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Study |

Prospective Multicenter Study of Pegylated Liposomal Doxorubicin Treatment in Patients With Advanced or Refractory Mycosis Fungoides or Sézary Syndrome FREE

Gaëlle Quereux, MD; Sonia Marques, MD; Jean-Michel Nguyen, MD, PhD; Christophe Bedane, MD, PhD; Michel D’incan, MD, PhD; Olivier Dereure, MD, PhD; Elisabeth Puzenat, MD; Alain Claudy, MD, PhD; Ludovic Martin, MD, PhD; Pascal Joly, MD, PhD; Michele Delaunay, MD; Marie Beylot-Barry, MD, PhD; Pierre Vabres, MD, PhD; Philippe Celerier, MD; Bruno Sasolas, MD; Florent Grange, MD, PhD; Amir Khammari, PhD; Brigitte Dreno, MD, PhD
[+] Author Affiliations

Author Affiliations: Pôle d’Information Médicale, d’Evaluation de Santé Publique du Centre Hospitalier Universitaire, Nantes, France (Dr Nguyen); Departments of Dermatology, Centre Hospitalier Universitaire, Nantes (Drs Quereux, Marques, Khammari, and Dreno), Centre Hospitalier Régional Universitaire, Limoges (Dr Bedane), Hôpital Hôtel Dieu, Clermont Ferrand (Dr D’incan), Hôpital Saint Eloi, Montpellier (Dr Dereure), Centre Hospitalier Régional Universitaire, Besançon (Dr Puzenat), Hôpital E. Herriot, Lyon (Dr Claudy), Centre Hospitalier Régional–Hôpital Porte Madeleine, Orleans (Dr Martin), Hôpital Charles Nicolle, Rouen (Dr Joly), Hôpital Saint André, Bordeaux (Dr Delaunay), Hôpital Haut Leveque, Pessac (Dr Beylot-Barry), Hôpital Bocage Sud, Dijon, (Dr Vabres), Centre Hospitalier Le Mans, Le Mans (Dr Celerier), Hôpital Morvan, Brest (Dr Sasolas), and Hospices Civils de Colmar, Colmar (Dr Grange), France.


Arch Dermatol. 2008;144(6):727-733. doi:10.1001/archderm.144.6.727.
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Objective  To assess the rate of objective response to pegylated liposomal doxorubicin hydrochloride (Caelyx) in patients with advanced or refractory cutaneous T-cell lymphoma (CTCL).

Design  Prospective, open, multicenter study.

Setting  Thirteen dermatology departments in France.

Patients  Twenty-five patients with either (1) stage II to stage IV CTCL previously unsuccessfully treated with at least 2 lines of treatments or (2) histologically transformed epidermotropic CTCL requiring chemotherapy.

Intervention  Administration of Caelyx intravenously once every 4 weeks at a dose of 40 mg/m2.

Main Outcome Measures  The response to treatment was evaluated by clinical evaluation.

Results  At the end of treatment, we observed an objective response (primary end point) in 56% of the patients (14 of 25): 5 complete responses and 9 partial responses. The median overall survival time was 43.7 months. For the 14 patients who experienced an objective response, the median progression-free survival time after the end of treatment was 5 months.

Conclusions  This prospective study demonstrates the effectiveness of Caelyx in treating CTCL, with an overall response rate of 56% in spite of the high proportion of patients with advanced-stage disease. Responses were observed in 2 subpopulations of patients in which the prognosis is known to be poorer: Sézary syndrome (overall response rate, 60%) and transformed CTCL (overall response rate, 50%). Moreover, this study shows that dose escalation to 40 mg/m2 does not seem to improve the effectiveness but increases toxic effects (especially hematologic toxic effects) compared with the dose previously tested of 20 mg/m2.

Figures in this Article

Cutaneous T-cell lymphomas (CTCLs) are neoplasias of malignant T lymphocytes. Mycosis fungoides (MF) is the most common type of CTCL and is considered an indolent type. In the early stages (IA and IB), the prognosis is excellent, with survival similar (IA) or close (IB) to that of an age-, sex-, and race-matched population.1 At theses stages, treatments consist of phototherapy, local steroids, or local chemotherapy (nitrogen mustard and carmustine). In more advanced stages (IIB, III, and IV), the prognosis becomes poorer, and the CTCLs are often resistant to treatments. At these stages, most of the guidelines24 recommend as first-line treatments immunomodulators such as interferon-alfa and retinoids or rexinoids, low doses of methotrexate, radiotherapy, and extracorporeal photopheresis (for Sézary syndrome [SS]) to avoid increasing patients' high infection sensitivity.

