Chemotherapy of malignant melanoma--current status

Curative treatment modalities for patients with malignant melanoma (MM) in advanced stages are limited. Temporary successes with chemotherapy have so far mainly been achieved after removal of all accessible tumor masses. Extensive experience with cytostatic measures has been gained over more than two decades both with therapeutic and with adjuvant schedules. Dacarbazine (DTIC), which is associated with a remission rate of approximately 20%, continues to be the most effective cytostatic drug in the treatment of MM. Systemic (poly) chemotherapeutic schedules with and without DTIC have improved the response rates in metastasizing MM in numerous phase II trials. However, these results have not been confirmed in randomized studies comparing these schedules with DTIC monochemotherapy. For the BOLD schedule (bleomycin, Oncovin, lomustine, dacarbazine), the BELD schedule (Eldisine instead of Oncovin), and the DVP combination (dacarbazine, vindesine, Platinex), initial response rates of 40-49% have been reported. However, lower response rates were recently described (DVP: 24%; BOLD: 22% and 4%). Therefore, there is still no definite evidence that polychemotherapy is superior to DTIC monotherapy in MM. In our opinion, expected response rates of 20-30% justify the use of chemotherapy in disseminated MM; in cases of further progression, therapy should be interrupted early - after 2-3 cycles. Systemic (poly) chemotherapy of metastasizing MM is indicated in patients whose general condition is good, mainly in those who have skin, soft tissue, or lung metastases. These metastases usually respond well to cytostatic treatment. In future, the combined use of cytostatics together with new antitumour molecules may reduce the general toxicity and improve the efficacy of systemic cytostatic therapy in MM. The benefits of adjuvant chemotherapy in the treatment of MM have still to be confirmed definitively. While adjuvant therapy with DTIC has proved to be ineffective in stage I, irrespective of the tumor thickness, some studies suggest that adjuvant therapy with DTIC, or combinations including DTIC, may improve the prognosis of patients in clinical stage II.     

Remission of extensive intrahepatic metastasis by C‐arm computed tomography guided chemoembolization in uveal melanoma

As soon as uveal melanoma has metastasized to the liver, response rates to systemic chemotherapy are low. It can be improved by development of special locoregional procedures. A 24‐year‐old woman suffered from inoperable hepatic metastases which grew to life‐endangering size despite both systemic chemotherapy with gemc‐itabine/treosulfan and conventional intrahepatic chemoembolization with fotemustine and starch particles. We subsequently performed two angiographic C‐arm CT‐guided, superselective chemoembolizations of the hepatic arteries feeding the tumor, using cisplatin, starch microspheres and ethiodized oil. Following this treatment, no vital tumor tissue was detectable by MRI. This remission lasted for more than 6 months and the patient's quality of life was good. A subsequent local relapse could not be treated with chemoembolization because of thrombosis of the portal vein due to tumor compression. And the patient died 20 months after first detection of metastases. However, the selective angiographic C‐arm CT‐guided chemoembolization resulted in prolongation of life with good quality despite the advanced stage of the disease.     

Transient complete remission of metastasized Merkel cell carcinoma by high-dose polychemotherapy and autologous peripheral blood stem cell transplantation

Merkel cell carcinoma (MCC) is a rare cutaneous tumour with neuroendocrine differentiation. Metastasis occurs preferentially to regional lymph nodes but distant and multiple visceral metastases may occur. Chemotherapy has been performed with a variety of protocols based largely on agents active in small-cell lung cancer. Owing to the rarity of MCC, there is no standard protocol for the treatment of metastatic disease. We report a 59-year-old patient with systemic metastatic MCC. After diagnosis of distant metastases, first-line polychemotherapy (cisplatin 80 mg m(-2), doxorubicin 50 mg m(-2), etoposide 300 mg m(-2) and bleomycin 30 mg) was administered four times at 3-weekly intervals and resulted in partial remission of metastases. Subsequently, high-dose chemotherapy according to the PEI regimen (ifosfamide 12 g m(-2), carboplatin 900 mg m(-2) and etoposide 1500 mg m(-2)) was applied, followed by autologous blood stem cell transplantation (ABSCT). This protocol resulted in a complete remission that lasted for 6 months. This is the first report on a complete remission of metastatic MCC after high-dose polychemotherapy and ABSCT. High-dose chemotherapy might be a therapeutic option in chemosensitive metastatic MCC, and further evaluation is warranted.     

