 |
[Home] | [Search] | [Medical Q&A Forums] | [Patient Network] |
This information has been brought to you by
Med Help International,
licenced by the National Cancer Institute as a distributor of CancerNet.
CancerMail from the National Cancer Institute
******************************************************************************
* This information is intended mainly for use by doctors and other health *
* care professionals. If you have questions about this topic, you can ask *
* your doctor, or call the Cancer Information Service at 1-800-4-CANCER *
* (1-800-422-6237). *
******************************************************************************
Information from PDQ -- for Health Professionals
Mycosis fungoides/Sezary syndrome
208/10830
** GENERAL INFORMATION **
Note: This summary was previously titled Cutaneous T-cell Lymphoma. It has
been renamed because it focuses on only 2 types of cutaneous T-cell lymphomas:
mycosis fungoides and the Sezary syndrome.
Mycosis fungoides and the Sezary syndrome (MF/SS) are neoplasias of malignant
T-lymphocytes that usually possess the helper/inducer cell surface phenotype.
These neoplasms initially present as skin involvement and as such have been
classified as cutaneous T-cell lymphomas. These lymphomas are included in the
Revised European-American Lymphoma (REAL) classification as low grade T-cell
lymphomas, which should be distinguished from other T-cell lymphomas which
involve the skin such as anaplastic large cell lymphoma (CD30 positive),
peripheral T-cell lymphoma (CD30 negative, with no epidermal involvement),
adult T-cell leukemia/lymphoma (usually with systemic involvement), or
subcutaneous panniculitic T-cell lymphoma.[1,2] These other histologic types
of T-cell lymphomas are discussed in another PDQ summary. (Refer to the PDQ
summary on Adult Non-Hodgkin's Lymphoma Treatment for more information.) In
addition, a number of benign or very indolent conditions can be confused with
mycosis fungoides. Therefore, consultation with a pathologist who has
expertise in distinguishing these conditions is important.[3]
The prognosis of patients with MF/SS is based on the extent of disease at
presentation (stage).[4] The presence of lymphadenopathy and involvement of
peripheral blood and viscera increase in likelihood with worsening cutaneous
involvement and define poor prognostic groups.[5] The median survival
following diagnosis varies according to stage. Patients with stage IA disease
have a median survival of 20 or more years. The majority of deaths for this
group are not caused by, nor are they related to, MF.[6] In contrast, more
than half of patients with stage III through IV disease die of MF, with a
median survival of less than 5 years.[4-6]
Typically, the natural history of MF is indolent.[7] Symptoms of the disease
may present for long periods (average of 2-10 years) as waxing and waning
cutaneous eruptions prior to biopsy confirmation. MF/SS is treatable with
available topical and/or systemic therapies. However, curative modalities have
thus far proven elusive, with the possible exception of patients with minimal
disease confined to the skin.
Cutaneous disease typically progresses from an eczematous patch/plaque stage
covering less than 10% of the body surface (T1) to plaque stage covering
greater than or equal to 10% of the body surface (T2), and finally to tumors
(T3) which frequently undergo necrotic ulceration.[3,8] SS is an advanced form
of MF with generalized erythroderma (T4) and peripheral blood involvement at
presentation. Cytologic transformation from a low-grade to a high-grade
lymphoma sometimes occurs during the course of these diseases and is associated
with a poor prognosis.[9-11] A common cause of death during the tumor phase is
sepsis from Pseudomonas aeruginosa or Staphylococcus aureus due to chronic skin
infection with staph species and subsequent systemic infections.[8]
References:
1. Willemze R, Kerl H, Sterry W, et al.: EORTC classification for primary
cutaneous lymphomas: a proposal from the Cutaneous Lymphoma Study Group
of the European Organization for Research and Treatment of Cancer.
Blood 90(1): 354-371, 1997.
2. Harris NL, Jaffe ES, Stein H, et al.: A revised European-American
classification of lymphoid neoplasms: a proposal from the International
Lymphoma Study Group. Blood 84(5): 1361-1392, 1994.
3. Siegel RS, Pandolfino T, Guitart J, et al.: Primary cutaneous T-cell
lymphoma: review and current concepts. Journal of Clinical Oncology
18(15): 2908-2925, 2000.
4. Zackheim HS, Amin S, Kashani-Sabet M, et al.: Prognosis in cutaneous
T-cell lymphoma by skin stage: long-term survival in 489 patients.
Journal of the American Academy of Dermatology 40(3): 418-425, 1999.
5. de Coninck EC, Kim YH, Varghese A, et al.: Clinical characteristics and
outcome of patients with extracutaneous mycosis fungoides. Journal of
Clinical Oncology 19(3): 779-784, 2001.
6. Kim YH, Jensen RA, Watanabe GL, et al.: Clinical stage IA (limited patch
and plaque) mycosis fungoides: a long-term outcome analysis. Archives
of Dermatology 132(11): 1309-1313, 1996.
7. Diamandidou E, Cohen PR, Kurzrock R: Mycosis fungoides and Sezary
syndrome. Blood 88(7): 2385-2409, 1996.
8. Lorincz AL: Cutaneous T-cell lymphoma (mycosis fungoides). Lancet
347(9005): 871-876, 1996.
9. Schechter GP, Sausville EA, Fischmann AB, et al.: Evaluation of
circulating malignant cells provides prognostic information in cutaneous
T-cell lymphoma. Blood 69(3): 841-849, 1987.
10. Dmitrovsky E, Matthews MJ, Bunn PA, et al.: Cytologic transformation in
cutaneous T cell lymphoma: a clinicopathologic entity associated with
poor prognosis. Journal of Clinical Oncology 5(2): 208-215, 1987.