The second-line recommendations are to use more aggressive systemic therapies such as chemotherapy (cyclophosphamide, cisplatin, vincristine, or etoposide), which cause numerous adverse effects (especially infectious complications and hematologic toxic effects) and have no proven effect on survival.5,6 Among these chemotherapies, doxorubicin hydrochloride is the most commonly used anthracycline for advanced stages of CTCL. It induces hematologic dose-dependent toxic effects and may lead to cardiomyopathy. Pegylated liposomal doxorubicin is a new formulation of doxorubicin encapsulated in liposomes to achieve pharmacokinetic properties such as lower plasma concentration peak, lower clearance, smaller distribution volume, and longer half-life.710 The size of the liposomes allows selective accumulation in the tumor vascular bed, and the pegylation induces reduced clearance by the mononuclear phagocyte system. Increased penetration into the tumor and longer presence owing to liposomal encapsulation could attenuate the toxic effects and allows equal or even enhanced efficacy of the parent anthracycline. In Kaposi's sarcoma, breast cancer, and ovarian cancer,1113 pegylated liposomal doxorubicin has been shown to be less cardiotoxic and nephrotoxic than other forms of doxorubicin.14,15

Wollina et al16 first used pegylated liposomal doxorubicin in 6 patients with CTCL and observed an overall response rate of 83% (4 patients with complete response [CR] and 1 with partial response [PR]) with very few adverse effects (1 case of asymptomatic cardiac ischemia, 1 of viral upper airway infection, 5 of anemia, and 3 of lymphopenia). These results were confirmed in a multicenter retrospective study of 34 patients with CTCL.17 The aim of the present study is to confirm these results in a prospective, open, multicenter study using pegylated liposomal doxorubicin hydrochloride (Caelyx; Schering-Plough, Kenilworth, New Jersey) once every 4 weeks at a dose of 40 mg/m2 in patients with CTCL.

PATIENT ELIGIBILITY

This prospective multicenter study was conducted in 13 dermatology departments in France. The patients were between 18 and 75 years of age, had a performance status of 2 or higher by the Eastern Cooperative Oncology Group (ECOG) criteria,18 and also had a histologically proven CTCL of 1 of the 2 following types: (1) MF and SS, involving stage II (T1-T3N1M0) to stage IV (T1-T4N2-N3M0-M1) disease previously unsuccessfully treated by at least 2 lines of treatment including topical carmustine, topical nitrogen mustard, UV therapy (UV-B and psoralen–UV-A), total body electron therapy, radiotherapy, interferon-alfa, retinoids, monochemotherapy, or polychemotherapy; or (2) transformed MF and SS involving CD30+ or CD30 large cell CTCL requiring chemotherapy. The CTCL subtypes were classified according to the European Organization for Research and Treatment of Cancer (EORTC) criteria,19 and CTCL stages were defined according to the Committee on Staging and Classification of Cutaneous T-Cell Lymphomas.20 We defined Sézary syndrome by using the triad of erythroderma, generalized lymphadenopathy, and the presence of Sézary cells in the peripheral blood. It also had to meet the criteria of the International Society for Cutaneous Lymphomas (ISCL)21: an absolute Sézary cell count of at least 1000 cells/mL, a CD4/CD8 ratio of 10 or higher, an increased number of circulating T cells with aberrant marker expression, and evidence of T-cell clones in the peripheral blood detected by molecular or cytogenetic methods.21

The biological inclusion criteria were a polynuclear neutrophil count higher than 1.5/μL; platelet count higher than 100/μL; aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase concentrations less than 2.5 times those of the upper limit of normal; bilirubin level below the upper limit of normal; and creatinine concentration lower than twice the upper limit of normal. (To convert neutrophils to number of cells × 109/L, multiply by 0.001; platelets to number of cells × 109/L, multiply by 1.0.)

Included patients had to have good heart function (left ventricular ejection fraction ≥50%). The main exclusion criteria were unstable heart disease, history of another malignant neoplasm, active infection, previous treatment with doxorubicin hydrochloride at a cumulative dose higher than 300 mg/m2, previous treatment with doxorubicin without effectiveness, previous treatment with more than 1 line of chemotherapy in CD30+ or CD30 large-cell CTCL, concomitant radiotherapy, and/or pregnancy or current lactation. The ethics committee of Nantes Hospital approved the protocol, and written informed consent was obtained from all the patients.

TREATMENT

Caelyx was administered intravenously once every 4 weeks at a dose of 40 mg/m2. Patients received 8 treatment cycles unless the disease was in progression after the 2 first cycles or in complete remission after the fourth cycle. Treatment was also disrupted by the occurrence of a serious adverse event. If progression occurred after the second cycle, the treatment was stopped. If a complete remission was achieved after 2 doses, the patient received 2 additional doses, and if a patient was in complete remission after 4 doses, the treatment was stopped. However, if the patient was not in complete remission after 4 doses, the treatment was continued until 8 doses had been given.

BASELINE AND FOLLOW-UP MEASUREMENT

At baseline each patient underwent a complete physical examination including performance status evaluation. The following clinical findings were recorded: age, sex, histologic type of the CTCL, stage, and pretreatments. The patients were assessed weekly for hematologic toxic effects and monthly for other toxic effects. Treatment effectiveness was assessed monthly.

