Melanoma interferon alfa

Melanoma Interferon alfa-2a-. Subcutaneous, IM 12 million units/m 3 times/wk for 3 mo. Interferon alfa-2b-. IV Initially, 20 million units/m 5 times/wk for 4 wk. Maintenance 10 million units IM/SCfor48 wk. 

Interferon alfa-2b is useful in the treatment of a rare form of chronic leukemia, hairy cell leukemia, in which it produces remissions in 60 to 80% of patients. However, it has minimal antitumor activity in most human cancers. Remissions lasting a few months have been observed in 10 to 20% of patients with lymphomas, multiple myeloma, melanoma, renal cell carcinoma, and ovarian carcinoma. 

Interferon alfa-2a Treatment of active, chronic hepatitis, bladder or renal carcinoma, malignant melanoma, multiple myeloma, mycosis fungoides, non-Hodgkin s lymphoma... 

Legha, S.S., S. Ring, O. Eton, A. Bedikian, A.C. Buzaid, C. Plager, and N. Papadopon-los. Development of a biochemotherapy regimen with concurrent administration of cisplatin, vinblastine, dacarbazine, interferon alfa, and interleukin-2 for patients with metastatic melanoma. J Chn Oncol, 1998.16(5) 1752-9. 

F. Role in therapy According to Micromedex, Roferon-A is recommended as the drug of choice in renal carcinoma and the chronic phase of chronic myelogenous leukemia. The role of Gleevec (Ima-tinib) in CML is yet to be determined, but it may replace the use of interferon alfa-2a. Roferon-A is an alternative (for unrespon-sive/intolerant patients) to current regimens of choice in hairy-cell leukemia, multiple myeloma, metastatic melanoma, and AIDS-related Kaposi s sarcoma. Other alpha interferons appear to have similar efficacy and can be used in lieu of Roferon-A in some instances. In particular, interferon alfa-2b (Intron) can be considered to have the same role as interferon alfa-2a in chronic hepatitis C, Kaposi s sarcoma, and hairy-cell leukemia. 

H. Other considerations Interferon alfa-2a has been designated an orphan drug product for the treatment of chronic myelogenous leukemia, AIDS-related Kaposi s sarcoma, renal cell carcinoma, metastatic malignant melanoma, and esophageal and colorectal cancer. 

Severe hypertriglyceridemia (7.5-19 mmol/1 653-1644 mg/dl) has been reported in three patients receiving adjuvant high-dose interferon alfa for malignant melanoma... 

Several mechanisms involved in the pathogenesis of interferon alfa-induced psychiatric adverse effects have been hypothesized (Loftis 175), but the mechanisms by which interferon alfa enters the brain to produce neurotransmitter changes are unclear. In a prospective study in 48 patients who received adjuvant interferon alfa for malignant melanoma there was a positive correlation between the increase in serum concentration of soluble ICAM-1 and depression scores the authors suggested that induction of soluble ICAM-1 by interferon alfa increased the permeability of the blood-brain barrier, allowing the drug to enter the brain more readily (358). 

Interferons. Interferon alfa is used for chronic granulocytic leukaemia, hairy cell leukaemia, renal-cell carcinoma and Kaposi s sarcoma. It may also be an effective aduvant therapy for patients at high risk of melanoma recurrence. 

Interferon alfa-2b Intron A (Schering-Plough) Hairy cell leukemia AIDS-related Kaposi s sarcoma chronic hepatitis, types B and C condylomata acuminata malignant melanoma follicular lymphoma non-Hodgkins lymphoma... 

The severity of hematological disorders was not affected by previous chemotherapy for metastatic melanoma or renal cell carcinoma and there was no correlation with response to treatment (60). However, others have found that moderate to severe dose-related thrombocjdo-penia occurred particularly in patients previously treated with cytotoxic agents (64). Subcutaneous low-dose aldesleukin therapy reduced the frequency and intensity of hematological toxicity, and the combination of aldesleukin plus interferon alfa produced either moderate additional toxicity or no significant enhancement (65). 

Aldesleukin given alone or aldesleukin plus interferon alfa produced a high incidence of vitihgo in patients with metastatic melanoma, irrespective of whether or not they had received chemotherapy (102-104). A possible correlation between aldesleukin-induced vitihgo and a favorable tumor response was found (102) but has also been disputed (103). 

In a phase III trial in 190 patients with metastatic melanoma, sequential chemotherapy with dacarbazine, cisplatin, and vinblastine plus interferon alfa and aldesleukin modestly increased the response rates and produced considerably more frequent and severe adverse effects than chemotherapy alone (128). In particular, severe episodes of anemia and thrombocytopenia that required blood or platelet transfusions were 2-6 times more frequent in the chemotherapy group. 

Rosenberg SA, Yang JC, Schwartzentruber DJ, Hwu P, Marincola FM, Topalian SL, Seipp CA, Einhorn JH, White DE, Steinberg SM. Prospective randomized trial of the treatment of patients with metastatic melanoma nsing chemotherapy with cisplatin, dacarbazine, and tamoxifen alone or in combination with interleukin-2 and interferon alfa-2b. J Clin Oncol 1999 17(3) 968-75. 

