Brentuximab vedotin, an anti-CD30 drug-conjugated monoclonal antibody, has received from European Commission the orphan designation but has not been approved by EMA yet. Several other molecules have demonstrated their activity in the same context and combination strategies are being explored. Participation in a well designed clinical trial is encouraged, as the introduction of novel agents will continue to expand the therapeutics options available in the management of CTCL.     

Phase II trial of the novel retinoid, bexarotene, and gemcitabine plus carboplatin in advanced non-small-cell lung cancer.

PURPOSE: Platinum-based chemotherapy is the standard treatment for advanced non-small-cell lung cancer (NSCLC). Unfortunately, a plateau in efficacy with currently available agents has been reached. Previous studies of the retinoid, bexarotene, a retinoid X receptor-specific ligand, have indicated that it may improve outcome in advanced NSCLC. PATIENTS AND METHODS: Patients with previously untreated stage IIIB or stage IV disease, a performance status of 0 to 2, and adequate organ status were entered. Treatment consisted of up to six cycles of carboplatin (area under the curve = 5.0 on day 1) and gemcitabine (1,000 mg/m2 on days 1 and 8) administered every 21 days. Bexarotene 400 mg/m2 orally was to be administered continuously beginning on day 1 and until progression of disease. All patients received atorvastatin 10 mg orally beginning before bexarotene. The objective was to demonstrate a 1-year survival rate of more than 50%. RESULTS: Forty-eight patients were entered; all were assessable for survival, and 47 were assessable for toxicity and response. The therapeutic regimen was well tolerated except for hypertriglyceridemia. The median time to progression was 6.7 months, and overall median survival was 12.7 months. There was a 25% response rate and a 1-year survival rate of 53%. These results were compared with the outcome of 33 patients treated at our institution with two-drug, platinum-based chemotherapy on controlled trials with similar entry criteria in the previous 5 years. CONCLUSION: Bexarotene can be safely added to platinum-based chemotherapy provided that there is aggressive prophylaxis of hypertriglyceridemia. The median time to progression and overall survival are promising and warrant further evaluation of bexarotene in advanced NSCLC.     

What's new in the management of cutaneous T-cell lymphoma?

The aetiology and clinical management of primary cutaneous T-cell lymphoma (CTCL) and specifically of mycosis fungoides and Sezary syndrome are poorly defined. Interesting new insights into CTCL disease biology as well as a number of emerging of novel therapeutic interventions make this an increasingly interesting area for dermatologists and oncologists involved in the treatment of CTCL. This review article covers much of this new information including new drugs, such as denileukin diftitox (Ontak) a targeted cytotoxic biological agent, Bexarotene an RXR selective retinoid, anti-CD4 monoclonal antibodies (mAb), new cytotoxics agents and vaccines.     

The Treatment of Cutaneous T-Cell Lymphoma with a Novel Retinoid

The clinical experience with bexarotene for cutaneous T-cell lymphoma (CTCL) at our center is reviewed here. Disease activity assessment was monitored every 4 weeks in all patients. Five target lesions were monitored, an area score was performed, and a CTCL-specific health assessment questionnaire was administered. Four patients with refractory plaque CTCL were treated with bexarotene gel. All target lesions disappeared after 8 weeks of therapy, with recurrences observed in untreated areas. In the follow-up period, no recurrences of the original target lesions were observed. One patient withdrew from the study. Patients with refractory patch/plaque disease were randomized to a high-dose (300 mg/m²) or low-dose (6.5 mg/m²) daily oral regimen of bexarotene. After showing disease progression, the two patients on the low-dose arm were entered into the high-dose arm after 8 weeks. Marked clinical responses were seen in all patients treated. The target lesions showed either complete disappearance or a reduction in lesion size, duration, and scale. No new lesions were noted in patients on high-dose bexarotene. Self-assessments also confirmed the palliative properties of the observed responses. All patients had hypertriglyceridemia despite the concomitant administration of atorvastatin at 60 mg/day. Dose reductions were required to maintain safe lipid levels. Four patients with erythrodermic CTCL were treated with high-dose oral therapy, and all patients showed rapid (within 2 weeks) improvement of erythroderma and symptoms.