ASSESSMENT OF RESPONSE

The main end point was the rate of objective response (CR and PR) after treatment. The secondary end points were to evaluate clinical and biological toxic effects of treatment and duration of response and survival.

Complete response was defined as the clinical and histologic (when possible) disappearance of all lesions. Partial response was defined as a 50% or greater decrease in the number and size of preexisting lesions. Progressive disease (PD) was defined as the appearance of new lesions representing 25% over preexisting lesions, or infiltration of 25% or more of preexisting lesions. Stable disease was defined as any response that did not meet the criteria of CR, PR, or PD. Progression-free survival was defined as the time between the end of treatment and the appearance of a progression. During this time, the patients did not receive any maintenance therapy.

STATISTICAL ANALYSIS

Kaplan-Meier estimates and the log-rank test were used to perform the main efficacy analysis. The log-likelihood ratio test was used to assess different factors. The α risk was set at 5%. All analyses were performed using SAS statistical software, version 9.1 (SAS Institute Inc, Cary, North Carolina).

PATIENTS

Twenty-five patients were enrolled in the study, 14 men and 11 women. Ages ranged from 32 to 77 years (median age, 64 years). The eTable summarizes the clinical data of the 25 patients. Ten patients had nontransformed MF; 5 had SS; 5 had histologically transformed SS; and 5 had histologically transformed MF. Most of the patients (15 of 25) had infiltrated plaques (T3). The others were erythrodermic (T4). The TNM status and tumor stages for all patients are listed in eTable. Pretreatments included topical chemotherapy (carmustine and nitrogen mustard), phototherapy (UV-B and psoralen–UV-A), systemic retinoid, monochemotherapy (methotrexate, chlorambucil, cyclophosphamide, or etoposide), interferon-alfa, x-ray therapy, extracorporeal photopheresis, and polychemotherapy (mostly a combination of cyclophosphamide, vincristine, doxorubicin, and prednisone). All pretreatments are summarized in the eTable.

Table Graphic Jump LocationeTable. Patient Clinical Characteristics
EFFICACY

The numbers of Caelyx doses, responses to treatment, and outcomes are reported in the eTable. Two patients had only 1 Caelyx dose owing to an anaphylactoid reaction during the first perfusion. Two patients dropped out of the trial after 2 doses owing to progressive disease. One patient died after 3 doses due to renal and hepatic acute insufficiencies not related to treatment. In 1 patient, the treatment was stopped after 4 doses owing to a complete remission. Finally, 2 patients had 5 doses; 2 patients had 6 doses; and 2 patients had 7 doses. The other 13 patients had 8 doses.

At the end of treatment, the response rate was 56% (14 of 25), including 5 CRs and 9 PRs. The CR was defined clinically for the 5 patients and was confirmed histologically for 3 of the 5 patients. Nine patients experienced PD during treatment. The overall survival distribution of the 25 patients is shown in Figure 1. The median overall survival time was 43.7 months. Among the 10 patients with SS, 60% had an objective response: 1 CR and 5 PRs. We did not observe any significant difference in response rate according to age (P = .23), sex (P = .90), type of lymphoma (P = .14), histologic transformation (P = .20), stage (P = .33), or prior treatment with systemic chemotherapy (P = .88).

Place holder to copy figure label and caption
Figure 1.

Overall survival of the 25 patients treated with pegylated liposomal doxorubicin hydrochloride. Median survival (solid line) was 43.7 months (95% confidence interval [dotted lines], 23.4-NA). NA indicates not applicable.

Graphic Jump Location

Among the 14 patients who experienced an objective response (CR and PR), the median progression-free survival time after the end of treatment was 5 months (Figure 2), and the median overall survival was 45.8 months. Of the 5 patients who achieved CR with Caelyx treatment, 3 experienced relapse after a median of 358 days (60%).

Place holder to copy figure label and caption
Figure 2.

Progression-free survival of the 14 patients who achieved an objective response (complete or partial) after treatment with pegylated liposomal doxorubicin hydrochloride. Median survival (solid line) was 5.02 months (95% confidence interval [dotted lines], 2.00-NA). NA indicates not applicable.

Graphic Jump Location
ADVERSE EFFECTS

The main toxic effects are summarized in Table 1. Adverse effects rated grade 1 or higher were noted in 80% of the patients (mostly grade 1 and 2, World Health Organization classification). The most frequent adverse events were anemia (36%; n = 9), asthenia (20%; n = 5), nausea and vomiting (20%; n = 5), palmoplantar erythrodysesthesia (12%; n = 3), neutropenia (12%; n = 3), and stomach pain (12%; n = 3). There was no episode of febrile neutropenia during the treatment. Two grade 4 adverse events were noted and occurred in the same patient: hyperthermia associated with hemophagocytosis. Two patients experienced a cardiovascular toxic event: an auriculoventricular block (grade 3) and a decrease in left ventricular ejection fraction to below 50% (grade 2). Two patients experienced serious infections, in 1 case multiple infections, during treatment. The first patient contracted Staphylococcus aureus septicemia (grade 3) after the third dose of Caelyx. The other patient experienced pneumopathy (grade 3) after 4 doses, and 2 episodes of S aureus septicemia (grade 3), 1 after 7 doses and 1 after 8 doses of Caelyx. Neither of these patients experienced neutropenia during treatment nor during the course of the infections.