Progress of multiple cutaneous and subcutaneous melanoma metastases of the face during imiquimod treatment

A 68‐year‐old man developed a local recurrence with multiple cutaneous and subcutaneous nodules three months after excision of a primary malignant melanoma of the temple. Despite extensive surgery and adjuvant irradiation, another local recurrence occurred. Following further local progression during dacarbazine chemotherapy, topical treatment with imiquimod was begun and the chemotherapy was changed to fotemustine. During this treatment further local progression occurred and two months later regional lymph node and distant metastasis were detected. The patient died from his tumor disease eighteen months after the first diagnosis of malignant melanoma.     

The treatment and prognosis of dermatomyositis: an updated review

Dermatomyositis (DM) is an idiopathic inflammatory myopathy. The mainstay of treatment for DM is oral corticosteroids. However, the dose and length of treatment is debated. Adding to the confusion, there have been no randomized controlled studies comparing the use of various corticosteroid doses and taper rates, and no controlled long-term studies assessing the hypothesis that, unlike systemic lupus erythematous, patients with DM can often achieve long-term remission off therapy. This literature review supports an approach that prednisone should be started at about 1 mg/kg/d, which is then tapered slowly based on the response. As patients respond differently to prednisone, additional therapies may be necessary. When to initiate these therapies requires clinical judgment. In addition, as we learn more about the pathophysiology of DM, newer medications that target specific mechanisms in the immune response may help us better treat the disease. Evidence-based data with long-term follow-up will allow for selection of the best treatment to maximize long-term remission, not simply short-term lowering of the systemic corticosteroid dose.     

Efficacy of superficial and deep regional hyperthermia combined with systemic chemotherapy and radiotherapy in metastatic melanoma

Background and Objective: Response rates of cutaneous‐subcutaneous or lymph node metastases of melanoma to systemic chemotherapy are rather low. We report our clinical experience with superficial and deep regional hyperthermia in combination with radiotherapy and/or chemotherapy with carboplatin. Patients/Methods: We treated 15 patients with metastatic melanoma (6 men, 9 women; age 39 – 84 years, mean age 60 years) by using superficial or deep regional hyperthermia produced by electromagnetic energy. Superficial hyperthermia was delivered to skin or lymph node metastases in combination with radiochemotherapy in 12 patients, while deep regional hyperthermia was administered with an annular array applicator to lymph node metastases either in combination with radiochemotherapy (1 patient) or with carboplatin alone (2 patients). The clinical response was assessed by clinical evaluation and/or computer tomography and/or ultrasonography at monthly intervals. Results. Both superficial and deep regional hyperthermia was well tolerated. We observed 5 complete local remissions (34 %), 6 partial local remissions (40 %) and 2 patients with stable disease (13 %). The best results were obtained in cutaneous or retroperitoneal metastases. Conclusions. Local response can be achieved in inoperable metastatic melanoma using superficial or deep regional hyperthermia in combination with radiochemotherapy or chemotherapy.     

Randomized controlled study of electrochemotherapy in the local treatment of skin metastases of melanoma

BACKGROUND: Electrochemotherapy (ECT) combines intralesional injections of bleomycin with electroporation (EP), which permeabilizes tumor cells and thus increases the bleomycin efficacy at the tumor site. OBJECTIVE: To assess whether EP therapy improves the local control of skin metastases of melanoma by intralesional bleomycin. The secondary objective was to evaluate tolerance of the treatments. PATIENTS: Patients with at least two measurable skin metastases of melanoma that were previously untreated, either in stage III with in-transit melanoma skin metastases or stage IV with no efficacy of systemic chemotherapy on these metastases. DESIGN: A prospective internally controlled study with randomization of melanoma skin metastases in each individual to intralesional injections of bleomycin alone or to intralesional injections of bleomycin with EP. The primary end point was the rate of complete local response per treated melanoma skin metastasis at week 12, and the secondary end point was tolerance. RESULTS: Fifty-four melanoma skin metastases were treated in 12 patients (8 stage IV patients under chemotherapy and 4 stage III patients free of other treatment). A local complete response was obtained in 36% (11 of 30) of melanoma skin metastases treated with bleomycin + EP and only in 8% (2 of 24) of melanoma skin metastases treated with bleomycin alone (p = .016). In the per protocol population, complete response was obtained in 74% (17 of 23) and 13% (2 of 15) of the lesions treated, respectively (p = .017). All patients (12 of 12) reported discomfort during the EP procedure, including local pain for 9 patients (75%) at the treatment site and muscle spasm with myoclonia in 3 cases (25%). No clinical or biologic systemic toxicity was noticed. CONCLUSIONS: EP increases the effect of intralesional bleomycin and improves the rate of local control in melanoma skin metastases without inducing a more systemic effect. This local treatment could be useful in a palliative strategy in patients with melanoma skin metastases.     