Whereas clinically insignificant coagulation abnormalities have been documented in patients receiving high-dose continuous interferon alfa (35), isolated cases of venous thrombosis have been observed (SEDA-20, 329) (36). Interferon alfa can also induce the production of antiphospholipid antibodies (SEDA-20, 329) (SEDA-21, 371). In one study, antiphospholipid antibodies were found in five of 12 patients with melanoma treated with interferon alfa alone or with interferon alfa plus interleukin-2 deep venous thrombosis occurred in four patients with antiphospholipid antibodies (37). Although the underlying neoplasia undoubtedly played a role in the further development of venous thrombosis, the causative role of interferon alfa was suggested by the absence of... 

A 60-year-old smoker was treated with interferon alfa (100 MU/week for 2 months and 9 MU/week for 15 weeks) for cutaneous melanoma. Ocular examination was normal before treatment, but he developed acute loss of peripheral vision in his left eye after 23 weeks. Examination was consistent with anterior ischemic optic neuropathy, and there was optic disc edema, a pupillary defect, and circular visual field constriction in the left eye. There was renal artery constriction in both eyes. Despite treatment with aspirin, high-dose dexamethasone, heparin, and finally withdrawal of interferon alfa, loss of visual function progressed and affected both eyes. Ciclosporin was started, but he was considered to have irreversible loss of visual function. 

This report shows that interferon alfa can be a potent precipitator of extremely severe ocular disorders and also argues for careful ocular surveillance in patients receiving adjuvant interferon alfa for high-risk resected melanoma. 

Vitiligo has sometimes been reported in patients with malignant melanoma, for example in 17-25% of patients receiving interferon alfa alone (SEDA-21, 372). There have also been a few reports of vitihgo in patients with chronic hepatitis C (SEDA-20, 330), and one patient had both scleroderma and vitiligo (SEDA-19, 336). 

Radiation recall dermatitis developed in a 29-year-old woman after high-dose intravenous interferon alfa-2b was given 5 days after the completion of radiotherapy for malignant melanoma (300). 

A 26-year-old man with a malignant melanoma had two episodes of acute severe rhabdomyolysis after each exposure to a chemotherapy regimen containing interferon alfa and dacarbazine (310). As a few cases of... 

Acute rhabdomyolysis occurred in a 34-year-old woman with a melanoma treated with interferon alfa 20 MU/m / day (311). There was no recurrence on retreatment with a lower dose (down to 6.6 MU/m /day), suggesting that this was a dose-related complication. 

Polymyositis has very rarely been associated with interferon alfa, but has been reported together with autoimmune thyroiditis in a 48-year-old woman after treatment for 5 months for malignant melanoma (349). 

Lohmann CP, Kroher G, Bogenrieder T, Spiegel D, Preuner J. Severe loss of vision during adjuvant interferon alfa-2b treatment for malignant melanoma. Lancet 1999 353(9161) 1326. 

Hairy cell leukemia is the present indication for interferon alfa-2b. It is also useful in treadng malignant melanoma and renal cell carcinoma. Hyperseresitivity to this protein has not been ob.served. Patients develop a flu-like syndrome, CNS effects, and cardiovascular effects, including hypotension, arrhythmia, or tachycardia. 

Interferon alfa 2b (interferon alfa-2b [usan] Alferon Intron A Viraferon Sch 30500) is a recombinant (rbe) version, and is extensively used by injection as an anticancer agent to treat hairy cell leukaemia, condylomata acuminata, AIDS-related Kaposi s sarcoma, follicular lymphoma, chronic myelogenous leukaemia, lymph or liver metastases of carcinoid tumour, as an anticancer adjunct in malignant melanoma also, in the maintenance of remission in multiple myeloma chronic active hepatitis B, chronic hepatitis C. 

Kirkwood JM, Straderman MH, Ernstoff MS, et al. Interferon alfa-2b adjuvant therapy of high-risk resected cutanteous melanoma The Eastern cooperative oncology group trial EST 1684. J Clin Oncol 1996 14 7-17. 

Kirkwood JM, Ibrahim JG, Sondak VK, et al. High- and low-dose interferon alfa-2b in high risk melanoma first analysis of intergroup trial E1690/S9111/C9190. J Clin Oncol 2000 18 2444-2458. 

Moschos SJ, Kirkwood JM. Present status and future prospects for adjuvant therapy of melanoma Time to build upon the foundation of high-dose interferon alfa-2b. J Clin Oncol 2004 22 11-14. 

Cole BF, Gelber RD, Kirkwood JM, et al. A quaUty-of-hfe-adjusted survival analysis of interferon alfa-2b adjuvant treatment for high-risk resected cutaneous melanoma An Eastern cooperative oncology group study (E1684). J Clin Oncol 1996 14 2666-2673. 

An effective treatment for the deadly skin cmicer melanoma is clearly needed. Current best therapy is surgical removal of high-risk melanoma and treatment with Interferon alfa. Melanoma patients have a 50-80% chance of relapse without adjuvant treatment. The (jMK vaccine is in development for melanoma... 

GMK vaccine was compared with high-dose Interferon alfa 2b in high-risk melanoma patients who had undergone surgery. Interferon-treated patients were 50% less likely to experience a return of their disease and 52% less likely to die than were GMK-treated patients (55). 

Interferon alfa-2b is an immunomodulator. It causes inhibition of virus replication in virus-infected cells, suppression of cell proliferation, and such immunomodulating activities as enhancement of the phagocytic activity of macrophages and augmentation of the specific cytotoxicity of lymphocytes for target cells. It is indicated in hairy cell leukemia condylomata acuminata AIDS-related Kaposi sarcoma chronic hepatitis B chronic non-A/non-B hepatitis (hepatitis C) and malignant melanoma and follicular non-Hodgkin s lymphoma. 

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