RATIONALE: Interferon alfa may interfere with the growth of the cancer cells. It is not yet known if this treatment is more effective than observation following surgery for stage III melanoma.
PURPOSE: Randomized phase III trial to determine the effectiveness of interferon alfa in treating patients who have undergone surgery for stage III melanoma.
* Compare the effect of adjuvant therapy with pegylated interferon alfa vs observation, in terms of distant metastases-free survival, in patients with previously resected stage III melanoma.
* Compare the overall survival in these patients after treatment with pegylated interferon alfa vs observation.
* Determine the compliance of these patients treated with pegylated interferon alfa.
* Compare the quality of life in these patients after treatment with pegylated interferon alfa vs observation.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to type of nodal involvement (N1 vs N2), number of positive nodes (1 vs 2-4 vs 5 or more vs not assessed), Breslow primary (T1-2 vs T3 vs T4 vs unknown), ulceration of primary tumor (absent vs present vs unknown), sex, and center. Patients are randomized to one of two treatment arms.
* Arm I: Patients receive pegylated interferon alfa subcutaneously weekly for 5 years.
* Arm II: Patients undergo observation only. Treatment continues in the absence of distant metastases or unacceptable toxicity.
Quality of life is assessed at baseline, and then at months 3, 12, 24, 36, 48, and 60.
PROJECTED ACCRUAL: A total of 1,200 patients (600 per treatment arm) will be accrued for this study within 1. 5-2 years.
DISEASE CHARACTERISTICS:
* Histologically confirmed previously resected stage III primary cutaneous melanoma or unknown primary with regional lymph node involvement
- N1 disease
+ Microscopic, nonpalpable nodal involvement
+ Primary melanoma of any stage with clinically inapparent N1 regional lymph node metastases (T1-4, N1, M0) detected by elective lymph node dissection or sentinel node biopsy
- N2 disease
+ Palpable nodal involvement with synchronous primary melanoma or apparent nodal disease after prior excision (any pT, N2, M0)
- Regional lymph node recurrence at any interval after surgery for primary melanoma of any depth (T1-4, rN2, M0)
* Complete resection of primary melanoma with adequate surgical margins
* Full lymphadenectomy must be performed within 70 days of study
* No mucous membrane melanoma or ocular melanoma
* No evidence of distant or nonregional lymph node metastases or in transit metastases (even if previously resected)
* No incompletely resected disease due to gross extracapsular extension
PATIENT CHARACTERISTICS:
Age:
* 18 to 70
Performance status:
* ECOG 0-1
Life expectancy:
* Not specified
Hematopoietic:
* WBC at least 3,000/mm^3
* Platelet count greater than 100,000/mm^3
* Hemoglobin at least 9 g/dL
Hepatic:
* SGOT and SGPT less than 2 times upper limit of normal
* No active hepatitis
Renal:
* Creatinine less than 2. 0 mg/dL
Cardiovascular:
* No severe cardiovascular disease including the following:
- Arrhythmias requiring chronic treatment
- Congestive heart failure (New York Heart Association class III or IV)
- Symptomatic ischemic heart disease
Other:
* No other prior malignancy within the past 5 years except surgically cured nonmelanomatous skin cancer or carcinoma in situ of the cervix
* No thyroid dysfunction unresponsive to therapy
* No uncontrolled diabetes mellitus
* No active autoimmune disease
* No active and/or uncontrolled infection
* No history of neuropsychiatric disorder requiring hospitalization
* No known active alcohol or drug abuse
* HIV negative