11. Kim YH, Bishop K, Varghese A, et al.: Prognostic factors in erythrodermic
mycosis fungoides and the Sezary syndrome. Archives of Dermatology
131(9): 1003-1008, 1995.
** CELLULAR CLASSIFICAITON **
The histologic diagnosis of mycosis fungoides and the Sezary syndrome (MF/SS)
is usually difficult in the initial stages of the disease and may require the
review of multiple biopsies by an experienced pathologist.
A definitive diagnosis from a skin biopsy requires the presence of MF/SS cells
(convoluted lymphocytes), a band-like upper dermal infiltrate, and epidermal
infiltrations with Pautrier's abscesses (collections of neoplastic
lymphocytes). A definitive diagnosis of SS may be made from a peripheral blood
evaluation when skin biopsies are consistent with the diagnosis.
** STAGE INFORMATION **
The stages given here are defined by TNM classification. Peripheral blood
involvement with mycosis fungoides or Sezary cells is correlated with more
advanced skin stage, lymph node and visceral involvement, and shortened
survival, but probably provides no independent prognostic information beyond
that associated with TNM staging. In a multivariate analysis, the two most
important prognostic factors are the presence of visceral disease and type of
skin involvement.[1,2]
-- TNM definitions --
Primary tumor (T)
T1: Eczematous patches, papules, or limited plaques covering less than
10% of the skin surface
T2: Erythematous patches, papules, or generalized plaques covering 10% or
more of the skin surface
T3: Tumors, one or more
T4: Generalized erythroderma
Note: Pathology of T1-T4 is diagnostic of cutaneous T-cell lymphoma (CTCL).
When characteristics of more than one T exist, both are recorded and the
highest is used for staging, for example, T4(3).
Nodal involvement (N):
N0: No clinically abnormal peripheral lymph nodes, pathology negative for
CTCL
N1: Clinically abnormal peripheral lymph nodes, pathology negative for CTCL
N2: No clinically abnormal peripheral lymph nodes, pathology positive for
CTCL
N3: Clinically abnormal peripheral lymph nodes, pathology positive for CTCL
Note: The number of sites of abnormal nodes is recorded. For example,
cervical (left + right), inguinal (left + right), epitrochlear,
submandibular, and so forth. A pathologic classification for lymph node
involvement has been developed by Matthews and Gazdar.[3] The degree of
nodal involvement may have prognostic significance when categorized
according to this system.
Distant metastasis (M)
M0: No involvement of visceral organs
M1: Visceral involvement (must have confirmation of pathology; organ
involved should be specified)
Note: The TNM classification includes a subcategory for patients with CTCL:
Blood involvement (B)
B0: <5% atypical lymphocytes
B1: >/=5% atypical lymphocytes
-- Stage I --
Stage IA is defined as the following TNM grouping:
T1, N0, M0
Stage IB is defined as the following TNM grouping:
T2, N0, M0
-- Stage II --
Stage IIA is defined as either of the following TNM groupings:
T1 or T2, N1, M0
Stage IIB is defined as either of the following TNM groupings:
T3, N0 or N1, M0
-- Stage III --
Stage III is defined as either of the following TNM groupings:
T4, N0 or N1, M0
-- Stage IV --
Stage IVA is defined as any of the following TNM groupings:
T1-T4, N2 or N3, M0
Stage IVB is defined as any of the following TNM groupings:
T1-T4, N0-N3, M1
Note: Involvement of peripheral blood is also associated with a shorter
survival and an increased risk of nodal and/or visceral involvement. Some
studies suggest that patients can be divided into three groups: Stage IA, IB,
and IIA, with excellent 5- and 10-year survival; stage IIB and III, with
intermediate survival; and stage IVA and IVB, with poor survival. The survival
of patients with affected lymph nodes is as poor as those with visceral
involvement.
References:
1. Bunn PA, Lamberg SI: Report of the Committee on Staging and
Classification of Cutaneous T-cell Lymphomas. Cancer Treatment Reports
63(4): 725-728, 1979.
2. Schechter GP, Sausville EA, Fischmann AB, et al.: Evaluation of
circulating malignant cells provides prognostic information in cutaneous
T-cell lymphoma. Blood 69(3): 841-849, 1987.
3. Sausville EA, Eddy JL, Makuch RW, et al.: Histopathologic staging at
initial diagnosis of mycosis fungoides and the sezary syndrome:
definition of three distinctive prognostic groups. Annals of Internal
Medicine 109(5): 372-382, 1988.
** TREATMENT OPTIONS OVERVIEW **
Treatment of mycosis fungoides and the Sezary syndrome (MF/SS) includes topical
chemotherapy with mechlorethamine (nitrogen mustard) or carmustine (BCNU),
psoralen and ultraviolet A radiation (PUVA), total-skin electron-beam
irradiation (TSEB), irradiation of symptomatic skin lesions, interferon alfa
alone or in combination with topical therapy, single- and multi-agent
chemotherapy, and combined modality treatment.[1] These treatments produce
remissions, but cure is uncommon and can only be achieved in the earliest stage
of disease. Therefore, treatment is considered palliative for most patients,
although major symptomatic improvement is regularly achieved. However,
survival in excess of 8 years is not uncommon. All patients with MF/SS are
candidates for clinical trials evaluating new approaches to treatment.
Current areas of interest in clinical trials for MF confined to the skin
include combined modality therapies containing both topical and systemic agents
such as TSEB combined with chemotherapy, topical mechlorethamine or PUVA
combined with interferon, or wide-field irradiation techniques with PUVA.
There have been reports of activity for extracorporeal photochemotherapy using
psoralen; interferon gamma or alfa; pentostatin; retinoids; fludarabine;
acyclovir; 2-chlorodeoxyadenosine (2-CdA); serotherapy with unlabeled,
toxin-labeled, or radiolabeled monoclonal antibodies; and cell surface receptor
ligand-toxin fusion protein.[2-10] Combinations of these agents (such as
interferons and retinoids) are also being evaluated.
