Introduction
Soft tissue sarcomas are a rare disease with many subtypes. It constitutes less than 1% of all
adult cancers. The main treatment is surgery. The tumor should be completely removed, leaving enough healthy tissue around it. In some patients, adjuvant
radiotherapy and chemotherapy may be applied in addition to surgery. Disseminated disease may develop over time in approximately half of the patients who are diagnosed at an early stage and treated curatively.
Systemic treatment comes to the fore in locally advanced or metastatic disease that is not suitable for surgery. The aim of systemic
treatment is to increase survival, reduce the tumor mass
and reduce the patient's complaints rather than definitive treatment of the disease. The future of soft tissue sarcomas, which is a heterogeneous group of diseases, and their response to chemotherapy can be quite different.
In the first series of metastatic disease, doxorubicin single agent treatment and in appropriate indications
ifosfamide (IMA regimen) remains the standard treatment approach.
Many soft tissue sarcoma subtypes are primarily resistant to chemotherapy.
With targeted treatments, positive results have begun to be obtained in chemorefractory sarcoma types
. Today, despite all these treatment alternatives, survival times in advanced stage disease are not sufficient.
Chemotherapy in metastatic soft tissue sarcomas
In the last 50 years, many treatments have been used in the treatment of metastatic soft tissue sarcomas. Different chemotherapy agents
were tried, of which doxorubicin, ifosfamide, gemcitabine and dacarbazine were the main effective agents
. These drugs can be used alone or in combination with other drugs
Monotherapy
Anthracyclines (especially doxorubicin) are used primarily for metastatic soft tissue sarcomas
They are the most basic agents of stepwise treatment. Many studies have been conducted to evaluate the single-agent effectiveness of doxorubicin and compare it with other agents. In the light of current studies, doxorubicin is accepted as the standard agent in the first series of metastatic treatment
. The effective dose determined in studies is >60 mg/m2 (usually 75 mg/m g/m 2 ) Application every 3 weeks
. Treatment duration is limited to 6 cycles due to cumulative cardiotoxicity.
In addition to the effectiveness of doxorubicin, due to the dose-limiting effect of its cumulative toxicity
other anthracycline group agents are also used in the treatment of metastatic soft tissue sarcomas
Their effectiveness has been tested. Studies conducted with epirubicin and pegylated liposomal doxorubicin (Caelyx) reported similar effectiveness and less side effect rates.
Ifosfamide has been shown to be effective in the treatment of metastatic soft tissue sarcomas.
is one of the agents. Although the results obtained in studies with high doses instead of standard doses are similar, they appear to be slightly more successful. However, it is recommended to be used in the second step after doxorubicin, not in the first series.
Many agents such as gemcitabine, vinorelbine, methotrexate, temozolomide, cisplatin, carboplatin and dacarbazine
It has been evaluated in the treatment of metastatic soft tissue sarcomas. All of these
agents have been found to have limited single agent activity. Although the single agent efficacy of gemcitabine is low
, it is effective in combination regimens, especially in combination with docetaxel, vinorelbine and dacarbazine
. Although the studies conducted with the new agents trabectedin and eribulin are promising, they are far from producing revolutionary results in the treatment of sarcoma.
Combination Chemotherapy
Metastatic Although there are studies investigating the question of whether single agent or combined treatment should be given in soft tissue sarcomas, no significant survival advantage has been demonstrated. In studies comparing the effectiveness of single agent
doxorubicin and doxorubicin + ifosfamide combination (IMA)
Although survivals are similar, response
rates are higher in the combination arm. As expected, side effects are also more common. Combination therapy is preferred in patient groups who are young,
who have good performance status, who have symptoms due to mass effect, and who have the possibility of recovery with the use of additional treatment methods such as surgery and radiotherapy
It is thought that it should be considered.
Single agent gemcitabine is effective against metastatic soft tissue sagging. It has limited effectiveness
in the treatment of tumors. The most clinically studied and shown to be effective is its combination with docetaxel
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