Table Graphic Jump LocationTable 1. Adverse Events Experienced by Patients During Caelyxa Treatment

We report the first prospective multicenter study to our knowledge on pegylated liposomal doxorubicin in the treatment of CTCL. The 25 patients included had CTCL stage IIB to IVB disease recalcitrant to previous treatment. We observed a response rate of 56% (14 of 25) (20% CR [n = 5] and 36% PR [n = 9]). These results confirm the effectiveness of pegylated liposomal doxorubicin in treating CTCL that was reported in 2 separate studies by Wollina et al.16,17 In the first study, involving 6 patients,16 83% achieved objective response (66% CR and 16% PR); in the second, involving 34 patients,17 88% achieved objective response (44% CR and 44% PR). The response rate was lower in the present study, and there are several possible reasons for the difference. First, patients in our study had more advanced CTCL. The first prior study16 included 3 patients with stage IB disease (T2N0M0) and 3 patients with stage IIB disease (T3N0-N1M0); the second earlier study17 included mainly patients with T1 to T3 disease (only 2 of 34 patients had T4 status), while 10 of our 25 patients had T4 status. Moreover, none of the patients in the earlier studies16,17 had histologically transformed CTCL; in contrast, 10 of our 25 patients had transformed CTCL.

Second, important differences exist between the patients in our study and those of the earlier studies16,17 in terms of prior therapies. In the first study by Wollina et al,16 only 1 of 6 patients (16%) had been treated with chemotherapy before undergoing pegylated liposomal doxorubicin treatment. In the second earlier study,17 20% of the patients had undergone prior chemotherapy. In contrast, 60% of our patients had been treated by chemotherapy before receiving Caelyx.

The retrospective study by Di Lorenzo et al22 of 10 patients with stage IVB MF (T1-T4N0-N3M1) confirms that objective response is poorer in more advanced stage disease. Indeed, these authors observed a 33% partial objective response as opposed to 25% stable disease and 42% PD.

In addition to these few studies assessing the efficacy of pegylated liposomal doxorubicin in the treatment of CTCL, Tsatalas et al23 reported a long-term complete clinical response to pegylated liposomal doxorubicin in 1 case of resistant tumor-stage MF. Also, Prince el al24 reported 1 case of stage IB MF and 1 of SS, both previously refractory to intravenous chemotherapy, in which the disease progressed during treatment with pegylated liposomal doxorubicin.

It is important to note that a potential bias might be introduced into our study by prior treatment response and/or treatment-refractory disease because most of the patients were not treatment-naïve patients. However, it is well known that patients previously treated by other treatments and especially chemotherapies are more difficult to cure.

One interesting point in our study was the efficacy of Caelyx in 2 subgroups of patients with CTCL for whom it had never been studied previously: SS and transformed CTCL. In 10 patients with SS, we observed a high response rate (60%; n = 6), including 1 CR (10%; n = 1). The median progression-free survival time for responding patients with SS was 2 months. All patients except 1 had been previously treated with at least 2 lines of treatments, including topical carmustine, topical nitrogen mustard, UV therapy, total body electron therapy, radiotherapy, interferon-alfa, retinoids, monochemotherapy, or polychemotherapy. The median number of lines of pretreatments was 3, and 70% of the patients with SS had been previously treated by chemotherapy (n = 7).

Patients with transformed CTCL classically have a poor prognosis and low response rates to most therapies.2527 In these patients, we observed a high response rate (50% n = 5) including 1 CR (10%). The median progression-free survival time for these patients with transformed CTCL who obtained an objective response with Caelyx was 2 months, and the patient who obtained a CR is still disease free after 3 years.

We observed a higher rate of toxic effects in our study than was reported by Wollina et al,17 which is probably owing to the fact that our study was prospective. In particular, we observed more anemia (36% vs 9%), more asthenia (20% instead of 0%), more nausea and vomiting (20% instead of 3%), and more mucitis (8% instead of 3%). Eighty percent (38 of 47) of the adverse events observed during the treatment were grade 1 or 2; 14% (7 of 47) were grade 3 (1 anemia, 1 asthenia, 3 septicemia, 1 cutaneous ulceration, 1 pneumopathy, and 1 auriculoventricular block); and 4% (2 of 47) were grade 4. These results can probably be explained by the difference in doses because the adverse effects with this molecule are known to be dose dependent.28 Wollina et al17 used 20 mg/m2 as the dose for 28 patients in their study, 20 to 30 mg/m2 for 4 patients, and 40 mg/m2 for 2 patients, whereas all of our patients received a dose of 40 mg/m2. In our study we observed 4 serious infections (3 cases of S aureus septicemia and 1 pneumopathy). These infections are well-known adverse effects of chemotherapy but had never been reported in patients with CTCL receiving pegylated liposomal doxorubicin. These findings emphasize the need for caution when treating patients who have a high risk of infection due to their cutaneous lymphoma. The only patient who experienced a grade 4 adverse effect in our study had an unexplained association of hyperthermia, face edema, and spontaneously regressive hemophagocytosis.