The designations in PDQ that treatments are "standard" or "under clinical
evaluation" are not to be used as a basis for reimbursement determinations.
References:
1. Bunn PA, Hoffman SJ, Norris D, et al.: Systemic therapy of cutaneous
T-cell lymphomas (mycosis fungoides and the Sezary syndrome). Annals of
Internal Medicine 121(8): 592-602, 1994.
2. Kaplan EH, Rosen ST, Norris DB, et al: Phase II study of recombinant
human interferon gamma for treatment of cutaneous T-cell lymphoma.
Journal of the National Cancer Institute 82(3): 208-212, 1990.
3. Heald P, Rook A, Perez M, et al.: Treatment of erythrodermic cutaneous
T-cell lymphoma with extracorporeal photochemotherapy. Journal of the
American Academy of Dermatology 27(3): 427-433, 1992.
4. Rosen ST, Zimmer AM, Goldman-Leikin R, et al.: Radioimmunodetection and
radioimmunotherapy of cutaneous T cell lymphomas using an 131I-labeled
monoclonal antibody: an Illinois Cancer Council study. Journal of
Clinical Oncology 5(4): 562-573, 1987.
5. Foss FM, Ihde DC, Breneman DL, et al.: Phase II study of pentostatin and
intermittent high-dose recombinant interferon alfa-2a in advanced
mycosis fungoides/Sezary syndrome. Journal of Clinical Oncology 10(12):
1907-1913, 1992.
6. Saven A, Carrera CJ, Carson DA, et al.: 2-Chlorodeoxyadenosine: an active
agent in the treatment of cutaneous T-cell lymphoma. Blood 80(3):
587-592, 1992.
7. Kuzel TM, Roenigk HH, Samuelson E, et al.: Effectiveness of interferon
alfa-2a combined with phototherapy for mycosis fungoides and the Sezary
syndrome. Journal of Clinical Oncology 13(1): 257-263, 1995.
8. Olsen E, Duvic M, Frankel A, et al.: Pivotal phase III trial of two dose
levels of denileukin diftitox for the treatment of cutaneous T-cell
lymphoma. Journal of Clinical Oncology 19(2): 376-388, 2001.
9. Siegel RS, Pandolfino T, Guitart J, et al.: Primary cutaneous T-cell
lymphoma: review and current concepts. Journal of Clinical Oncology
18(15): 2908-2925, 2000.
10. Duvic M, Hymes K, Heald P, et al.: Bexarotene is effective and safe for
treatment of refractory advanced-stage cutaneous T-cell lymphma:
multinational phase II-III trial results. Journal of Clinical Oncology
19(9): 2456-2471, 2001.
** STAGE I MYCOSIS FUNGOIDES/SEZARY SYNDROME **
Since several forms of treatment can produce complete resolution of skin
lesions in this stage, the choice of therapy is dependent on local expertise
and the facilities available. With therapy, the survival of patients with
stage IA disease can be expected to be the same as age and gender-matched
controls.[1,2]
Standard treatment options:
1. PUVA: psoralen and ultraviolet A radiation. Therapeutic trials with PUVA
have shown a 62% to 90% complete remission rate with early cutaneous stages
achieving the best responses. Continued maintenance therapy with PUVA at more
protracted intervals is generally required to prolong remission duration.[3,4]
PUVA combined with interferon alfa-2a is associated with a high response
rate.[5]
2. TSEB: total-skin electron-beam irradiation. Electron irradiation of
appropriate energies will penetrate only to the dermis, and thus the skin alone
can be treated without systemic effects. This therapy requires considerable
technical expertise to deliver, can result in short- and long-term cutaneous
toxic effects, and is not widely available. Based on the long-term survival of
these early stage patients, electron-beam irradiation is sometimes used with
curative intent.[6-8] Long-term disease-free survival can be achieved in
patients with unilesional mycosis fungoides treated with local radiation
therapy.[9]
3. Topical mechlorethamine (nitrogen mustard). Topical application of
mechlorethamine has produced regression of cutaneous lesions, with particular
efficacy in early stages of disease. The overall complete remission rate is
related to skin stage; 50% to 80% of TNM classification T1, and 25% to 75% of
T2 patients have complete responses. Treatments are usually continued for 2 to
3 years. Continuous 5-year disease-free survival may be possible in up to one
third of T1 patients.[6,10,11]
4. Local electron-beam irradiation or orthovoltage radiation therapy may be
used to palliate areas of bulky or symptomatic skin disease.
5. Interferon alfa alone or in combination with topical therapy.[12]
6. Bexarotene, an oral or topical retinoid.[13]
References:
1. Kim YH, Jensen RA, Watanabe GL, et al.: Clinical stage IA (limited patch
and plaque) mycosis fungoides: a long-term outcome analysis. Archives
of Dermatology 132(11): 1309-1313, 1996.
2. Zackheim HS, Amin S, Kashani-Sabet M, et al.: Prognosis in cutaneous
T-cell lymphoma by skin stage: long-term survival in 489 patients.
Journal of the American Academy of Dermatology 40(3): 418-425, 1999.
3. Herrmann JJ, Roenigk HH, Hurria A, et al.: Treatment of mycosis fungoides
with photochemotherapy (PUVA): long-term follow-up. Journal of the
American Academy of Dermatology 33(2, Part 1): 234-242, 1995.
4. Ramsey DL, Lish KM, Yalowitz CB, et al.: Ultraviolet-B phototherapy for
early-stage cutaneous T-cell lymphoma. Archives of Dermatology 128(7):
931-933, 1992.
