levoleucovorin and Mycosis-Fungoides

Malignant lymphoma of the skin is a type of extranodal lymphoma with a benign prognosis, in which the main organ involved is the skin. Some 80-90% of the cases in Japan show a T-cell phenotype. Mycosis fungoides and Sézary syndrome are common T-cell lymphomas of the skin. The tumor cells of mycosis fungoides, small and medium-sized cells with cerebriform nuclei, are detected in an epidermo-dermo junction. The tumor cells show CD3, CD4 and CLA, (cutaneous lymphocyte associated antigen) positivity. Various forms of topical therapy, such as topical steroid, photochemotherapy (PUVA), and interferons, have been indicated for the good-risk group (stages I A, I B and II A). Electron-beam irradiation, various chemotherapy, such as low-dose etoposide, low-dose MTX and CPT-11 and deoxy coformycin (DCF) plus IFNs, have been indicated for intermediate-risk group (stage II B, III and IV A). BRMs plus low-dose etoposide, electron-beam irradiation and a multiagent combination chemotherapy, such as MACOP-B, M-BACOD or ProMACE-CytaBOM, have been indicated for the high-risk group (stages IV A and IV B). Cutaneous B cell lymphoma (CBCL) can be diagnosed using a molecular biological assay. The tumor cells of CBCL do not express T-cell antigens such as CD2, CD3 and CD43 and show B-cell antigens such as sIg, CD19, CD20 and CD22. Electron-beam irradiation has been indicated for early-stage CBCL (stages I and II). An effective multiagent combination chemotherapy, such as MACOP-B, M-BACOD or ProMACE-CytaBOM, is required for patients with advanced stage CBCL (stages III and IV).

Topics: Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bleomycin; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Electrons; Etoposide; Humans; Interferon-gamma; Leucovorin; Membrane Glycoproteins; Methotrexate; Mycosis Fungoides; Prednisone; PUVA Therapy; Skin Neoplasms; Vincristine

Radiation therapy has a broad range of applications in the management of patients with non-Hodgkin's lymphoma. It has curative potential for patients with Stage I to II low-grade lymphoma (small lymphocytic, follicular small cleaved, and follicular mixed) and has substantial palliative efficacy in patients with more advanced stage low-grade lymphoma. Low-dose whole-body irradiation may be used as palliative therapy even in patients with bone marrow involvement by these lymphomas. In the management of the large cell lymphomas (diffuse large cell, diffuse mixed, and immunoblastic), radiation alone has curative potential in only the most favorable early-stage presentations. However, since radiation can achieve significant responses in these tumors, it should be considered for inclusion in combined-modality programs. Reports that have appeared in the literature as well as results of treatment at Stanford that bear upon these issues are reviewed.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Dexamethasone; Doxorubicin; Follow-Up Studies; Humans; Leucovorin; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Meningeal Neoplasms; Methotrexate; Mycosis Fungoides; Palliative Care; Prednisone; Radiotherapy Dosage; Skin Neoplasms; Time Factors; Vincristine; Whole-Body Irradiation

The treatment of advanced mycosis fungoides is a therapeutic challenge. A variety of treatment approaches have been used. In our experience, chemotherapy has been most useful. The purpose of this study was to evaluate the effectiveness of the synergy previously demonstrated between methotrexate and fluorouracil in the treatment of advanced mycosis fungoides. Ten patients with mycosis fungoides and Sézary syndrome stages IIa (n = 1), II-b (n = 4), III (n = 1), IVa (n = 2), and IVb (n = 2) were treated with sequential methotrexate followed by fluorouracil and leucovorin rescue. Each patient received several courses of chemotherapy at varying intervals, as required for control of their disease.. The duration of treatment ranged from 3 to 78 months, with an average duration of 33 months. The number of cycles of chemotherapy administered to each patient ranged from five to 45, with an average of 18 infusions per patient. The average survival in patients with tumors was 5.25 years, with a median survival of 6 years. Eight of 10 patients achieved at least 80% clearing and the remaining two achieved at least 60% clearing. Adverse reactions were minimal and included nausea and vomiting, mucositis, and leukopenia in only one patient.. Sequential methotrexate and fluorouracil chemotherapy is an effective and safe treatment for advanced mycosis fungoides and Sézary syndrome. This regimen is extremely well tolerated, with minimal toxic side effects.