Other chemotherapies tested in advanced or refractory CTCL are listed in Table 2.6,2950,52 These treatments are most often used as monochemotherapies. Fludarabine has been used in 4 studies in advanced CTCL,2932 with an overall response rate of 20% to 51% and a higher response rate when combined with extracorporeal photopheresis (63%).32 Methotrexate has been tested for the same indication in 4 studies.3336 The best response rates were obtained in erythrodermic CTCL (58%33 and 76%34) and the worst ones in T3 disease. Gemcitabine has been evaluated in 2 studies in the treatment of advanced or refractory CTCL and showed response rates of 70%37 and 75%.38 Several studies have suggested the effectiveness of pentostatin in pretreated CTCL with response rates ranging from 33% to over 70%.3944 Chlorambucil was used in erythrodermic CTCL45,46; it was combined with corticosteroids, and the response rate was 100%, with a median duration of response of 12 months in 1 study.46 One study assessing the effectiveness of temozolomide in pretreated stage IIB to stage III CTCL reported a response rate of 33%.47

Table Graphic Jump LocationTable 2. Chemotherapies Used for the Treatment of Advanced or Refractory Cutaneous T-Cell Lymphoma

Polychemotherapy is also frequently used in refractory CTCL. The most common regimens are CHOP (containing cyclophosphamide, vincristine, doxorubicin, and prednisone), COP (containing cyclophosphamide, vincristine, and prednisone), and EPOCH (containing etoposide, cyclophosphamide, vincristine, doxorubicin, and prednisone). In the very few controlled studies of these polychemotherapy regimens,4852 the overall response rates range from 40% to 100%.

It is difficult to compare the results of these studies, some of them being prospective and others retrospective. Moreover, the methods of assessing response were not the same across studies, and the durations of response were not calculated in the same way. For the studies of methotrexate,3336 the time to treatment failure was evaluated starting with the first day of treatment to the failure of the treatment, and the treatment was ongoing. For other studies such as those of gemcitabine,37,38 the end point was the time of complete or partial remission after treatment completion. In the studies of Quaglino et al32 and Akpek et al,51 the end points were the time to progression defined from the first day of treatment to the progression. For the temozolomide study,47 the follow-up was very short (6-9 months), explaining the reported short duration of response. And for the oldest studies,45,50 the duration of response was not specified.

In summary, the present prospective study demonstrates the effectiveness of pegylated liposomal doxorubicin in treating CTCL, showing a response rate of 53% in refractory, frequently advanced cases. Therefore, pegylated liposomal doxorubicin can be one of the choices in the treatment of CTCL. This treatment was also effective in 2 subpopulations of patients for whom the prognosis is known to be poorer: patients with SS and those with transformed CTCL. Moreover this study shows that if the dose is increased to 40 mg/m2, effectiveness is not improved, but toxic effects (especially hematologic) are increased compared with the dose of 20 mg/m2.

Correspondence: Brigitte Dreno, PhD, Department of Dermatology, Centre Hospitalier Universitaire Hotel Dieu, Place Alexis Ricordeau, 44035 Nantes Cedex 01, France.

Accepted for Publication: October 12, 2007.

Author Contributions: Drs Khammari and Dreno had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Khammari and Dreno. Acquisition of data: Quereux, Marques, Bedane, D’incan, Dereure, Puzenat, Claudy, Martin, Joly, Delaunay, Beylot-Barry, Vabres, Celerier, Sasolas, Grange, and Khammari. Analysis and interpretation of data: Quereux, Nguyen, Celerier, and Dreno. Drafting of the manuscript: Quereux. Critical revision of the manuscript for important intellectual content: Quereux, Marques, Nguyen, Bedane, D’incan, Dereure, Puzenat, Claudy, Martin, Delaunay, Beylot-Barry, Vabres, Celerier, Sasolas, Grange, Khammari, and Dreno. Statistical analysis: Nguyen. Obtained funding: Dreno. Administrative, technical, and material support: Khammari and Dreno. Study supervision: Khammari and Dreno.

Financial Disclosure: None reported.

Funding/Support: This study was supported by Nantes University Hospital (Dr Dreno). Schering-Plough provided the Caelyx used in this study.

Role of the Sponsors: The sponsors had no role in the design and conduct of the study, in the collection, analysis, or interpretation of data, or in the preparation, review, or approval of the manuscript.