Therapie des metastasierten malignen Uveamelanoms

The uvea is the most common site for extra-cutaneous melanoma and uveal melanoma is the most frequent primary intraocular tumour in adults. Because its different location, biology, histology, genetic features and prognosis in comparison to cutaneous melanoma, this tumour is considered as a distinct entity in the group of malignant melanoma. While primary uveal melanoma is usually treated by ophthalmologic oncologists, metastatic diseases is often managed by dermatologic oncologists. Hematogenous spread predominantly involves the liver and is often restricted to this organ for a long period. Metastatic uveal melanoma is usually resistant to chemotherapeutic regimens established for the therapy of cutaneous melanoma. Newer therapeutic modalities, such as local intra-arterial chemotherapy into the hepatic artery, perhaps combined with embolisation of feeder blood vessels of liver metastases, improves the prognosis of metastatic uveal melanoma. Currently the nitrosourea derivate fotemustine is the drug of choice in the local hepatic and systemic treatment and seems to be superior to other chemotherapeutic agents. Following the characterisation of primary uveal melanoma, we summarize the results of different treatment protocols for metastatic disease and give an overview of new strategies.     

Duration of remission of psoriasis therapies.

The armamentarium of therapies for psoriasis continues to expand with drugs such as tazarotene, calcipotriene, and acitretin approved in recent years. New forms of old treatments such as cyclosporine and anthralin have also been introduced. Frequently, inadequate attention is devoted to duration of remission. The purpose of this article is to examine the duration of remission reported with many therapies currently used for psoriasis. Studies examining duration of remission are included. Among our conclusions were the following: the definitions of remission/relapse used in various studies differ, duration of remission is influenced by the natural history of each patient's disease, among topical monotherapies anthralin and tazarotene appear to induce longer remissions than calcipotriene and corticosteroids, among systemic agents longer remissions occur with etretinate than cyclosporine or methotrexate but compared with the remission rate of phototherapeutic modalities, especially Goeckerman and PUVA therapy, the remission rates are much less.     

Response of subcutaneous and cutaneous metastases of malignant melanoma to combined cytostatic plus interferon therapy

Summary A chemotherapy regimen consisting of dacarbazine (DTIC), vincristine, bleomycin and lomustine (CCNU) was combined with natural leucocyte interferon (IFN) in the treatment of 37 patients with cutaneous and subcutaneous metastases of malignant melanoma. Twenty-five also had concomitant lymph node, visceral, bone or brain metastases. Fifteen patients (41%) experienced complete response (CR) and 10 (27%) partial response (PR) of the superficial lesions. In addition, three patients were rendered surgically tumour-free after PR or disease stabilization during drug therapy. The median overall duration of response was 10.2 months (range 1–53 months). In disseminated disease, the combined therapy produced favourable results, particularly with regard to superficial lesions. It is also possible that this therapy may retard the growth of aggressive subcutaneous metastases in patients who have previously had multiple surgical procedures in an attempt to stabilize their disease. In a small proportion of patients, the long-term complete remission with the drug therapy alone, or in combination with surgery, suggests that this regimen might have been curative.     

Intravascular metastatic melanoma of the vena saphena magna

BACKGROUND: Melanoma blood vessel metastases are very uncommon. We report the first recorded case of intravascular metastatic melanoma of the vena saphena magna. CASE REPORT: A 74-year-old woman presented with a swelling of the upper third of her left thigh and was suspected of superficial thrombophlebitis. Two intravascular black masses were excised in the vena saphena magna. Histopathologic examination showed an endovascular metastatic melanoma positively staining for HMB45 and S-100 proteins. Acral-lentiginous melanoma of her big toe was then found. Subcutaneous lymph node and chest metastases were discovered and treatment with dacarbazine was initiated, followed by treatment with fotemustine. The patient died 21 months after the diagnosis was made. CONCLUSIONS: Only a few cases of blood vessel metastatic melanoma have been reported. We here report the first recorded case, to our knowledge, of intravascular metastatic melanoma of the vena saphena magna. Surgical exploration allowed rapid diagnosis, and histological examination confirmed the intravascular nature of a hematogenous melanoma metastasis. This case clearly illustrates the need for histologic examination of any thrombotic material.     

