A phase II trial of bevacizumab with dacarbazine and daily low-dose interferon-α2a as first line treatment in metastatic melanoma

Pia P. Vihinen, Micaela Hernberg, Meri-Sisko Vuoristo, Kristiina Tyynelä, Marjut Laukka, Johan Lundin, Johanna Ivaska, Seppo Pyrhönen

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Abstract

Metastatic melanomas are hypervascular tumours with poor prognosis. We hypothesized that treatment of metastatic melanoma with a combination of bevacizumab, a monoclonal antibody against vascular endothelial growth factor, dacarbazine (DTIC) and low-dose interferon α-2a (IFN-α2a) might lead to a synergistic inhibition of angiogenesis and regression of tumours. Patients with metastatic melanoma were treated with bevacizumab (5 mg/kg every 2 weeks), DTIC (200 mg/m2 days 1–5 every 4 weeks) and IFN-α2a (three MIU subcutaneously daily from day 15 onwards). Patients exhibiting response or stable disease after 6 months were treated with bevacizumab±IFN-α2a until disease progression. The primary study objectives were progression-free survival (PFS), overall survival and safety. Twenty-six patients were accrued. Response rate was 23% (two complete responses, four partial responses), and six patients showed stable disease. The median PFS for all patients was 2.3 months and for responders 8.1 months. The median overall survival for all patients was 11.5 months. Four life-threatening adverse events were seen: two pulmonary thromboembolisms, an intracerebral haemorrhage, and one grade 4 hypertension. One of the pulmonary emboli and the intracerebral haemorrhage were observed ≥3 months after the last bevacizumab–DTIC dose. Serum matrix metalloproteinase-9 and vascular endothelial growth factor levels changed during therapy. There was a trend towards favourable PFS among patients with only minimal or moderate change in these marker expression levels. The present regimen was active in this patient group but was also associated with remarkable vascular events.
Original languageEnglish
Pages (from-to)318-325
JournalMelanoma Research
Volume20
Issue number4
DOIs
Publication statusPublished - 2010
MoE publication typeA1 Journal article-refereed

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Dacarbazine
Interferons
Melanoma
Disease-Free Survival
Cerebral Hemorrhage
Therapeutics
Vascular Endothelial Growth Factor A
Survival
Bevacizumab
Matrix Metalloproteinase 9
Embolism
Pulmonary Embolism
Blood Vessels
Disease Progression
Neoplasms
Monoclonal Antibodies
Hypertension
Safety
Lung
Serum

Cite this

Vihinen, P. P., Hernberg, M., Vuoristo, M-S., Tyynelä, K., Laukka, M., Lundin, J., ... Pyrhönen, S. (2010). A phase II trial of bevacizumab with dacarbazine and daily low-dose interferon-α2a as first line treatment in metastatic melanoma. Melanoma Research, 20(4), 318-325. https://doi.org/10.1097/CMR.0b013e3283390365
Vihinen, Pia P. ; Hernberg, Micaela ; Vuoristo, Meri-Sisko ; Tyynelä, Kristiina ; Laukka, Marjut ; Lundin, Johan ; Ivaska, Johanna ; Pyrhönen, Seppo. / A phase II trial of bevacizumab with dacarbazine and daily low-dose interferon-α2a as first line treatment in metastatic melanoma. In: Melanoma Research. 2010 ; Vol. 20, No. 4. pp. 318-325.
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title = "A phase II trial of bevacizumab with dacarbazine and daily low-dose interferon-α2a as first line treatment in metastatic melanoma",
abstract = "Metastatic melanomas are hypervascular tumours with poor prognosis. We hypothesized that treatment of metastatic melanoma with a combination of bevacizumab, a monoclonal antibody against vascular endothelial growth factor, dacarbazine (DTIC) and low-dose interferon α-2a (IFN-α2a) might lead to a synergistic inhibition of angiogenesis and regression of tumours. Patients with metastatic melanoma were treated with bevacizumab (5 mg/kg every 2 weeks), DTIC (200 mg/m2 days 1–5 every 4 weeks) and IFN-α2a (three MIU subcutaneously daily from day 15 onwards). Patients exhibiting response or stable disease after 6 months were treated with bevacizumab±IFN-α2a until disease progression. The primary study objectives were progression-free survival (PFS), overall survival and safety. Twenty-six patients were accrued. Response rate was 23{\%} (two complete responses, four partial responses), and six patients showed stable disease. The median PFS for all patients was 2.3 months and for responders 8.1 months. The median overall survival for all patients was 11.5 months. Four life-threatening adverse events were seen: two pulmonary thromboembolisms, an intracerebral haemorrhage, and one grade 4 hypertension. One of the pulmonary emboli and the intracerebral haemorrhage were observed ≥3 months after the last bevacizumab–DTIC dose. Serum matrix metalloproteinase-9 and vascular endothelial growth factor levels changed during therapy. There was a trend towards favourable PFS among patients with only minimal or moderate change in these marker expression levels. The present regimen was active in this patient group but was also associated with remarkable vascular events.",
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Vihinen, PP, Hernberg, M, Vuoristo, M-S, Tyynelä, K, Laukka, M, Lundin, J, Ivaska, J & Pyrhönen, S 2010, 'A phase II trial of bevacizumab with dacarbazine and daily low-dose interferon-α2a as first line treatment in metastatic melanoma', Melanoma Research, vol. 20, no. 4, pp. 318-325. https://doi.org/10.1097/CMR.0b013e3283390365