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Dmitrovsky  EMatthews  MJBunn  PA  et al.  Cytologic transformation in cutaneous T-cell lymphoma: a clinicopathologic entity associated with poor prognosis. J Clin Oncol 1987;5 (2) 208- 215
PubMed
Goebel  FDGoldstein  DGoos  MJablonowski  HSiewert  JS Efficacy and safety of Stealth liposomal doxorubicin in AIDS-related Kaposi's sarcoma. Br J Cancer 1996;73 (8) 989- 994
PubMed Link to Article
Von Hoff  DDDahlberg  SHarstock  RJEyre  HJ Activity of fludarabine monophosphate in patients with advanced mycosis fungoides: a Southwest Oncology Group study. J Natl Cancer Inst 1990;82 (16) 1353- 1355
PubMed Link to Article
Foss  FMIhde  DCLinnoila  IR  et al.  Phase II trial of fludarabine phosphate and interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome. J Clin Oncol 1994;12 (10) 2051- 2059
PubMed
Scarisbrick  JJChild  FJClift  A  et al.  A trial of fludarabine and cyclophosphamide combination chemotherapy in the treatment of advanced refractory primary cutaneous T-cell lymphoma. Br J Dermatol 2001;144 (5) 1010- 1015
PubMed Link to Article
Quaglino  PFierro  MTRossotto  GLSavoia  PBernengo  MG Treatment of advanced mycosis fungoides/Sézary syndrome with fludarabine and potential adjunctive benefit to subsequent extracorporeal photochemotherapy. Br J Dermatol 2004;150 (2) 327- 336
PubMed Link to Article
Zackheim  HSEpstein  EH  Jr Low-dose methotrexate for the Sézary syndrome. J Am Acad Dermatol 1989;21 (4, pt 1) 757- 762
PubMed Link to Article
Zackheim  HSKashani-Sabet  MHwang  ST Low-dose methotrexate to treat erythrodermic cutaneous T-cell lymphoma: results in twenty-nine patients. J Am Acad Dermatol 1996;34 (4) 626- 631
PubMed Link to Article
Zackheim  HSKashani-Sabet  MMcMillan  A Low-dose methotrexate to treat mycosis fungoides: a retrospective study in 69 patients. J Am Acad Dermatol 2003;49 (5) 873- 878
PubMed Link to Article
Schappell  DLAlper  JCMc Donald  CJ Treatment of advanced mycosis fungoides and Sézary syndrome with continuous infusions of methotrexate followed by fluorouracil and leucovorin rescue. Arch Dermatol 1995;131 (3) 307- 313
PubMed Link to Article
Zinzani  PLBaliva  GMagagnoli  M  et al.  Gemcitabine treatment in pretreated cutaneous T-cell lymphoma: experience in 44 patients. J Clin Oncol 2000;18 (13) 2603- 2606
PubMed
Marchi  EAlinari  LTani  M  et al.  Gemcitabine as frontline treatment for cutaneous T-cell lymphoma: phase II study of 32 patients. Cancer 2005;104 (11) 2437- 2441
PubMed Link to Article
Dearden  CMatutes  ECatovsky  D Pentostatin treatment of cutaneous T-cell lymphoma. Oncology (Williston Park) 2000;14 (6) ((Suppl 2)) 37- 40
PubMed
Foss  FM Activity of pentostatin (Nipent) in cutaneous T-cell lymphoma: single-agent and combination studies. Semin Oncol 2000;27 (2) ((Suppl 5)) 58- 63
PubMed
Ho  ADSuciu  SStrickmans  P  et al.  Pentostatin in T-cell malignancies-a phase II trial of the EORTC. Ann Oncol 1999;10 (12) 1493- 1498
PubMed Link to Article
Greiner  DOlsen  EAPetroni  G Pentostatin (2'-deoxycoformycin) in the treatment of cutaneous T-cell lymphoma. J Am Acad Dermatol 1997;36 (6, pt 1) 950- 955
PubMed Link to Article
Cassileth  PACheubart  BSpiers  AS  et al.  Pentostatin induces durable remissions in hairy cell leukemia. J Clin Oncol 1991;9 (2) 243- 246
PubMed
Tsimberidou  AMGiles  FDuvic  MFayad  LKurzrock  R Phase II study of pentostatin in advanced T-cell lymphoid malignancies: update of an MD Anderson Cancer Center series. Cancer 2004;100 (2) 342- 349
PubMed Link to Article
Winkelmann  RKDiaz-Perez  JLBuechner  SA The treatment of Sézary syndrome. J Am Acad Dermatol 1984;10 (6) 1000- 1004
PubMed Link to Article
Coors  EAVon Den Driesch  P Treatment of erythrodermic cutaneous T-cell lymphoma with intermittent chlorambucil and fluocortolone therapy. Br J Dermatol 2000;143 (1) 127- 131
PubMed Link to Article
Tani  MFina  MAlinari  LStefoni  VBaccarani  MZinzani  PL Phase II trial of temozolomide in patients with pretreated cutaneous T-cell lymphoma. Haematologica 2005;90 (9) 1283- 1284
PubMed
Fierro  MTDoveil  GCQuaglino  P  et al.  Combination of etoposide, idarubicin, cyclophosphamide, vincristine, prednisone and bleomycin (VICOP-B) in the treatment of advanced cutaneous T-cell lymphoma. Dermatology 1997;194 (3) 268- 272
PubMed Link to Article
Case  DC Combination chemotherapy for mycosis fungoides with cyclophosphamide, vincristine, methotrexate, and prednisone. Am J Clin Oncol 1984;7 (5) 453- 455
PubMed Link to Article
Sentis  HJWillemze  RVan Vlotten  WA Systemic polychemotherapy in patients with mycosis fungoides and lymph node involvement: a follow-up study of 17 patients. Acta Derm Venereol 1985;65 (2) 179- 183
PubMed
Akpek  GKoh  HKBogen  SO’Hara  CFoss  FM Chemotherapy with etoposide, vincristine, doxorubicin, bolus cyclophosphamide, and oral prednisone in patients with refractory cutaneous T-cell lymphoma. Cancer 1999;86 (7) 1368- 1376
PubMed Link to Article
Molin  LThomsen  KVolden  G  et al.  Retinoids and systemic chemotherapy in cases of advanced mycosis fungoides: a report from the Scandinavian Mycosis Fungoides Group. Acta Derm Venereol 1987;67 (2) 179- 182
PubMed