Mycosis fungoides and Sezary syndrome: therapeutic approach and outcome in 113 patients

BACKGROUND: Mycosis fungoides (MF) and Sezary syndrome (SS) are the most common forms of cutaneous T-cell lymphoma (CTCL). Various topical and systemic therapeutic alternatives are available, but there is no standard or definite curative treatment regimen. When making a decision about the appropriate treatment modality, the age and compliance of the patient, stage of the disease, treatment accessibility, and previous treatment history should be considered. AIM: To determine the therapeutic response of patients with MF and SS to different treatment modalities. Patients were evaluated with respect to their clinical and demographic features. METHODS: One hundred and thirteen patients diagnosed clinically and dermatopathologically with MF and SS between March 1984 and June 2001 were included in the study. RESULTS: Of the 113 patients studied, 110 had a diagnosis of MF and three had a diagnosis of SS; 101 patients (89.4%) were diagnosed with early stage (IA, IB, IIA) and 12 (10.6%) with late stage (IIB, III, IVA, IVB) disease. The age at diagnosis varied between 12 and 81 years (mean, 45.6+/-15.8 years). Fifty-five (48.7%) patients were male and 58 (51.3%) were female. The duration of the skin lesions varied between 1.5 months and 32 years (mean, 6.1 years). Psoralen plus UVA (PUVA) was the most commonly used initial treatment modality in early stage disease (91%), with a complete remission (CR) rate of 80.4%. With PUVA+interferon-alpha (INF-alpha) treatment, CR was 57% in the early stages and 33.3% in the late stages. For late stage disease, systemic therapies, such as pentostatin, gemcitabine, and fludarabine, alone or in combination with INF-alpha, were preferred. Of the 113 patients, eight (7% of the total and 57.1% of the advanced stage cases) died of MF; 21.4% of the late stage patients showed partial remission and 14.2% showed CR. None of the patients diagnosed with early stage disease died of MF, but two (1.9%) progressed to late stage disease. CONCLUSIONS: PUVA and PUVA+INF-alpha are effective treatment modalities, especially for early stage MF. Once the disease has progressed, both MF and SS are very resistant to treatment regimens, including chemotherapeutic agents. It is important to diagnose and treat these diseases, especially MF, in the early stages for lasting remission.     

Systemic therapy of disseminated malignant melanoma: an evidence-based overview of the state-of-the-art in daily routine

AIMS: In the metastatic stage, malignant melanoma is resistant to systemic treatment and carries a poor prognosis. A critical, evidence-based analysis of standard approaches based on an extended search of published literature and from different Internet sources is presented. MATERIAL AND METHODS: A critical, evidence-based analysis of standard approaches and their variations to systemic therapy based on an extended search of published literature and from different Internet sources is presented. Few meta-analyses are available. Therefore, assessment of therapies is mainly based on randomized multicentre studies or clinical studies achieving an evidence level grade 1 or 2. RESULTS: Monotherapy with DTIC (dacarbazine) is the standard. Based on overall survival data, polychemotherapies cannot be recommended. Combination of polychemotherapy with the cytokines interferon-alpha and interleukin-2 substantially augments chemotherapy induced response rates, but a meta-analysis for survival does not support its therapeutic superiority. Biological therapies such as vaccinations have not yet delivered results on a higher evidence level. Thus, immunotherapies as well as chemo-immunotherapies will have to be evaluated in further studies. CONCLUSIONS: Although the therapeutic efficacy is very limited, dacarbazine cannot be rejected as standard therapy for disseminated melanoma, because no other therapeutic regimen exhibits a survival benefit over DTIC in an evidence-based analysis. This lack of therapeutic progress over the past 40 years clearly calls for further clinical studies, and patients should be enrolled into clinical trials whenever possible.     

