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Information on human tumours 4

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tumour type

Melanoma

Data in brief: Intralesional interleukin-2 in metastatic malignant melanoma. Intralesional IL-2 in metastases results in complete remissions in 2 patients. 85% of metastases have complete remission after intratumoral IL-2 Imiquimod plus IL-2 increases response rate compared to imiquimod as single therapeuticum in fase I/II study.

2007

Green DS, Bodman-Smith MD, Dalgleish AG, Fischer MD. Phase I/II study of topical imiquimod and intralesional interleukin-2 in the treatment of accessible metastases in malignant melanoma. Br J Dermatol. 2007 Feb;156(2):337-45. BACKGROUND: Patients with metastatic skin disease in malignant melanoma can be difficult to treat effectively, often requiring repeated treatments with different modalities in an attempt to control their disease. Treatment of nonsurgically resectable melanoma deposits is unsatisfactory, as they are often multiple and recurring. Anecdotal evidence from individual use of imiquimod in superficial metastases and intralesional interleukin (IL)-2 in subcutaneous deposits suggests that the combination may be more effective in bulky subcutaneous disease. OBJECTIVES: To investigate the combination of topical imiquimod and, for selected lesions, intralesional IL-2, to treat a small cohort of patients with accessible melanoma metastases resistant to other treatments. METHODS: Thirteen patients were recruited: all had evidence of multiple cutaneous and/or subcutaneous metastases. Imiquimod was applied to the metastases on a daily basis for 4 weeks, before the introduction of intralesional IL-2. This was injected up to three times a week, into selected lesions, with 0.1 mL injected per lesion at a concentration of 3.6 MIU mL(-1), a total of 1 mL being given at each session. The treated lesions were assessed individually at intervals of 3 months. RESULTS: Thirteen patients were treated, with 10 being eligible for assessment. In total, 182 lesions were treated: 137 purely cutaneous lesions and 41 subcutaneous lesions. Overall, a clinical response was seen in 92 lesions (50.5%) with 74 (40.7%) of these being a complete response (CR) with 91% of the CRs being in the cutaneous lesions. New lesions did appear during the treatment course; however, patients with cutaneous disease experienced a marked slowing of the appearance of new cutaneous lesions. No cutaneous lesions that responded reappeared on cessation of treatment. CONCLUSIONS: The combination of imiquimod and IL-2 is effective in controlling this mixed cutaneous and subcutaneous disease, and is well tolerated. Imiquimod alone is often enough to elicit a response in purely cutaneous lesions. The addition of intralesional IL-2 increases the response rates in subcutaneous lesions, and in otherwise refractory cutaneous lesions.

Green et al. (2007) Br.J.Dermatol. 156, 337-45

2004

Pfohler C, Steinhauser S, Wagner A, Ugurel S, Tilgen W. Complete remission of cutaneous satellite and in-transit metastases. After intralesional therapy with interleukin-2 in 2 patients with malignant melanoma Hautarzt. 2004 Feb;55(2):171-5. 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.

Phoehler et al. (2004) Hautartz 55, 171-5

2003

Radny P, Caroli UM, Bauer J, Paul T, Schlegel C, Eigentler TK, Weide B, Schwarz M, Garbe C. Phase II trial of intralesional therapy with interleukin-2 in soft-tissue melanoma metastases. Br J Cancer. 2003 Nov 3;89(9):1620-6. The objective of the present study was to validate the use of intralesional injection of interleukin-2 (IL-2) in patients with skin and soft-tissue melanoma metastases. A total of 24 patients with AJCC stage III or IV melanoma and single or multiple skin and soft-tissue metastases were included. Interleukin-2 injections were administered intralesionally into the total number of cutaneous and soft-tissue metastases accessible from the skin, 2-3 times weekly, over 1-57 weeks. Single doses varied from 0.6 to 6 x 10(6) IU, depending on lesion size. The clinical response was monitored by sonography and confirmed by histopathology; response evaluation was confined to the intralesionally treated tumours. Complete response (CR) of the treated metastases was achieved in 15 patients (62.5%), the longest remission lasting 38 months to date. In five patients, partial response (PR) was achieved (21%) and in another three patients, progressive disease was observed (one patient not assessable). A total of 245 metastases were treated with CR in 209 (85%), and PR in 21 (6%). The therapy was generally well tolerated; the observed adverse events were mainly of grade 1-2 severity. Immunohistochemical studies showed the tumour cells undergoing apoptosis and revealed a mixed character of the inflammatory infiltrate. The unusual high CR rate in metastatic melanoma of 62.5% and the limited toxicity suggest that treatment of skin and soft-tissue melanoma metastases with intralesional injection of IL-2 may be a safe and effective alternative to conventional therapies. The optimal dosage and duration of this therapy still remain to be defined in larger prospective multicentre trials.

Br.J.Cancer 2003; 89, 1620-6

tumour type

Interleukin-2 (IL-2) Mechanism of IL-2 therapy of cancer Cancers sensitve to IL-2 Surgery and IL-2 Radiotherapy and IL-2 Chemotherapy and IL-2 Experts I want to co-operate (doctors) Frequently Asked Questions (FAQs)

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Our research is supported by Stichting ter bevordering van het onderzoek in de Experimentele Pathologie en in het bijzonder in de TumourImmunologie. Stichting EPTI, IJselstein, The Netherlands