5. Kuzel TM, Roenigk HH, Samuelson E, et al.: Effectiveness of interferon
alfa-2a combined with phototherapy for mycosis fungoides and the Sezary
syndrome. Journal of Clinical Oncology 13(1): 257-263, 1995.
6. Chinn DM, Chow S, Kim YH, et al.: Total skin electron beam therapy with
or without adjuvant topical nitrogen mustard or nitrogen mustard alone
as initial treatment of T2 and T3 mycosis fungoides. International
Journal of Radiation Oncology, Biology, Physics 43(5): 951-958, 1999.
7. Hoppe RT, Cox RS, Fuks Z, et al.: Electron-beam therapy for mycosis
fungoides: the Stanford University experience. Cancer Treatment Reports
63(4): 691-700, 1979.
8. Quiros PA, Jones GW, Kacinski BM, et al.: Total skin electron beam
therapy followed by adjuvant psoralen/ultraviolet-A light in the
management of patients with T1 and T2 cutaneous T-cell lymphoma (mycosis
fungoides). International Journal of Radiation Oncology, Biology,
Physics 38(5): 1027-1035, 1997.
9. Micaily B, Miyamoto C, Kantor G, et al.: Radiotherapy for unilesional
mycosis fungoides. International Journal of Radiation Oncology,
Biology, Physics 42(2) 361-364, 1998.
10. Vonderheid EC, Tan ET, Kantor AF, et al.: Long-term efficacy, curative
potential, and carcinogenicity of topical mechlorethamine chemotherapy
in cutaneous T cell lymphoma. Journal of the American Academy of
Dermatology 20(3): 416-428, 1989.
11. Hoppe RT, Abel EA, Deneau DG, et al.: Mycosis fungoides: management with
topical nitrogen mustard. Journal of Clinical Oncology 5(11):
1796-1803, 1987.
12. Kuzel TM, Eastern Cooperative Oncology Group: Phase III Study of Topical
Therapy of Psoralen With Phototherapy (PUVA), Nitrogen Mustard
(Mechlorethamine HCL) Chemotherapy, or Total Skin Electron Beam (TSE)
Alone vs One Topical Therapy Combined With Interferon Alfa-2b for
Cutaneous T-Cell Lymphoma (CTCL) (Summary Last Modified 06/1999),
E-1495, clinical trial, closed, 04/22/1999.
13. Duvic M, Hymes K, Heald P, et al.: Bexarotene is effective and safe for
treatment of refractory advanced-stage cutaneous T-cell lymphma:
multinational phase II-III trial results. Journal of Clinical Oncology
19(9): 2456-2471, 2001.
** STAGE II MYCOSIS FUNGOIDES/SEZARY SYNDROME **
No curative therapy exists for patients with stage II disease. Therefore, the
choice of initial palliative therapy is dependent on the patient's symptoms and
the local expertise with each modality.
A randomized study compared combined total-skin electron-beam irradiation
(TSEB) plus combination chemotherapy to conservation therapy consisting of
sequential topical therapies in 103 patients. In the latter group, combination
chemotherapy was reserved for symptomatic extracutaneous disease or for disease
refractory to topical therapies. Patients of any stage were eligible.
Although the complete response rate was higher with combined therapy, toxic
effects were considerably greater and there was no difference in disease-free
or overall survival between the two groups.[1]
Standard treatment options:
1. PUVA: psoralen and ultraviolet A radiation. Therapeutic trials with PUVA
have shown a 62% to 90% complete remission rate with early cutaneous stages
achieving the best responses. Maintenance therapy with PUVA is generally
required to prolong remission duration.[2] PUVA combined with interferon
alfa-2a is associated with a high response rate.[3]
2. TSEB: total-skin electron-beam irradiation. Electron irradiation of
appropriate energies will penetrate only to to the dermis, and thus the skin
alone can be treated without systemic effects. This therapy requires a
radiation therapy facility with physics support, considerable technical
expertise, and precise dosimetry. It can provide excellent palliation with
complete response rates of up to 80%.[4-6]
3. Topical mechlorethamine (nitrogen mustard). Topical application of
mechlorethamine has produced regression of cutaneous lesions, with particular
efficacy in early stages of disease. The overall complete remission rate is
related to skin stage; 25% to 75% of TNM classification T2 and up to 50% of T3
patients have complete responses. Treatments are usually continued for 2 to 3
years.[4,7,8]
4. Local electron-beam irradiation or orthovoltage radiation therapy may also
be used to palliate areas of bulky or symptomatic disease.
5. Interferon alfa alone or in combination with topical therapy.[9,10]
6. Bexarotene, an oral or topical retinoid.[11]
References:
1. Kaye FJ, Bunn PA, Steinberg SM, et al.: A randomized trial comparing
combination electron-beam radiation and chemotherapy with topical
therapy in the initial treatment of mycosis fungoides. New England
Journal of Medicine 321(26): 1784-1790, 1989.
2. Herrmann JJ, Roenigk HH, Hurria A, et al.: Treatment of mycosis fungoides
with photochemotherapy (PUVA): long-term follow-up. Journal of the
American Academy of Dermatology 33(2, Part 1): 234-242, 1995.
3. Kuzel TM, Roenigk HH, Samuelson E, et al.: Effectiveness of interferon
alfa-2a combined with phototherapy for mycosis fungoides and the Sezary
syndrome. Journal of Clinical Oncology 13(1): 257-263, 1995.
4. Chinn DM, Chow S, Kim YH, et al.: Total skin electron beam therapy with
or without adjuvant topical nitrogen mustard or nitrogen mustard alone
as initial treatment of T2 and T3 mycosis fungoides. International
Journal of Radiation Oncology, Biology, Physics 43(5): 951-958, 1999.
5. Hoppe RT, Cox RS, Fuks Z, et al.: Electron-beam therapy for mycosis
fungoides: the Stanford University experience. Cancer Treatment Reports
63(4): 691-700, 1979.