Synergistic effects of interferon‐beta and nivolumab in oral mucosal melanoma

Mucosal melanoma is a rare aggressive cancer with a very poor prognosis. Clinical and pathological characteristics of mucosal melanoma differ from those of cutaneous melanoma and there are no established management guidelines for mucosal melanoma. Complete surgical excision is one of the most effective treatments for localized lesions, while targeted therapies and immunotherapies, such as monoclonal antibodies that target cytotoxic T‐lymphocyte‐associated molecule‐4, and the programmed death (PD)‐1/PD‐ligand 1 pathway inhibitors, are treatment options for unresectable or metastatic lesions. Here, we describe the case of a patient with oral mucosal melanoma with multiple metastases. In our case, local injection of interferon (IFN)‐β with dacarbazine–nimustine–vincristine therapy provided antitumor effects on an invasive tumor on the upper gingiva. Nivolumab therapy produced complete remission of lymph node and bone metastases. In contrast, the remaining in situ portion of oral mucosal melanoma on the hard palate was refractory to IFN‐β monotherapy and nivolumab therapy. However, after administration of nivolumab, peritumoral injection of IFN‐β showed rapid therapeutic effects. Our case suggested that nivolumab upregulated the antitumor effects of IFN‐β, which induced the recruitment of CD8⁺ T cells into the tumor microenvironment contributing to the deletion of tumor cells. Combination therapy of IFN‐β and nivolumab may be a potential treatment option for patients with oral mucosal melanoma.     

Systemic isotretinoin treatment of oral and cutaneous lichen planus

Lichen planus of the skin and mucous membranes may be disabling. Severe pruritus or bullous lesions may be incapacitating when they occur while erosive oral lesions may be extremely painful. Various treatment modalities have been attempted including corticosteroids (parenteral, intralesional, and topical) and photochemotherapy. Recent successful therapeutic trials of topical retinoic acid and oral etretinate have been completed. Two patients with cutaneous and severe erosive oral lichen planus unresponsive to conventional therapies responded to a trial of oral isotretinoin with prompt and successful remission of cutaneous and oral lesions. This suggests that systemic isotretinoin may have a unique position in the treatment of mucous membrane lichen planus that is refractory to conventional therapies.     

Review of antifungal therapy, part II: treatment rationale, including specific patient populations

This portion of the antifungal review focuses on treatment rationale and suggestions, including special populations such as the elderly, children, and pregnant and immunocompromised individuals. In elderly individuals, the pathogen may be associated with certain comorbidities; treatment should begin with local treatments such as debridement (mechanical or chemical) and a topical. In children, the pathogen most commonly isolated is Trichophyton rubrum. Children should be examined for concomitant tinea and treatment options can begin with a chemical debridement (non-painful) and a topical, with non-responders being treated with combination therapy as in adults. It is suggested that blood tests are monitored at baseline and every 4-8 weeks in children on systemic therapy. Terbinafine is the only systemic in category B and local therapies should be the primary treatment modalities in pregnancy. Prevalence of onychomycosis is high in immunocompromised patients with higher relapse rates after treatment. The same fungal infections that are seen in healthy populations are usually represented in the immunocompromised host. There is a stepwise approach that is suggested in the treatment of onychomycosis. Before treatment, several factors should be determined, which include risk for failure and compliance issues. Strategies for therapy include monotherapy, combination therapy, supplemental therapy, and intermittent therapy. Topical monotherapy is effective in early distal nail disease and for the prevention of reinfection of the cured nail. Combination therapy is an appropriate progression of therapy for patients who failed monotherapy or are at risk for failure. Combined therapies are shown to increase cure rates. Mechanical interventions are essential in reducing fungal burdens to allow other modalities to penetrate, especially in dermatophytomas and onycholysis.     

Mycosis fungoides and Sézary syndrome: focus on the current treatment scenario

Cutaneous T-cell lymphomas are a heterogeneous group of lymphoproliferative disorders, characterized by infiltration of the skin by mature malignant T cells. Mycosis fungoides is the most common form of cutaneous T-cell lymphoma, accounting for more than 60% of cases. Mycosis fungoides in the early-stage is generally an indolent disease, progressing slowly from some patches or plaques to more widespread skin involvement. However, 20% to 25% of patients progress to advanced stages, with the development of skin tumors, extracutaneous spread and poor prognosis. Treatment modalities can be divided into two groups: skin-directed therapies and systemic therapies. Therapies targeting the skin include topical agents, phototherapy and radiotherapy. Systemic therapies include biological response modifiers, immunotherapies and chemotherapeutic agents. For early-stage mycosis fungoides, skin-directed therapies are preferred, to control the disease, improve symptoms and quality of life. When refractory or in advanced-stage disease, systemic treatment is necessary. In this article, the authors present a compilation of current treatment options for mycosis fungoides and Sézary syndrome.     

