eMedicine Specialties > Oncology > Sarcomas of Soft Tissue and Bone
Angiosarcoma: Treatment & Medication
Updated: Jan 9, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
- Adjuvant therapy in soft tissue angiosarcoma7,16
- Multiple randomized studies using doxorubicin-based chemotherapy fail to show a survival benefit from neoadjuvant chemotherapy, although metaanalysis suggests improved local control and disease-free survival with chemotherapy, but no survival advantage.
- Because of the poor results (40-50% with the most active regimens) and the significant toxicity, specialists reserve preoperative chemotherapy for patients with high-grade lesions. Continue using the regimen for those patients who respond with tumor shrinkage after 2-3 courses of multiagent chemotherapy after tumor resection.
- Offer patients with unresponsive tumors different treatment regimens. Response to neoadjuvant chemotherapy can be observed, but it does not always correlate with radiographic response.
- Radiotherapy: The use of irradiation in conjunction with surgery continues to evolve and results in 80% of local control and excellent functional and cosmetic outcome. However, consider that 50% of angiosarcomas have distant metastasis, and irradiation does not improve survival. Better definition of the extent of the disease with the use of MRI helps to further delineate the radiotherapy fields and decrease long-term morbidity. Intraoperative radiation, brachytherapy, or more external beam therapy can complement preoperative external beam radiotherapy. The advantages and disadvantages are as follows:
- Advantages of preoperative radiation - Optimization for surgery, smaller volume of external beam fields, less hypoxic tissue, potential to reduce the chance of intraoperative implantation, and potential improvement in local control in advanced tumors
- Disadvantages - Higher wound complication rate may delay surgery (1 wk of healing per 10 Gy of radiation delivered)
- Surgery combined with radiotherapy appears to afford the best local control rates.5
- Adjuvant therapy in bone angiosarcoma
- Evidence of multicentricity must be sought before making any decision regarding therapy. Some patients present with lesions affecting 45 different bones. In these cases, consider neoadjuvant chemotherapy.
- A chemotherapeutic regimen common for sarcomatous tumors can be administered (ifosfamide and doxorubicin used together or sequentially). If clinical or radiographic improvement is not observed, consider a second regimen with cyclophosphamide, etoposide, and cisplatin. Gemcitabine may be effective as second line or third-line therapy.
- Adjuvant therapy in cutaneous angiosarcoma16
- The role of chemotherapy in cutaneous angiosarcoma has not yet been established, although for patients with metastasis or tumors deemed unresectable, doxorubicin (intraarterial or systemic) is indicated.
- Recent studies present paclitaxel as a single agent with substantial activity against angiosarcoma of the scalp or face, even in patients previously treated with chemotherapy or radiation therapy.17 Further investigation is warranted to define the optimal treatment dose and schedule.
- The best outcomes are reported with surgery followed by radiotherapy.
Surgical Care
- Angiosarcoma of the soft tissue, retroperitoneum, and abdomen2
- Target obtaining wide surgical margins, with at least 2 cm of unaffected tissue surrounding the tumor. The resection should include skin when applicable and the soft tissue around the angiosarcoma. Include biopsy sites, including the biopsy tract, en bloc with the specimen.
- Resection of large lesions can be extremely difficult and sometimes requires amputation for local control; however, local control does not prevent distant relapse.
- Free surgical margins sometimes have anatomic constraints, especially in retroperitoneal tumors.
- Angiosarcoma of bone
- Surgical resection and radiation therapy are the standard treatment for localized disease.
- Low-grade lesions lead to similar benefits with either technique.
- Treat high-grade lesions as malignant bone neoplasms, with a combination of radical en bloc excision followed by radiotherapy and/or chemotherapy.
- The number of lesions in a limb may render limb salvage impossible, and amputation may be indicated.
- Cutaneous angiosarcoma10
- Surgical treatment is contraindicated in tumors extending into vital structures, in those of massive size, or in those with multicentricity.
- The lesion may be solitary or multicentric and frequently extends laterally throughout the dermis, making gross assessment of surgical margins difficult and necessitating multiple biopsies of the surrounding tissues.
- In the primary treatment of angiosarcomas of the scalp, recognizing the horizontal and vertical extensions of the tumor is essential, which can only be discerned by microscopic examination of all the margins of the resected specimen. The primary excision of the scalp should be full-thickness, including the pericranium and, if indicated, the outer table of the cranial vault. The margins should be wide (at least 5 cm) on all sides.
Medication
The goals of pharmacotherapy are to reduce morbidity, prevent complications, and eradicate the cancer.
Antineoplastic agents
Inhibit cell growth and proliferation.