Topics: Adult; Aged; Aged, 80 and over; Algorithms; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Humans; Infusions, Intravenous; Leucovorin; Methotrexate; Middle Aged; Mycosis Fungoides; Neoplasm Staging; Neoplasms, Multiple Primary; Sezary Syndrome; Skin Neoplasms; Survival Rate

Radiation therapy has a broad range of applications in the management of patients with non-Hodgkin's lymphoma. It has curative potential for patients with Stage I to II low-grade lymphoma (small lymphocytic, follicular small cleaved, and follicular mixed) and has substantial palliative efficacy in patients with more advanced stage low-grade lymphoma. Low-dose whole-body irradiation may be used as palliative therapy even in patients with bone marrow involvement by these lymphomas. In the management of the large cell lymphomas (diffuse large cell, diffuse mixed, and immunoblastic), radiation alone has curative potential in only the most favorable early-stage presentations. However, since radiation can achieve significant responses in these tumors, it should be considered for inclusion in combined-modality programs. Reports that have appeared in the literature as well as results of treatment at Stanford that bear upon these issues are reviewed.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Dexamethasone; Doxorubicin; Follow-Up Studies; Humans; Leucovorin; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Meningeal Neoplasms; Methotrexate; Mycosis Fungoides; Palliative Care; Prednisone; Radiotherapy Dosage; Skin Neoplasms; Time Factors; Vincristine; Whole-Body Irradiation

Balancing efficacy and safety of drugs is key for successful cancer therapy, as adverse reactions can prohibit the use of efficacious treatments. Pralatrexate (PDX) is a novel antifolate with a higher affinity for tumor cells than methotrexate, Food and Drug Administration (FDA) approved for use in relapsed and refractory peripheral T-cell lymphoma (PTCL) and transformed mycosis fungoides (T-MF). Patients with T-MF have a higher incidence of adverse events than patients with other lymphomas, necessitating a lower recommended dose of 15 mg/m(2) (vs. 30 mg/m(2) for PTCL). Dose-limiting toxicity (DLT) mucositis occurs in about 25% of patients with T-MF, but milder mucositis is observed in almost all patients with T-MF, frequently leading to therapy discontinuation despite clinical response. Leucovorin rescue is the standard of care for high-dose methotrexate therapy, but has not been studied or recommended for use with PDX. We report our clinical experience using leucovorin with PDX (30 mg/m(2)) with good clinical response and no DLTs. Prophylactic leucovorin deserves further investigation in prospective clinical trials to allow patients with cutaneous lymphomas to receive the full benefit of PDX therapy without intolerable toxicity.

Topics: Adult; Aged; Aged, 80 and over; Aminopterin; Female; Folic Acid Antagonists; Humans; Leucovorin; Lymph Nodes; Lymphoma, T-Cell, Peripheral; Male; Mycosis Fungoides; Premedication; Skin; Tomography, X-Ray Computed

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cell Transformation, Neoplastic; Cyclophosphamide; Diabetes Mellitus; Doxorubicin; Humans; Hypertriglyceridemia; Insulin Resistance; Leucovorin; Lipodystrophy; Magnetic Resonance Imaging; Male; Methotrexate; Middle Aged; Mycosis Fungoides; Parotid Diseases; Parotid Gland; Prednisone; Skin Neoplasms; Vincristine

Biopsy specimens from a 21-year-old man showed mycosis fungoides involving the skin and lungs. Usually such a case represents a fulminant and fatal course of the disease. This patient had a complete remission of his pulmonary disease following sequential therapy with cyclophosphamide, vincristine sulfate, methotrexate, leucovorin calcium, and cytarabine (COMLA).

Topics: Adult; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Humans; Leucovorin; Lung Neoplasms; Male; Methotrexate; Mycosis Fungoides; Remission, Spontaneous; Skin Neoplasms; Vincristine

Eleven patients with stage II or III mycosis fungoides lymphoma were treated with a regimen consisting of iv infusions of methotrexate (MTX) (60-240 mg/m2) administered sequentially and oral citrovorum factor. All 11 patients experienced a good to excellent response. Complete remissions were induced in seven of the 11 patients. In most cases remissions were sustained with weekly administration of low-dose (25--50 mg) MTX. Adverse drug reactions, such as leukopenia, anemia, and mucositis, were minimal in degree. Some unique adverse reactions included skin ulcerations (three patients), a leukocytoclastic angiitis (one patient), and painful hands and feet during MTX infusions (two patients). Our experience with this regimen has led us to conclude that it is safe and very effective in the treatment of stages II and III of mycosis fungoides.

Topics: Administration, Oral; Adult; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Infusions, Parenteral; Leucovorin; Male; Methotrexate; Middle Aged; Mycosis Fungoides

Topics: Aza Compounds; Cyclophosphamide; Dermatology; Drug Therapy, Combination; Humans; Immunotherapy; Leucovorin; Methotrexate; Mycosis Fungoides; National Institutes of Health (U.S.); Statistics as Topic; United States; Uridine