Figures

Place holder to copy figure label and caption
Figure 1.

Overall survival of the 25 patients treated with pegylated liposomal doxorubicin hydrochloride. Median survival (solid line) was 43.7 months (95% confidence interval [dotted lines], 23.4-NA). NA indicates not applicable.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Progression-free survival of the 14 patients who achieved an objective response (complete or partial) after treatment with pegylated liposomal doxorubicin hydrochloride. Median survival (solid line) was 5.02 months (95% confidence interval [dotted lines], 2.00-NA). NA indicates not applicable.

Graphic Jump Location

Tables

Table Graphic Jump LocationeTable. Patient Clinical Characteristics
Table Graphic Jump LocationTable 1. Adverse Events Experienced by Patients During Caelyxa Treatment
Table Graphic Jump LocationTable 2. Chemotherapies Used for the Treatment of Advanced or Refractory Cutaneous T-Cell Lymphoma

References

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Di Lorenzo  GDi trolio  RDelfino  MDe Placido  S Pegylated liposomal doxorubicin in stage IVB mycosis fungoides. Br J Dermatol 2005;153 (1) 183- 185
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Tsatalas  CMartinis  GMargaritis  D  et al.  Long-term remission of recalcitrant tumour-stage mycosis fungoides following chemotherapy with pegylated liposomal doxorubicin. J Eur Acad Dermatol Venereol 2003;17 (1) 80- 82
PubMed Link to Article
Prince  HMSeymour  JFRyan  GMcCormack  C Pegylated liposomal doxorubicin in the treatment of cutaneous T-cell lymphoma. J Am Acad Dermatol 2001;44 (1) 149- 150
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Diamandidou  EColome-Grimmer  MFayad  LDuvic  MKurzrock  R Transformation of mycosis fungoides/Sézary syndrome: clinical characteristics and prognosis. Blood 1998;92 (4) 1150- 1159
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Salhany  KECousar  JBGreer  JPCasey  TTFields  JPCollins  RD Transformation of cutaneous T cell lymphoma to large cell lymphoma: a clinicopathologic and immunologic study. Am J Pathol 1988;132 (2) 265- 277
PubMed
Dmitrovsky  EMatthews  MJBunn  PA  et al.  Cytologic transformation in cutaneous T-cell lymphoma: a clinicopathologic entity associated with poor prognosis. J Clin Oncol 1987;5 (2) 208- 215
PubMed
Goebel  FDGoldstein  DGoos  MJablonowski  HSiewert  JS Efficacy and safety of Stealth liposomal doxorubicin in AIDS-related Kaposi's sarcoma. Br J Cancer 1996;73 (8) 989- 994
PubMed Link to Article
Von Hoff  DDDahlberg  SHarstock  RJEyre  HJ Activity of fludarabine monophosphate in patients with advanced mycosis fungoides: a Southwest Oncology Group study. J Natl Cancer Inst 1990;82 (16) 1353- 1355
PubMed Link to Article
Foss  FMIhde  DCLinnoila  IR  et al.  Phase II trial of fludarabine phosphate and interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome. J Clin Oncol 1994;12 (10) 2051- 2059
PubMed
Scarisbrick  JJChild  FJClift  A  et al.  A trial of fludarabine and cyclophosphamide combination chemotherapy in the treatment of advanced refractory primary cutaneous T-cell lymphoma. Br J Dermatol 2001;144 (5) 1010- 1015
PubMed Link to Article
Quaglino  PFierro  MTRossotto  GLSavoia  PBernengo  MG Treatment of advanced mycosis fungoides/Sézary syndrome with fludarabine and potential adjunctive benefit to subsequent extracorporeal photochemotherapy. Br J Dermatol 2004;150 (2) 327- 336
PubMed Link to Article
Zackheim  HSEpstein  EH  Jr Low-dose methotrexate for the Sézary syndrome. J Am Acad Dermatol 1989;21 (4, pt 1) 757- 762
PubMed Link to Article