Komplette Remission kutaner Satelliten- und In-transit-Filiae nach intraläsionaler Interleukin-2-Applikation bei 2 Patienten mit malignem Melanom

Multiple cutaneous satellite and in-transit metastases of melanoma without involvement of lymph nodes or other organs are a challenge especially when they occur in elderly inoperable patients with multiple internal diseases. In this particular situation, intralesional application of interleukin-2 may represent an effective alternative to systemic chemo- or immunotherapy as it can be performed on an out-patient basis and has few side effects. We treated two elderly female patients with multiple cutaneous metastases of malignant melanoma with intra- and perilesional application of interleukin-2 (3 x 6-12 Mio IE) over 12 weeks and achieved a complete remission of these metastases. In follow-up biopsies, no viable tumor cells were found. Despite a slight burning at the injection side and a transient local inflammatory reaction, the therapy was well tolerated in both cases after premedication with paracetamol 500 mg orally and pretreatment of the injection site with a cream containing lidocaine and prilocaine. No systemic side effects were observed.     

Comparison of the efficacy of local narrowband ultraviolet B (NB-UVB) phototherapy versus psoralen plus ultraviolet A (PUVA) paint for palmoplantar psoriasis

Palmoplantar psoriasis is an idiopathic disabling condition, often resistant to conventional therapies. The purpose of this study was to evaluate the efficacy and safety of local narrowband ultraviolet B (NB-UVB) phototherapy and to compare it with local psoralen plus ultraviolet A (PUVA) paint in patients with palmoplantar psoriasis unresponsive to conventional therapies other than phototherapy. A cohort of 25 patients with palmoplantar psoriasis were included in this study, which was based on a left-to-right comparison pattern. The treatments were administered with local narrowband UVB irradiation on one side and local PUVA on the other side three times a week over 9 weeks. Clinical assessments were performed at baseline and every 3 weeks during the 9-week treatment. There was a statistically significant decrease in the mean clinical scores at the third, sixth and ninth week with both treatments. The difference in clinical response between the two treatment modalities was statistically significant at the end of the treatment period, with the percentage reduction in severity index scores with the PUVA-paint-treated side being 85.45% compared with 61.08% for the NB-UVB treated side (t = 5.379, P = 0.0001, Student's t-test for unpaired samples). Our results show that, although some clinical improvement was achieved with local NB-UVB phototherapy, the results were better with local PUVA, and such a treatment option may be reserved for patients with palmoplantar psoriasis who experience phototoxic reaction to psoralens.     

Combination of interferon-alpha with cytostatic drugs: a potentially successful therapeutic approach in metastatic melanoma]

Pharmacological treatment of disseminated melanoma is characterized by rather low objective response rates with mono- and combined chemotherapy and by significant toxicity. For these reasons, many centres do not now offer any systemic treatment to melanoma patients with distant metastases. Systemic treatment with interferons has not fulfilled all that was expected of it, but type-I interferons (-alpha, -beta) have proved to be effective in about 10-15% of patients treated. The antitumour activity of these substances seems to be related mainly to their antiproliferative effect, whereas no immunomodulatory effects have been substantiated in clinical trials. Combined therapy with interferons and cytostatic drugs was introduced into clinical trials only a few years ago, and the initial results are promising. Large studies with a total of over 200 patients have already been performed to evaluate the combination of interferon-alpha and dacarbazine. This treatment was effective in around 50% of the patients, complete or partial remission being achieved in 30% and stabilization of the disease, in 20%. Toxicity is significant, but still manageable; the new generation of antiemetic drugs (serotonin receptor blockers), in particular appears promising. Up to now, no improvement of efficacy has been found following addition of interferon-alpha to cisplatin in four clinical trials. In a study in our own department, however, the combined action of interferon alpha and vindesine was found to be superior to that of either used as a single agent, and the combination was well tolerated on an outpatient basis.(ABSTRACT TRUNCATED AT 250 WORDS)