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
* No prior interferon alfa
* No prior immunotherapy for melanoma
* No other concurrent immunologic or biologic therapy
* No concurrent colony stimulating factors including epoetin alfa and filgrastim (G-CSF)
Chemotherapy:
* No prior chemotherapy for melanoma
* No concurrent chemotherapy
Endocrine therapy:
* No prior hormonal therapy for melanoma
* No concurrent hormonal therapy
* No concurrent chronic systemic corticosteroid therapy
Radiotherapy:
* No prior radiotherapy for melanoma
* No concurrent radiotherapy
Surgery:
* See Disease Characteristics
* Recovered from any prior recent surgery
Other:
* At least 30 days since other prior experimental therapy
* No other concurrent investigational drugs
Addenbrooke's NHS Trust, Cambridge, England CB2 2QQ, United Kingdom
Bristol Haematology and Oncology Centre, Bristol, England BS2 8ED, United Kingdom
Cheltenham General Hospital, Cheltenham, England GL53 7AN, United Kingdom
Clatterbridge Centre for Oncology NHS Trust, Merseyside, England CH63 4JY, United Kingdom
Guy's and St. Thomas' Hospitals NHS Trust, London, England SE1 9RT, United Kingdom
Leicester Royal Infirmary, Leicester, England LE1 5WW, United Kingdom
Newcastle General Hospital, Newcastle Upon Tyne, England NE4 6BE, United Kingdom
Princess Royal Hospital, Hull, England HU8 9HE, United Kingdom
Royal Devon and Exeter Hospital, Exeter, England EX2 5DW, United Kingdom
Royal Free Hospital, London, England NW3 2QG, United Kingdom
Royal Marsden Hospital, Sutton, England SM2 5PT, United Kingdom
Royal Marsden NHS Trust, London, England SW3 6JJ, United Kingdom
Royal Surrey County Hospital, Guildford, England GU2 5XX, United Kingdom
Saint Bartholomew's Hospital, London, England EC1A 7BE, United Kingdom
Salisbury District Hospital, Salisbury, England SP2 8BJ, United Kingdom
Southampton General Hospital, Southampton, England SO16 6YD, United Kingdom
Southend NHS Trust Hospital, Westcliff-On-Sea, England SS0 0RY, United Kingdom
St. George's Hospital, London, England SW17 0QT, United Kingdom
St. James's Hospital, Leeds, England LS9 7TF, United Kingdom
Weston Park Hospital, Sheffield, England S1O 2SJ, United Kingdom
Centre Hospitalier Regional et Universitaire de Saint-Etienne, Saint Priest en Jarez 42277, France
Centre Hospitalier Universitaire, Reims 51092, France
Centre Hospital Regional Universitaire de Limoges, Limoges 87042, France
Centre Hospitalier Universitare d'Amens, Amiens 80054, France
Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle, Montpellier 34298, France
Centre Rene Huguenin, Saint Cloud 92211, France
Hopital Saint-Louis, Paris 75475, France
Hopital St. Eloi, Montpellier 34295, France
Hopitaux Universitaire de Strasbourg, Strasbourg 67091, France
Institut Gustave Roussy, Villejuif F-94805, France
National Centre of Oncology, Sofia 1756, Bulgaria
Centre Hospitalier Regional Metz Thionville, Thionville 57126, France
Cliniques Universitaires Saint-Luc, Brussels 1200, Belgium
David Maddison Clincial Sciences, Newcastle NSW 2300, Australia
Centre Hospitalier Universitaire Bretonneau de Tours, Tours 37044, France
Universitair Ziekenhuis Antwerpen, Edegem B-2650, Belgium
Hopital Universitaire Erasme, Brussels 1070, Belgium
U.Z. Gasthuisberg, Leuven B-3000, Belgium
Centre Leon Berard, Lyon 69373, France
Centre Eugene Marquis, Rennes 35042, France
Institut Jules Bordet, Brussels 1000, Belgium
CHU Ambroise Pare, Boulogne Billancourt F-92104, France
CHR de Besancon - Hopital Saint-Jacques, Besancon 25030, France
Otto - Von - Guericke - Universitaet Magdeburg, Magdeburg D-39120, Germany
Institute of Oncology, Ljubljana, Ljubljana Sl-1000, Slovenia