6. Quiros PA, Jones GW, Kacinski BM, et al.: Total skin electron beam
therapy followed by adjuvant psoralen/ultraviolet-A light in the
management of patients with T1 and T2 cutaneous T-cell lymphoma (mycosis
fungoides). International Journal of Radiation Oncology, Biology,
Physics 38(5): 1027-1035, 1997.
7. Vonderheid EC, Tan ET, Kantor AF, et al.: Long-term efficacy, curative
potential, and carcinogenicity of topical mechlorethamine chemotherapy
in cutaneous T cell lymphoma. Journal of the American Academy of
Dermatology 20(3): 416-428, 1989.
8. Hoppe RT, Abel EA, Deneau DG, et al.: Mycosis fungoides: management with
topical nitrogen mustard. Journal of Clinical Oncology 5(11):
1796-1803, 1987.
9. Foss FM, Ihde DC, Breneman DL, et al.: Phase II study of pentostatin and
intermittent high-dose recombinant interferon alfa-2a in advanced
mycosis fungoides/Sezary syndrome. Journal of Clinical Oncology 10(12):
1907-1913, 1992.
10. Kuzel TM, Eastern Cooperative Oncology Group: Phase III Study of Topical
Therapy of Psoralen With Phototherapy (PUVA), Nitrogen Mustard
(Mechlorethamine HCL) Chemotherapy, or Total Skin Electron Beam (TSE)
Alone vs One Topical Therapy Combined With Interferon Alfa-2b for
Cutaneous T-Cell Lymphoma (CTCL) (Summary Last Modified 06/1999),
E-1495, clinical trial, closed, 04/22/1999.
11. Duvic M, Hymes K, Heald P, et al.: Bexarotene is effective and safe for
treatment of refractory advanced-stage cutaneous T-cell lymphma:
multinational phase II-III trial results. Journal of Clinical Oncology
19(9): 2456-2471, 2001.
** STAGE III MYCOSIS FUNGOIDES/SEZARY SYNDROME **
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
No curative treatment exists for patients with stage III disease. Therefore,
the initial choice of palliative therapy is dependent on the local expertise
with each modality. In patients with the Sezary syndrome, there is a high
probability of extracutaneous involvement, and therefore systemic chemotherapy
is often given, although there is no proof that this affects survival.
A randomized study compared combined total-skin electron-beam irradiation
(TSEB) plus combination chemotherapy to conservation therapy consisting of
sequential topical therapies in 103 patients. In the latter group, combination
chemotherapy was reserved for symptomatic extracutaneous disease or for disease
refractory to topical therapies. Patients of any stage were eligible.
Although the complete response rate was higher with combined therapy, toxic
effects were considerably greater, and there was no difference in disease-free
or overall survival between the two groups.[1][Level of evidence: 1iiA]
Standard treatment options (note that in this clinical setting, the skin is
easily injured; any of the topical therapies must be administered with extreme
caution):
1. PUVA: psoralen and ultraviolet A radiation. Therapeutic trials with PUVA
have shown a 62% to 90% complete remission rate with early cutaneous stages
achieving the best responses. It may be used in conjunction with systemic
treatment. Maintenance therapy with PUVA is generally required to prolong
remission duration.[2] PUVA combined with interferon alfa-2a is associated
with a high response rate.[3]
2. TSEB: total-skin electron-beam irradiation. Electron irradiation of
appropriate energies will penetrate only to the dermis, and thus the skin alone
can be treated without systemic effects. This therapy requires an excellent
radiation therapy facility with physics support, considerable technical
expertise, and precise dosimetry. This therapy can produce excellent
palliation with complete response rates of up to 80%.[4,5]
3. Local electron-beam irradiation or orthovoltage radiation therapy may also
be used to palliate areas of bulky or symptomatic disease.
4. Fludarabine, 2-chlorodeoxyadenosine, and pentostatin are active agents for
mycosis fungoides and Sezary syndrome.[6-9]
5. Interferon alfa alone or in combination with topical therapy.[7,10,11]
6. Denileukin diftitox (interleukin-2 fusion toxin) for CD25 and MF.[12,13]
7. Systemic chemotherapy (single agent or combination) often combined with
treatment directed at the skin.[1,14,15]
8. Extracorporeal photochemotherapy.[16,17]
9. Topical mechlorethamine (nitrogen mustard). This form of treatment may be
used palliatively or to supplement therapeutic approaches directed against
nodal or visceral disease. The overall complete remission rate of TNM
classification T4 patients is 20% to 40%. Treatments are usually continued for
2 to 3 years.[18]
10. Bexarotene, an oral or topical retinoid.[19]
References:
1. Kaye FJ, Bunn PA, Steinberg SM, et al.: A randomized trial comparing
combination electron-beam radiation and chemotherapy with topical
therapy in the initial treatment of mycosis fungoides. New England
Journal of Medicine 321(26): 1784-1790, 1989.
2. Herrmann JJ, Roenigk HH, Hurria A, et al.: Treatment of mycosis fungoides
with photochemotherapy (PUVA): long-term follow-up. Journal of the
American Academy of Dermatology 33(2, Part 1): 234-242, 1995.
3. Kuzel TM, Roenigk HH, Samuelson E, et al.: Effectiveness of interferon
alfa-2a combined with phototherapy for mycosis fungoides and the Sezary
syndrome. Journal of Clinical Oncology 13(1): 257-263, 1995.
4. Jones GW, Rosenthal D, Wilson LD: Total skin electron radiation for
patients with erythrodermic cutaneous T-cell lymphoma (mycosis fungoides
and the Sezary syndrome). Cancer 85(9): 1985-1995, 1999.