Doxorubicin (Adriamycin)
A cytotoxic anthracycline antibiotic isolated from Streptomyces peucetius var. caesius. These drugs are structurally similar to tetracycline and interfere with DNA production by the cell. All cells can be affected, but rapidly producing cells are damaged. Active against many cancers and has been in use for decades. A clear orange-red powder or liquid only administered IV. Binds DNA and inhibits nucleic acid synthesis. Also a powerful iron chelator and iron-doxorubicin complex, induces production of free radicals that can destroy DNA and cancer cells.
Functional properties of a drug can be substantially affected by liposomal encapsulation. Liposomes used in different drug products can vary in their chemical and physical properties. These differences can substantially affect functional properties among liposomal drug products.
May continue treatment for as long as patient shows progress, shows no evidence of cardiotoxicity, and continues to tolerate treatment; PPE, stomatitis, or hematological toxicity may require doses to be delayed or reduced. Minimum of 4 courses recommended.
Adult
Doxorubicin HCL injection (Adriamycin): 60-75 mg/m2 IV as single dose, repeat q21d; alternatively, 20-30 mg/m2 IV qd for 3 d, repeat in 4 wk; or 20 mg/m2 qwk
Doxorubicin HCl liposome injection (Doxil): 50 mg/m2 (doxorubicin HCL equivalent) IV 1 mg/min, if tolerated, increase rate of infusion to complete administration over 1 h; repeat q4wk
Pediatric
35-75 mg/m2 IV as single dose q21d; or 20 mg/m2 qwk
Decreases digoxin plasma levels and renal excretion; allopurinol may enhance antitumor activity; toxicity increases with cyclophosphamide, mercaptopurine, and streptozocin; verapamil increases cell toxicity
Documented hypersensitivity; in severe CHF, if LVEF is <40%, therapy should not be instituted; preexisting myelosuppression; previous treatment with complete cumulative doses of other anthracyclines or anthracenediones
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Total dose should not exceed 400 mg/m2 in patients with previous or concomitant treatment (eg, cyclophosphamide, daunorubicin, radiation of cardiac region), otherwise do not exceed 550 mg/m2; irreversible cardiac toxicity may occur as total dosage approaches 550 mg/m2; extravasation results in severe local tissue necrosis
Ifosfamide (Ifex)
An alkylating agent. Inhibits DNA and protein synthesis and, thus, cell-proliferation by causing DNA cross-linking and denaturation of double helix.
Adult
1.8 g/m2/d IV for 5 d
Pediatric
Administer as in adults
Phenobarbital, phenytoin, chloral hydrate, and other drugs that interfere with cytochrome P-450 activity, may alter effects of ifosfamide
Documented hypersensitivity; depressed bone marrow function
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause hemorrhagic cystitis and severe myelosuppression; caution in renal function impairment or compromised bone marrow reserve
Gemcitabine (Gemzar)
Cytidine analog. Metabolized intracellularly to active nucleotide. Inhibits ribonucleotide reductase and competes with deoxycytidine triphosphate for incorporation into DNA. Cell-cycle specific for S phase. Indicated as first-line treatment for locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) pancreatic adenocarcinoma. Indicated for patients previously treated with 5-FU.
Adult
Cycle 1: 1000 mg/m2 IV infused over 30 min qwk for up to 7 wk (or until toxicity requires lower dose or holding the dose); rest for 1 wk, then resume with subsequent cycles
Subsequent cycles: 1000 mg/m2 IV infused over 30 min qwk for 3 consecutive weeks out of every 4 wk
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause myelosuppression (particularly thrombocytopenia); toxicities include flu like syndrome, LFT abnormality, maculopapular rash, pruritus, nausea, vomiting, dyspnea, hematuria, proteinuria, and hemolytic uremic syndrome; clearance reduced in women and elderly individuals
More on Angiosarcoma |
| Overview: Angiosarcoma |
| Differential Diagnoses & Workup: Angiosarcoma |
 Treatment & Medication: Angiosarcoma |
| Follow-up: Angiosarcoma |
| Multimedia: Angiosarcoma |
| References |
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References
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Further Reading
Keywords
angiosarcoma, hemangioendothelioma, lymphangioendothelioma, hemangiosarcoma, hemangioblastoma, lymphangiosarcoma, angioendothelioma, malignant angioma, malignant endothelioma, malignant neoplasm, soft tissue sarcoma, soft tissue angiosarcoma, angiosarcoma of the soft tissue, cutaneous angiosarcoma, angiosarcoma of the liver, breast angiosarcoma, angiosarcoma of the breast, bone angiosarcoma, angiosarcoma of the bone, head and neck angiosarcoma, visceral angiosarcoma, hepatic angiosarcoma, lung angiosarcoma, pulmonary angiosarcoma, heart angiosarcoma, cardiac angiosarcoma