Zackheim  HSKashani-Sabet  MHwang  ST Low-dose methotrexate to treat erythrodermic cutaneous T-cell lymphoma: results in twenty-nine patients. J Am Acad Dermatol 1996;34 (4) 626- 631
PubMed Link to Article
Zackheim  HSKashani-Sabet  MMcMillan  A Low-dose methotrexate to treat mycosis fungoides: a retrospective study in 69 patients. J Am Acad Dermatol 2003;49 (5) 873- 878
PubMed Link to Article
Schappell  DLAlper  JCMc Donald  CJ Treatment of advanced mycosis fungoides and Sézary syndrome with continuous infusions of methotrexate followed by fluorouracil and leucovorin rescue. Arch Dermatol 1995;131 (3) 307- 313
PubMed Link to Article
Zinzani  PLBaliva  GMagagnoli  M  et al.  Gemcitabine treatment in pretreated cutaneous T-cell lymphoma: experience in 44 patients. J Clin Oncol 2000;18 (13) 2603- 2606
PubMed
Marchi  EAlinari  LTani  M  et al.  Gemcitabine as frontline treatment for cutaneous T-cell lymphoma: phase II study of 32 patients. Cancer 2005;104 (11) 2437- 2441
PubMed Link to Article
Dearden  CMatutes  ECatovsky  D Pentostatin treatment of cutaneous T-cell lymphoma. Oncology (Williston Park) 2000;14 (6) ((Suppl 2)) 37- 40
PubMed
Foss  FM Activity of pentostatin (Nipent) in cutaneous T-cell lymphoma: single-agent and combination studies. Semin Oncol 2000;27 (2) ((Suppl 5)) 58- 63
PubMed
Ho  ADSuciu  SStrickmans  P  et al.  Pentostatin in T-cell malignancies-a phase II trial of the EORTC. Ann Oncol 1999;10 (12) 1493- 1498
PubMed Link to Article
Greiner  DOlsen  EAPetroni  G Pentostatin (2'-deoxycoformycin) in the treatment of cutaneous T-cell lymphoma. J Am Acad Dermatol 1997;36 (6, pt 1) 950- 955
PubMed Link to Article
Cassileth  PACheubart  BSpiers  AS  et al.  Pentostatin induces durable remissions in hairy cell leukemia. J Clin Oncol 1991;9 (2) 243- 246
PubMed
Tsimberidou  AMGiles  FDuvic  MFayad  LKurzrock  R Phase II study of pentostatin in advanced T-cell lymphoid malignancies: update of an MD Anderson Cancer Center series. Cancer 2004;100 (2) 342- 349
PubMed Link to Article
Winkelmann  RKDiaz-Perez  JLBuechner  SA The treatment of Sézary syndrome. J Am Acad Dermatol 1984;10 (6) 1000- 1004
PubMed Link to Article
Coors  EAVon Den Driesch  P Treatment of erythrodermic cutaneous T-cell lymphoma with intermittent chlorambucil and fluocortolone therapy. Br J Dermatol 2000;143 (1) 127- 131
PubMed Link to Article
Tani  MFina  MAlinari  LStefoni  VBaccarani  MZinzani  PL Phase II trial of temozolomide in patients with pretreated cutaneous T-cell lymphoma. Haematologica 2005;90 (9) 1283- 1284
PubMed
Fierro  MTDoveil  GCQuaglino  P  et al.  Combination of etoposide, idarubicin, cyclophosphamide, vincristine, prednisone and bleomycin (VICOP-B) in the treatment of advanced cutaneous T-cell lymphoma. Dermatology 1997;194 (3) 268- 272
PubMed Link to Article
Case  DC Combination chemotherapy for mycosis fungoides with cyclophosphamide, vincristine, methotrexate, and prednisone. Am J Clin Oncol 1984;7 (5) 453- 455
PubMed Link to Article
Sentis  HJWillemze  RVan Vlotten  WA Systemic polychemotherapy in patients with mycosis fungoides and lymph node involvement: a follow-up study of 17 patients. Acta Derm Venereol 1985;65 (2) 179- 183
PubMed
Akpek  GKoh  HKBogen  SO’Hara  CFoss  FM Chemotherapy with etoposide, vincristine, doxorubicin, bolus cyclophosphamide, and oral prednisone in patients with refractory cutaneous T-cell lymphoma. Cancer 1999;86 (7) 1368- 1376
PubMed Link to Article
Molin  LThomsen  KVolden  G  et al.  Retinoids and systemic chemotherapy in cases of advanced mycosis fungoides: a report from the Scandinavian Mycosis Fungoides Group. Acta Derm Venereol 1987;67 (2) 179- 182
PubMed

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