Cisplatin, dacarbazine, and fotemustine plus interferon α in patients with advanced malignant melanoma

Daponte, Antonio; Ascierto, Paolo A.; Gravina, Adriano; Melucci, Maria Teresa; Palmieri, Giuseppe; Comella, Pasquale; Cellerino, R; Delena, M; Marini, G; Comella, G.

doi:10.1002/1097-0142(20001215)89:12<2630::aid-cncr16>3.3.co;2-q

Cited by 7 publications

(6 citation statements)

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“…Our patient group showed a slight predominance of male patients, as is often found in series of patients with metastatic melanoma 4,24 , 25,33–35 . The mean age in our study was in the upper range (57·6 years) compared with many other studies, 4,5,12,13,24–26,33–37 ranging between 41 and 58·8 years.…”

Section: Discussionsupporting

confidence: 67%

Temozolomide and interferon alpha2b in metastatic melanoma stage IV

et al. 2004

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Section: Discussionsupporting

confidence: 67%

Temozolomide and interferon alpha2b in metastatic melanoma stage IV

et al. 2004

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“…Various in vitro and in vivo studies indicated that Hu-IFNs potentiate the activity of clinically useful drugs in a variety of human tumors and tumor models (Borden, 1998;Qin et al, 1998;Eck et al, 2001;Tada et al, 2001). A recent report describes a biochemotherapeutic approach in which Hu-IFN-a was used as an adjuvant to chemotherapy with some success in relapsed melanoma and carcinomas (Wadler and Schwartz, 1990;Borden, 1998;Daponte et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Few clinical trials have sought to incorporate Hu-IFN into combination chemotherapy regimens against solid tumors. Various studies comparing therapy with antitumor chemotherapeutic agents versus the same treatment with Hu-IFN, demonstrated an increased objective response rate with the addition of Hu-IFN compared with cytotoxic agents alone (Wadler and Schwartz, 1990;Wadler and Schwartz, 1997;Faderl et al, 1999;Daponte et al, 2000;Todesco et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Strong inhibition of Ewing tumor xenograft growth by combination of human interferon-alpha or interferon-beta with ifosfamide

et al. 2002

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Ewing sarcoma is the second most common bone tumor in childhood. Despite aggressive chemotherapy and radiotherapy strategies, the prognosis of patients with metastatic disease remains poor. We have recently reported that Ewing tumor cell proliferation was strongly inhibited by IFN-b and to a lesser degree by IFN-a. Moreover, under IFN-b treatment, some cell lines undergo apoptosis. Since the possibility of using IFNs for Ewing tumor treatments may be of interest, we have evaluated the efficacy of Hu-IFNs in a nude mice model of Ewing tumor xenografts. The results reported here show that human type I IFNs, Hu-IFN-a and Hu-IFN-b impaired tumor xenograft take and displayed an antigrowth effect toward established xenografts. Furthermore, we have also shown that combined therapy with Hu-IFNs and ifosfamide (IFO), an alkylating agent widely used in high-dose chemotherapy of Ewing tumors, results in a strong antitumor effect. Pathological analysis showed that Hu-IFN-a/IFO and Hu-IFN-b/IFO were characterized by a dramatic decrease in the mitotic index and marked necrosis, as well as extensive fibrosis associated with numerous calcifications. To our knowledge, this is the first demonstration of a potential antitumor effect of human type I IFNs and IFO on Ewing tumors, providing a rational foundation for a promising therapeutic approach to Ewing sarcoma.

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“…However, MM frequently displays primary chemoresistance, and only a few cytotoxic drugs have shown activity against this tumor. Higher remission rates are obtained with DNA-alkylating agents, including cisplatin, methylating agents such dacarbazine and temozolomide, or chloroethylating agents such 2-chloroethylnitrosoureas (CENU) (Daponte et al, 2000;Middleton et al, 2000a). Fotemustine is a third generation nitrosourea which is used both in melanoma and brain tumors (Merimsky et al, 1992).…”

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confidence: 99%

Cytotoxicity, DNA Damage, and Apoptosis Induced by New Fotemustine Analogs on Human Melanoma Cells in Relation to O⁶-Methylguanine DNA-Methyltransferase Expression

Passagne¹,

Evrard²,

Winum³

et al. 2003

J Pharmacol Exp Ther

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Fotemustine is a third generation chloroethylnitrosourea that has demonstrated significant antitumoral effects in malignant melanoma. However, its use is somewhat limited by its toxic side effects and chemoresistance caused by direct repair of O 6 -alkyl groups by the enzyme O 6 -methylguanine DNA-methyltransferase (MGMT). The aim of this work was to determine to what extent the expression of MGMT influences cytotoxicity, DNA damage, and apoptosis induced by new nitrososulfamide analogs of fotemustine (compounds 4 and 8), which have previously demonstrated interesting antiproliferative properties. We carried out complementary strategies that consisted of MGMT cDNA transfection in CAL77 MerϪ melanoma cells and of MGMT inhibition with O 6 -benzylguanine (BG) in A375 Merϩ melanoma cells. MGMT-transfected cells were 7 to 9 times less sensitive to fotemustine than parent cells, whereas no difference between the transfected and parent cells was observed for nitrososulfamide analogs. The cytotoxicity of these analogs vis à vis a MGMT-proficient A375 melanoma cell line was approximately 3 times greater than that of fotemustine. Coincubation of these cells with O 6 -benzylguanine significantly increased the cytotoxicity of fotemustine and compound 8, whereas BG had little effect on the cytotoxicity of compound 4. Furthermore, DNA fragmentation determined by a comet assay was greater with nitrososulfamide analogs than with fotemustine. O 6 -benzylguanine increased DNA fragmentation for fotemustine and compound 8, but not for compound 4, which induced comets with a typical apoptotic appearance. The ability of this compound to induce apoptosis in the absence of BG was confirmed by a specific enzyme-linked immunosorbent assay apoptotic assay using a single-stranded DNA monoclonal antibody.

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Cisplatin, dacarbazine, and fotemustine plus interferon α in patients with advanced malignant melanoma

Cited by 7 publications

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Temozolomide and interferon alpha2b in metastatic melanoma stage IV

Temozolomide and interferon alpha2b in metastatic melanoma stage IV

Strong inhibition of Ewing tumor xenograft growth by combination of human interferon-alpha or interferon-beta with ifosfamide

Cytotoxicity, DNA Damage, and Apoptosis Induced by New Fotemustine Analogs on Human Melanoma Cells in Relation to O⁶-Methylguanine DNA-Methyltransferase Expression

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Cisplatin, dacarbazine, and fotemustine plus interferon α in patients with advanced malignant melanoma

Cited by 7 publications

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Temozolomide and interferon alpha2b in metastatic melanoma stage IV

Temozolomide and interferon alpha2b in metastatic melanoma stage IV

Strong inhibition of Ewing tumor xenograft growth by combination of human interferon-alpha or interferon-beta with ifosfamide

Cytotoxicity, DNA Damage, and Apoptosis Induced by New Fotemustine Analogs on Human Melanoma Cells in Relation to O6-Methylguanine DNA-Methyltransferase Expression

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Cytotoxicity, DNA Damage, and Apoptosis Induced by New Fotemustine Analogs on Human Melanoma Cells in Relation to O⁶-Methylguanine DNA-Methyltransferase Expression