5. Reddy S, Parker CM, Shidnia H, et al.: Total skin electron beam radiation
therapy for mycosis fungoides. American Journal of Clinical Oncology
15(2): 119-124, 1992.
6. Saven A, Carrera CJ, Carson DA, et al.: 2-Chlorodeoxyadenosine: an active
agent in the treatment of cutaneous T-cell lymphoma. Blood 80(3):
587-592, 1992.
7. Foss FM, Ihde DC, Breneman DL, et al.: Phase II study of pentostatin and
intermittent high-dose recombinant interferon alfa-2a in advanced
mycosis fungoides/Sezary syndrome. Journal of Clinical Oncology 10(12):
1907-1913, 1992.
8. Foss FM, Ihde DC, Linnoila IR, et al.: Phase II trial of fludarabine
phosphate and interferon alfa-2a in advanced mycosis fungoides/Sezary
syndrome. Journal of Clinical Oncology 12(10): 2051-2059, 1994.
9. Kurzrock R, Pilat S, Duvic M: Pentostatin therapy of T-cell lymphomas
with cutaneous manifestations. Journal of Clinical Oncology 17(10):
3117-3121, 1999.
10. Kuzel TM, Eastern Cooperative Oncology Group: Phase III Study of Topical
Therapy of Psoralen With Phototherapy (PUVA), Nitrogen Mustard
(Mechlorethamine HCL) Chemotherapy, or Total Skin Electron Beam (TSE)
Alone vs One Topical Therapy Combined With Interferon Alfa-2b for
Cutaneous T-Cell Lymphoma (CTCL) (Summary Last Modified 06/1999),
E-1495, clinical trial, closed, 04/22/1999.
11. Olsen EA, Bunn PA: Interferon in the treatment of cutaneous T-cell
lymphoma. Hematology/Oncology Clinics of North America 9(5): 1089-1107,
1995.
12. Olsen E, Duvic M, Frankel A, et al.: Pivotal phase III trial of two dose
levels of denileukin diftitox for the treatment of cutaneous T-cell
lymphoma. Journal of Clinical Oncology 19(2): 376-388, 2001.
13. Siegel RS, Pandolfino T, Guitart J, et al.: Primary cutaneous T-cell
lymphoma: review and current concepts. Journal of Clinical Oncology
18(15): 2908-2925, 2000.
14. Rosen ST, Foss FM: Chemotherapy for mycosis fungoides and the Sezary
syndrome. Hematology/Oncology Clinics of North America 9(5): 1109-1116,
1995.
15. Zackheim HS, Epstein EH: Low-dose methotrexate for the Sezary syndrome.
Journal of the American Academy of Dermatology 21(4 pt 1): 757-762,
1989.
16. Edelson R, Berger C, Gasparro F, et al.: Treatment of cutaneous T-cell
lymphoma by extracorporeal photochemotherapy. New England Journal of
Medicine 316(6): 297-303, 1987.
17. Heald PW, Perez MI, McKiernan G, et al.: Extracorporeal photochemotherapy
for CTCL. Progress in Clinical and Biological Research 337: 443-447,
1990.
18. Vonderheid EC, Tan ET, Kantor AF, et al.: Long-term efficacy, curative
potential, and carcinogenicity of topical mechlorethamine chemotherapy
in cutaneous T cell lymphoma. Journal of the American Academy of
Dermatology 20(3): 416-428, 1989.
19. Duvic M, Hymes K, Heald P, et al.: Bexarotene is effective and safe for
treatment of refractory advanced-stage cutaneous T-cell lymphma:
multinational phase II-III trial results. Journal of Clinical Oncology
19(9): 2456-2471, 2001.
** STAGE IV MYCOSIS FUNGOIDES/SEZARY SYNDROME **
The use of single alkylating agents has produced objective responses in 60% of
patients with a duration of less than 6 months. One of the alkylating agents
(mechlorethamine, cyclophosphamide, or chlorambucil), or the antimetabolite
methotrexate is the most frequently used. Single agents have not been shown to
cure any patients, and insufficient data exist to determine whether these
agents prolong survival. Combination chemotherapy is not definitely superior
to single agents. Even in stage IV disease, treatments directed at the skin
may provide significant palliation.
A randomized study compared combined total-skin electron-beam irradiation
(TSEB) plus combination chemotherapy to conservation therapy consisting of
sequential topical therapies in 103 patients. In the latter group, combination
chemotherapy was reserved for symptomatic extracutaneous disease or for disease
refractory to topical therapies. Patients of any stage were eligible.
Although the complete response rate was higher with combined therapy, toxic
effects were considerably greater and there was no difference in disease-free
or overall survival between the two groups.[1]
Standard treatment options:
1. PUVA: psoralen and ultraviolet A radiation. Therapeutic trials with PUVA
have shown a 62% to 90% complete remission rate with early cutaneous stages
achieving the best responses. It may be used in conjunction with systemic
treatment. Maintenance therapy with PUVA is generally required to prolong
remission duration.[2] PUVA combined with interferon alfa-2a is associated
with a high response rate.[3]
2. TSEB: total-skin electron-beam irradiation. Electron irradiation of
appropriate energies will penetrate only to the dermis, and thus the skin alone
can be treated without systemic effects. This therapy requires an excellent
radiation therapy facility with physics support, considerable technical
expertise, and precise dosimetry. This therapy can produce excellent
palliation and may be combined with systemic treatment.[4]
3. Local electron-beam irradiation or orthovoltage radiation therapy may also
be used to palliate areas of bulky or symptomatic disease.
