Paclitaxel in patients with advanced angiosarcomas of soft tissue: A retrospective study of the EORTC soft tissue and bone sarcoma group
Introduction
Angiosarcomas of soft tissue represent a heterogenous subgroup of soft tissue and visceral sarcomas, showing histological differentiation of endothelial cell lineage. Angiosarcomas can occur everywhere in the body, but are most often found in the head and neck, followed by extremities and trunk.1 Predisposing factors include chronic lymphedema (Stewart–Treves syndrome) and radiation,2 furthermore genetic predisposition may play a role in the development of angiosarcoma after radiation therapy.3 Risk factors for poor prognosis are old age, retroperitoneal location, size and elevated Ki-67 immunoreactivity.4, 5, 6, 7
As for other soft tissue sarcoma complete excision is the treatment of choice, but in most cases, due to localisation in face, scalp, heart or liver complete radical resection is not possible. Therefore, surgery is often combined with adjuvant radiation therapy, chemotherapy or combination of these modalities,8 albeit that there is no scientific justification for the latter. Radiation after resection is correlated with improved outcome.9 Although no phase II trials were performed specifically in angiosarcomas, doxorubicin and ifosfamide are generally considered to be the most active chemotherapeutic agents.
Paclitaxel is an anti-tumour drug with proven activity in solid cancers such as ovarian-, breast- and lungcancer, but limited activity in advanced soft tissue sarcomas.10, 11 The main mechanism of action is the inhibition of normal mitotic spindle formation by tight binding to beta tubulin, resulting in a blockage of microtubules depolymerisation and mitotic arrest in the late G2/M phase.12 Additionally, paclitaxel exhibits strong antiangiogenic inhibitory activity.13, 14 In small retrospective series, paclitaxel was found to have a promising efficacy in angiosarcomas.15, 16 To confirm these observations, we performed a retrospective analysis of angiosarcomas treated with single agent paclitaxel in centres of the EORTC soft tissue and bone sarcoma group.
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Patients and treatment
Patients with histologically confirmed angiosarcoma were retrospectively identified in 10 centres of the EORTC soft tissue and bone sarcoma group. Treatment was performed between 1996 and 2005. The diagnosis of angiosarcomas was confirmed by histopathological review at the treating centre. Paclitaxel was given as a 3 h infusion either at a dose between 135 and 175 mg/m2 in a 3 weekly schedule (n = 21), or at a dose of 75–100 mg/m2 (n = 11), given weekly. Tumour assessment was performed using WHO or
Results
Characteristics of the 32 patients are listed in Table 1. There were 15 females and 17 males. The mean age was 60, 4 years (range, 25–91). Angiosarcomas were located in scalp and face in 8 patients (25%) and at other primary sites in 24 patients (75%). All patients had intermediate (n = 13) or high grade (n = 19) primary tumours. Thirteen (40%) patients had been pretreated with doxorubicin-based first-line-chemotherapy regimens – three of them (9%) also had second-line chemotherapy with ifosfamide.
Discussion
Angiosarcomas of soft tissue are rare, accounting for 1% of all sarcomas. Clinical features vary depending on the anatomic location. Patients with face and scalp angiosarcomas demonstrate longer overall survival than the patients with angiosarcomas at the visceral sites. Secondary angiosarcomas after radiation therapy are associated with poor prognosis.17 The standard treatment in localized disease is surgery, but due to the location in face and scalp radical resection without mutilation is
Conflict of interest statement
None declared.
Acknowledgements
Ferreira M, Instituto Portugues de Oncologia, Lisboa De Vries E, Groningen University Hospital Kouroussis C, University Heraklion
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