A phase II trial of bevacizumab with dacarbazine and daily low-dose interferon-α2a as first line treatment in metastatic melanoma. / Vihinen, Pia P.; Hernberg, Micaela; Vuoristo, Meri-Sisko; Tyynelä, Kristiina; Laukka, Marjut; Lundin, Johan; Ivaska, Johanna; Pyrhönen, Seppo.

In: Melanoma Research, Vol. 20, No. 4, 2010, p. 318-325.

Research output: Contribution to journalArticleScientificpeer-review

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T1 - A phase II trial of bevacizumab with dacarbazine and daily low-dose interferon-α2a as first line treatment in metastatic melanoma

AU - Vihinen, Pia P.

AU - Hernberg, Micaela

AU - Vuoristo, Meri-Sisko

AU - Tyynelä, Kristiina

AU - Laukka, Marjut

AU - Lundin, Johan

AU - Ivaska, Johanna

AU - Pyrhönen, Seppo

PY - 2010

Y1 - 2010

N2 - Metastatic melanomas are hypervascular tumours with poor prognosis. We hypothesized that treatment of metastatic melanoma with a combination of bevacizumab, a monoclonal antibody against vascular endothelial growth factor, dacarbazine (DTIC) and low-dose interferon α-2a (IFN-α2a) might lead to a synergistic inhibition of angiogenesis and regression of tumours. Patients with metastatic melanoma were treated with bevacizumab (5 mg/kg every 2 weeks), DTIC (200 mg/m2 days 1–5 every 4 weeks) and IFN-α2a (three MIU subcutaneously daily from day 15 onwards). Patients exhibiting response or stable disease after 6 months were treated with bevacizumab±IFN-α2a until disease progression. The primary study objectives were progression-free survival (PFS), overall survival and safety. Twenty-six patients were accrued. Response rate was 23% (two complete responses, four partial responses), and six patients showed stable disease. The median PFS for all patients was 2.3 months and for responders 8.1 months. The median overall survival for all patients was 11.5 months. Four life-threatening adverse events were seen: two pulmonary thromboembolisms, an intracerebral haemorrhage, and one grade 4 hypertension. One of the pulmonary emboli and the intracerebral haemorrhage were observed ≥3 months after the last bevacizumab–DTIC dose. Serum matrix metalloproteinase-9 and vascular endothelial growth factor levels changed during therapy. There was a trend towards favourable PFS among patients with only minimal or moderate change in these marker expression levels. The present regimen was active in this patient group but was also associated with remarkable vascular events.

AB - Metastatic melanomas are hypervascular tumours with poor prognosis. We hypothesized that treatment of metastatic melanoma with a combination of bevacizumab, a monoclonal antibody against vascular endothelial growth factor, dacarbazine (DTIC) and low-dose interferon α-2a (IFN-α2a) might lead to a synergistic inhibition of angiogenesis and regression of tumours. Patients with metastatic melanoma were treated with bevacizumab (5 mg/kg every 2 weeks), DTIC (200 mg/m2 days 1–5 every 4 weeks) and IFN-α2a (three MIU subcutaneously daily from day 15 onwards). Patients exhibiting response or stable disease after 6 months were treated with bevacizumab±IFN-α2a until disease progression. The primary study objectives were progression-free survival (PFS), overall survival and safety. Twenty-six patients were accrued. Response rate was 23% (two complete responses, four partial responses), and six patients showed stable disease. The median PFS for all patients was 2.3 months and for responders 8.1 months. The median overall survival for all patients was 11.5 months. Four life-threatening adverse events were seen: two pulmonary thromboembolisms, an intracerebral haemorrhage, and one grade 4 hypertension. One of the pulmonary emboli and the intracerebral haemorrhage were observed ≥3 months after the last bevacizumab–DTIC dose. Serum matrix metalloproteinase-9 and vascular endothelial growth factor levels changed during therapy. There was a trend towards favourable PFS among patients with only minimal or moderate change in these marker expression levels. The present regimen was active in this patient group but was also associated with remarkable vascular events.

U2 - 10.1097/CMR.0b013e3283390365

DO - 10.1097/CMR.0b013e3283390365

M3 - Article

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