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Cisplatin, dacarbazine, and fotemustine plus interferon alpha in patients with advanced malignant melanoma. A multicenter phase II study of the Italian Cooperative Oncology Group.

Abstract

BACKGROUND

In a previous study, the authors tested the combination of fotemustine (FM) 100 mg/m(2) intravenously (i.v.) on Day 1, dacarbazine (DTIC) 250 mg/m(2) i.v. on Days 2-5, and interferon alpha (IFNalpha) 3 MIU intramuscularly three times per week in 43 patients with advanced melanoma. An overall response rate of 40% and a median survival of 40 weeks were obtained. To evaluate whether the addition of cisplatin (CDDP) to this regimen could improve these results, the authors conducted a preliminary Phase I study and concluded that CDDP 25 mg/m(2) i.v. for 2 days can be combined safely with DTIC, FM, and IFNalpha. Herein, the authors report the results of a Phase II trial with this regimen.

METHODS

From June 1996 to February 1999, 64 patients with metastatic melanoma who were not amenable to surgery were enrolled in this study. Sixty eligible patients (32 males and 28 females; median age, 53 years) were treated with a combination of FM 100 mg/m(2) i.v. on Day 1, DTIC 300 mg/m(2) i.v. on Days 2-4, and CDDP 25 mg/m(2) i.v. on Days 3 and 4 recycled every 3 weeks. IFN alpha2b was administered at a dose of 3 MIU intramuscularly 3 times per week until disease progression.

RESULTS

A total of 189 courses were administered, with a median number of 3 courses per patient (range, 1-8 courses per patient). Eleven complete responses and 12 partial responses were observed, for an overall response rate of 38.3% (95% exact confidence interval, 26.1-51.8%). The median survival was 36 weeks. Neutropenia and thrombocytopenia affected 85% of patients and 68% patients and was World Health Organization Grade 3-4 in 40% and 50%, respectively. The side effects attributable to IFN alpha2b were mild and manageable. The other side effects were moderate and well controlled by supportive therapy.

CONCLUSIONS

The schedule used in this study demonstrated significant activity in patients with advanced, untreated melanoma. The addition of CDDP in the management of the patients in this series seemed to increase significantly both the proportion of patients who achieved a complete response and the probability of long term survival compared with a previous series of patients who were treated by the authors. However, considering the currently available therapies, this regimen does not seem to offer a special advantage in the treatment of patients with this disease. New agents and new protocols are needed.

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    Source

    Cancer 89:12 2000 Dec 15 pg 2630-6

    MeSH

    Adult
    Aged
    Anemia
    Antigens, CD
    Antigens, CD146
    Antigens, Neoplasm
    Antigens, Surface
    Antineoplastic Combined Chemotherapy Protocols
    Cisplatin
    Dacarbazine
    Female
    Fever
    Follow-Up Studies
    Humans
    Interferon-alpha
    MART-1 Antigen
    Male
    Melanoma
    Melanoma-Specific Antigens
    Membrane Glycoproteins
    Middle Aged
    Monophenol Monooxygenase
    Nausea
    Neoplasm Proteins
    Neural Cell Adhesion Molecules
    Neutropenia
    Nitrosourea Compounds
    Organophosphorus Compounds
    RNA, Messenger
    Reverse Transcriptase Polymerase Chain Reaction
    Survival Analysis
    Thrombocytopenia
    Treatment Outcome
    Vomiting

    Pub Type(s)

    Clinical Trial
    Clinical Trial, Phase II
    Journal Article
    Multicenter Study

    Language

    eng

    PubMed ID

    11135225

    Citation

    TY - JOUR T1 - Cisplatin, dacarbazine, and fotemustine plus interferon alpha in patients with advanced malignant melanoma. A multicenter phase II study of the Italian Cooperative Oncology Group. AU - Daponte,A, AU - Ascierto,P A, AU - Gravina,A, AU - Melucci,M T, AU - Palmieri,G, AU - Comella,P, AU - Cellerino,R, AU - DeLena,M, AU - Marini,G, AU - Comella,G, AU - ,, PY - 2001/1/3/pubmed PY - 2001/3/3/medline PY - 2001/1/3/entrez SP - 2630 EP - 6 JF - Cancer JO - Cancer VL - 89 IS - 12 N2 - BACKGROUND: In a previous study, the authors tested the combination of fotemustine (FM) 100 mg/m(2) intravenously (i.v.) on Day 1, dacarbazine (DTIC) 250 mg/m(2) i.v. on Days 2-5, and interferon alpha (IFNalpha) 3 MIU intramuscularly three times per week in 43 patients with advanced melanoma. An overall response rate of 40% and a median survival of 40 weeks were obtained. To evaluate whether the addition of cisplatin (CDDP) to this regimen could improve these results, the authors conducted a preliminary Phase I study and concluded that CDDP 25 mg/m(2) i.v. for 2 days can be combined safely with DTIC, FM, and IFNalpha. Herein, the authors report the results of a Phase II trial with this regimen. METHODS: From June 1996 to February 1999, 64 patients with metastatic melanoma who were not amenable to surgery were enrolled in this study. Sixty eligible patients (32 males and 28 females; median age, 53 years) were treated with a combination of FM 100 mg/m(2) i.v. on Day 1, DTIC 300 mg/m(2) i.v. on Days 2-4, and CDDP 25 mg/m(2) i.v. on Days 3 and 4 recycled every 3 weeks. IFN alpha2b was administered at a dose of 3 MIU intramuscularly 3 times per week until disease progression. RESULTS: A total of 189 courses were administered, with a median number of 3 courses per patient (range, 1-8 courses per patient). Eleven complete responses and 12 partial responses were observed, for an overall response rate of 38.3% (95% exact confidence interval, 26.1-51.8%). The median survival was 36 weeks. Neutropenia and thrombocytopenia affected 85% of patients and 68% patients and was World Health Organization Grade 3-4 in 40% and 50%, respectively. The side effects attributable to IFN alpha2b were mild and manageable. The other side effects were moderate and well controlled by supportive therapy. CONCLUSIONS: The schedule used in this study demonstrated significant activity in patients with advanced, untreated melanoma. The addition of CDDP in the management of the patients in this series seemed to increase significantly both the proportion of patients who achieved a complete response and the probability of long term survival compared with a previous series of patients who were treated by the authors. However, considering the currently available therapies, this regimen does not seem to offer a special advantage in the treatment of patients with this disease. New agents and new protocols are needed. SN - 0008-543X UR - https://www.unboundmedicine.com/medline/citation/11135225/Cisplatin_dacarbazine_and_fotemustine_plus_interferon_alpha_in_patients_with_advanced_malignant_melanoma__A_multicenter_phase_II_study_of_the_Italian_Cooperative_Oncology_Group_ L2 - http://www.labome.org//expert/italy/ascierto/paolo-a-ascierto-220035.html ER -