4. Fludarabine, 2-chlorodeoxyadenosine, and pentostatin are active agents for
mycosis fungoides and Sezary syndrome.[5-7]
5. Interferon alfa alone or in combination with topical therapy.[6,8,9]
6. Denileukin diftitox (interleukin-2 fusion toxin) for CD25 and MF.[10,11]
7. Systemic chemotherapy: chlorambucil + prednisone, mechlorethamine,
cyclophosphamide, methotrexate, combination chemotherapy [1,12,13]
8. Topical mechlorethamine (nitrogen mustard). This form of treatment may be
used palliatively or to supplement therapeutic approaches directed against
nodal or visceral disease. The overall complete remission rate in 243 patients
was 64% and was related to stage; up to 35% of stage IV patients had complete
responses. Treatments are usually continued for 2 to 3 years.[14]
9. Extracorporeal photochemotherapy alone[15-17] or in combination with
TSEB.[18]
10. Serotherapy with monoclonal antibodies.[19,20]
11. Bexarotene, an oral or topical retinoid.[21]
References:
1. Kaye FJ, Bunn PA, Steinberg SM, et al.: A randomized trial comparing
combination electron-beam radiation and chemotherapy with topical
therapy in the initial treatment of mycosis fungoides. New England
Journal of Medicine 321(26): 1784-1790, 1989.
2. Herrmann JJ, Roenigk HH, Hurria A, et al.: Treatment of mycosis fungoides
with photochemotherapy (PUVA): long-term follow-up. Journal of the
American Academy of Dermatology 33(2, Part 1): 234-242, 1995.
3. Kuzel TM, Roenigk HH, Samuelson E, et al.: Effectiveness of interferon
alfa-2a combined with phototherapy for mycosis fungoides and the Sezary
syndrome. Journal of Clinical Oncology 13(1): 257-263, 1995.
4. Jones GW, Rosenthal D, Wilson LD: Total skin electron radiation for
patients with erythrodermic cutaneous T-cell lymphoma (mycosis fungoides
and the Sezary syndrome). Cancer 85(9): 1985-1995, 1999.
5. Saven A, Carrera CJ, Carson DA, et al.: 2-Chlorodeoxyadenosine: an active
agent in the treatment of cutaneous T-cell lymphoma. Blood 80(3):
587-592, 1992.
6. Foss FM, Ihde DC, Breneman DL, et al.: Phase II study of pentostatin and
intermittent high-dose recombinant interferon alfa-2a in advanced
mycosis fungoides/Sezary syndrome. Journal of Clinical Oncology 10(12):
1907-1913, 1992.
7. Foss FM, Ihde DC, Linnoila IR, et al.: Phase II trial of fludarabine
phosphate and interferon alfa-2a in advanced mycosis fungoides/Sezary
syndrome. Journal of Clinical Oncology 12(10): 2051-2059, 1994.
8. Olsen EA, Bunn PA: Interferon in the treatment of cutaneous T-cell
lymphoma. Hematology/Oncology Clinics of North America 9(5): 1089-1107,
1995.
9. Kuzel TM, Eastern Cooperative Oncology Group: Phase III Study of Topical
Therapy of Psoralen With Phototherapy (PUVA), Nitrogen Mustard
(Mechlorethamine HCL) Chemotherapy, or Total Skin Electron Beam (TSE)
Alone vs One Topical Therapy Combined With Interferon Alfa-2b for
Cutaneous T-Cell Lymphoma (CTCL) (Summary Last Modified 06/1999),
E-1495, clinical trial, closed, 04/22/1999.
10. Olsen E, Duvic M, Frankel A, et al.: Pivotal phase III trial of two dose
levels of denileukin diftitox for the treatment of cutaneous T-cell
lymphoma. Journal of Clinical Oncology 19(2): 376-388, 2001.
11. Siegel RS, Pandolfino T, Guitart J, et al.: Primary cutaneous T-cell
lymphoma: review and current concepts. Journal of Clinical Oncology
18(15): 2908-2925, 2000.
12. Rosen ST, Foss FM: Chemotherapy for mycosis fungoides and the Sezary
syndrome. Hematology/Oncology Clinics of North America 9(5): 1109-1116,
1995.
13. Zackheim HS, Epstein EH: Low-dose methotrexate for the Sezary syndrome.
Journal of the American Academy of Dermatology 21(4 pt 1): 757-762,
1989.
14. Vonderheid EC, Tan ET, Kantor AF, et al.: Long-term efficacy, curative
potential, and carcinogenicity of topical mechlorethamine chemotherapy
in cutaneous T cell lymphoma. Journal of the American Academy of
Dermatology 20(3): 416-428, 1989.
15. Edelson R, Berger C, Gasparro F, et al.: Treatment of cutaneous T-cell
lymphoma by extracorporeal photochemotherapy. New England Journal of
Medicine 316(6): 297-303, 1987.
16. Heald PW, Perez MI, McKiernan G, et al.: Extracorporeal photochemotherapy
for CTCL. Progress in Clinical and Biological Research 337: 443-447,
1990.
17. Fraser-Andrews E, Seed P, Whittaker S, et al.: Extracorporeal
photopheresis in Sezary syndrome: no significant effect in the survival
of 44 patients with a peripheral blood T-cell clone. Archives of
Dermatology 134(8): 1001-1005, 1998.
18. Wilson LD, Jones GW, Kim D, et al.: Experience with total skin electron
beam therapy in combination with extracorporeal photopheresis in the
management of patients with erythrodermic (T4) mycosis fungoides.
Journal of the American Academy of Dermatology 43(1 pt 1): 54-60, 2000.
19. Knox SJ, Levy R, Hodgkinson S, et al.: Observations on the effect of
chimeric anti-CD4 monoclonal antibody in patients with mycosis
fungoides. Blood 77(1): 20-30, 1991.
20. Rosen ST, Zimmer AM, Goldman-Leikin R, et al.: Radioimmunodetection and
radioimmunotherapy of cutaneous T cell lymphomas using an 131I-labeled
monoclonal antibody: an Illinois Cancer Council study. Journal of
Clinical Oncology 5(4): 562-573, 1987.