Hospital Clinico Universitario, Zaragoza 50009, Spain
Hospital Universitario 12 de Octubre, Madrid 28041, Spain
Inselspital, Bern, Bern CH-3010, Switzerland
Kantonspital Aarau, Aarau 5001, Switzerland
Ratisches Kantons und Regionalspital, Chur CH-7000, Switzerland
UniversitaetsSpital, Zurich CH-8091, Switzerland
Ege University Medical School, Izmir 35220, Turkey
Vakif Gureba Training Hospital, Istanbul 34296, Turkey
Churchill Hospital, Oxford OX3 7LJ, United Kingdom
Istituto Nazionale per lo Studio e la Cura dei Tumori, Naples 80131, Italy
Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano (Milan) 20133, Italy
Istituto Regina Elena, Rome 00161, Italy
Ospendale S.M. Annunziata-A.S.DI Firenze, Firenze I-50011, Italy
Universita Degli Studi di Torino, Torino 10126, Italy
Academisch Ziekenhuis Utrecht, Utrecht 3584 CX, Netherlands
Erasmus University Medical Center, Rotterdam 3075 EA, Netherlands
Leiden University Medical Center, Leiden 2300 CA, Netherlands
University Medical Center Nijmegen, Nijmegen NL-6500 HB, Netherlands
Vrije Universiteit Medisch Centrum, Amsterdam 1007 MB, Netherlands
Great Poland Cancer Center, Poznan 61 866, Poland
Rambam Medical Center, Haifa 31096, Israel
Tel-Aviv Sourasky Medical Center, Tel-Aviv 64239, Israel
Wolfson Medical Center, Holon 58100, Israel
Centro di Riferimento Oncologico - Aviano, Aviano 33081, Italy
European Institute of Oncology - Chemo Prevention, Milano 20141, Italy
Istituto Nazionale per la Ricerca sul Cancro, Genoa (Genova) 16132, Italy
Hopital Saint Andre, Bordeaux 33075, France
Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw 02-781, Poland
Instituto Portugues de Oncologia Centro do Porto, SA, Porto 4200, Portugal
Instituto Portugues de Oncologia de Francisco Gentil - Centro de Lisboa, Lisbon 1099-023 Codex, Portugal
Robert Roessle Klinik, Berlin D-13122, Germany
Saint Josef Hospital, Bochum 1 D-44791, Germany
Stadt. Kliniken, Dortmund 44123, Germany
Georg August Universitaet, Goettingen D-37075, Germany
Haematologisch-Onkologische Praxis Altona, Hamburg D-22765, Germany
Klinikum der Stadt Mannheim, Mannheim D-68135, Germany
Universitaet Erlangen, Erlangen D-91054, Germany
Universitaet Leipzig - Chirurgische Klinik und Poliklinik I, Leipzig D-04103, Germany
Universitaet Wuerzburg/Hautkrankheiten, Wuerzburg D-97080, Germany
Universitaets-Hautklinik Heidelberg, Heidelberg D-69115, Germany
CHR de Grenoble - La Tronche, Grenoble 38043, France
Centre Alexis Vautrin, Vandoeuvre-les-Nancy 54511, France
Centre Hospitalier Regional et Universitaire de Lille, Lille 59037, France
University Hospital Sestre Milosrdnice, Zagreb 10000, Croatia
North-Estonian Regional Hospital Cancer Centre, Tallinn 11619, Estonia
Hopital Bichat - Claude Bernard, Paris 75018, France
Hopital Haut Leveque, Pessac 33604, France
Hopital L'Archet - 2, Nice F-06202, France
Clinique Notre Dame de Grace, Gosselies 6041, Belgium
Charles University Hospital, Prague (Praha) 128 08, Czech Republic
Selly Oak Hospital at University Hospital NHS Trust, Birmingham B29 6JD, United Kingdom
Belfast City Hospital Trust, Belfast, Northern Ireland BT9 7AB, United Kingdom
Ninewells Hospital and Medical School, Dundee, Scotland DD1 9SY, United Kingdom
Western Infirmary, Glasgow, Scotland G11 6NT, United Kingdom
Austin and Repatriation Medical Centre, Heidelberg West, Victoria 3081, Australia
Peter MacCallum Cancer Institute, East Melbourne, Victoria 8006, Australia
Velindre Cancer Center at Velinde Hospital, Cardiff, Wales CF4 7XL, United Kingdom
Royal Perth Hospital, Perth, Western Australia 6000, Australia
Sir Charles Gairdner Hospital, Perth, Perth, Western Australia 6009, Australia