21. Duvic M, Hymes K, Heald P, et al.: Bexarotene is effective and safe for
treatment of refractory advanced-stage cutaneous T-cell lymphma:
multinational phase II-III trial results. Journal of Clinical Oncology
19(9): 2456-2471, 2001.
** RECURRENT MYCOSIS FUNGOIDES/SEZARY SYNDROME **
The treatment of relapsed patients with cutaneous T-cell lymphomas (CTCL)
involves the joint decisions of the dermatologist, medical oncologist, and
radiation oncologist. It may be possible to re-treat localized areas of
relapse with additional electron-beam irradiation or possibly to repeat total-
skin electron-beam irradiation therapy.[1] Photon irradiation to bulky skin or
nodal masses may prove beneficial. If these options are not possible, then
continued topical treatment with other modalities such as mechlorethamine or
psoralen and ultraviolet A radiation (PUVA) may be warranted to relieve
cutaneous symptoms.
Clinical trials, if possible, should be considered as the next therapeutic
option. PUVA combined with interferon alfa-2a is associated with a high
response rate.[2] Extracorporeal photochemotherapy has produced tumor
regression in patients resistant to other therapies.[3,4] Radioimmunotherapy
using a 131I-labeled monoclonal antibody directed against a T-cell antigen has
produced brief responses in a clinical trial.[5] Fludarabine,
2-chlorodeoxyadenosine, and pentostatin are active agents for mycosis fungoides
and Sezary syndrome.[6-8] The interleukin-2 fusion toxin, denileukin diftitox,
is given monthly with response rates of about 30% to 40% for patients with CD25
and MF.[9] Bexarotene is a retinoid available in an oral or topical form with
activity in patients with recurrent MF.[10,11] New PNP inhibitors such as
peldesine are under clinical evaluation.[12] Allogeneic or autologous bone
marrow transplantation is also under clinical evaluation.
References:
1. Becker M, Hoppe RT, Knox SJ: Multiple courses of high-dose total skin
electron beam therapy in the management of mycosis fungoides.
International Journal of Radiation Oncology, Biology, Physics 32(5):
1445-1449, 1995.
2. Kuzel TM, Roenigk HH, Samuelson E, et al.: Effectiveness of interferon
alfa-2a combined with phototherapy for mycosis fungoides and the Sezary
syndrome. Journal of Clinical Oncology 13(1): 257-263, 1995.
3. Edelson R, Berger C, Gasparro F, et al.: Treatment of cutaneous T-cell
lymphoma by extracorporeal photochemotherapy. New England Journal of
Medicine 316(6): 297-303, 1987.
4. Heald PW, Perez MI, McKiernan G, et al.: Extracorporeal photochemotherapy
for CTCL. Progress in Clinical and Biological Research 337: 443-447,
1990.
5. Rosen ST, Zimmer AM, Goldman-Leikin R, et al.: Radioimmunodetection and
radioimmunotherapy of cutaneous T cell lymphomas using an 131I-labeled
monoclonal antibody: an Illinois Cancer Council study. Journal of
Clinical Oncology 5(4): 562-573, 1987.
6. Saven A, Carrera CJ, Carson DA, et al.: 2-Chlorodeoxyadenosine: an active
agent in the treatment of cutaneous T-cell lymphoma. Blood 80(3):
587-592, 1992.
7. Foss FM, Ihde DC, Breneman DL, et al.: Phase II study of pentostatin and
intermittent high-dose recombinant interferon alfa-2a in advanced
mycosis fungoides/Sezary syndrome. Journal of Clinical Oncology 10(12):
1907-1913, 1992.
8. Foss FM, Ihde DC, Linnoila IR, et al.: Phase II trial of fludarabine
phosphate and interferon alfa-2a in advanced mycosis fungoides/Sezary
syndrome. Journal of Clinical Oncology 12(10): 2051-2059, 1994.
9. Olsen E, Duvic M, Frankel A, et al.: Pivotal phase III trial of two dose
levels of denileukin diftitox for the treatment of cutaneous T-cell
lymphoma. Journal of Clinical Oncology 19(2): 376-388, 2001.
10. Miller VA, Benedetti FM, Rigas JR, et al.: Initial clinical trial of
selective retinoid X receptor ligand, LGD1069. Journal of Clinical
Oncology 15(2): 790-795, 1997.
11. Duvic M, Hymes K, Heald P, et al.: Bexarotene is effective and safe for
treatment of refractory advanced-stage cutaneous T-cell lymphma:
multinational phase II-III trial results. Journal of Clinical Oncology
19(9): 2456-2471, 2001.
12. Bantia S, Montgomery JA, Johnson HG, et al.: In vivo and in vitro
pharmacologic activity of the purine nucleoside phosphorylase inhibitor
BCX-34: the role of GTP and dGTP. Immunopharmacology 35(1): 53-63,
1996.
Date Last Modified: 01/2002
******************************************************************************
* This information from PDQ is reviewed regularly by members of the PDQ *
* Editorial Boards. If you have specific comments on the content of this *
* information, direct them to: PDQ Editorial Board, CIPS/NCI, 6116 *
* Executive Boulevard, Suite 3002B, MSC-8321, 20892-8321, fax: 301-480-8105.*
* *
* The PDQ database also contains listings of clinical trial protocols and *
* directories of organizations and physicians who treat cancer patients, *
* but this information is not available through CancerMail. For more *
* information on accessing PDQ, consult the CancerMail Contents List. *
******************************************************************************
|
[Home] | [Search] | [Medical Q&A Forums] | [Patient Network] |
This information has been brought to you by
Med Help International,
licenced by the National Cancer Institute as a distributor of CancerNet.