Sarcoma drugs pazopanib, trabectedin, and eribulin

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What is sarcoma?

Sarcoma is a rare connective tissue tumor, so sarcoma can invade any part of our body. These tumors include liposarcoma, neurosarcoma, osteosarcoma, tendon sarcoma, muscle and skin sarcoma. They account for approximately 1% of all adult cancers and approximately 15% of childhood tumors. In addition to the widespread existence of potentially major sites and rare locations, there are more than 80 tumors with very mixed components with different histological subtypes. Sarcoma is a type of cancer. Sarcoma—Malignant tumor formed by cancellous bone, cartilage, fat, muscle, blood vessels, and tissue.

Three of these factors make the treatment of sarcoma very challenging. Therefore, it is very important for sarcoma patients to be treated by an experienced multidisciplinary team. The team needs to include surgeons, pathologists, radiologists, oncologists, specialist nurses, physical therapists and pharmacists. .

Diagnosis of sarcoma

In order to confirm the diagnosis, biopsy is needed to confirm the presence and specific subtype of sarcoma. Because these tumors are very rare and mixed, it is vital that an experienced pathologist examine biopsy samples. The initial diagnostic radiation tests included CT scans and MRI scans to determine the location and type of sarcoma.

Treatment of sarcoma

The mainstream treatment for localized sarcoma includes complete surgery combined with radiotherapy or no radiotherapy. The need for an experienced surgeon to perform the operation is very important, because the implementation of improper surgery may have an impact on the treatment outcome.

A large number of randomized clinical trials have confirmed that preoperative or postoperative radiotherapy has obvious benefits for sarcoma of the hand and foot and chest wall sarcoma. A recent international randomized clinical trial evaluated the role of preoperative radiotherapy in the treatment of retroperitoneal sarcoma.

In specific sarcoma subtype weeks, multi-agent chemotherapy is an important part of treatment management; these subtypes include Ewing’s sarcoma, osteosarcoma, and rhabdomyosarcoma. The introduction of these subtypes of multi-agent chemotherapy and limb salvage surgery has become a great success in the field of cancer treatment in the past 40 years.

Prognosis of sarcoma

Unfortunately, despite the use of optimal treatment for complete surgical resection, approximately 50% of patients with intermediate / advanced sarcoma develop relapsed / metastatic tumors. Metastasis usually spreads through blood vessels, and the lungs are the most common place for metastatic disease.

The prognostic results of patients with metastatic sarcoma are generally poor in the past, and there are few treatment options. However, recent data indicate that the median overall survival of patients with metastatic soft tissue sarcoma has increased from approximately 12 months to the current 18 months. There are now more available systemic treatment options for patients with metastatic sarcoma.

For patients with slow-growing histological subtypes, the monitoring of small / asymptomatic metastatic lesions is an option. Surgical resection is considered when the patient has a separate metastatic lesion, especially when the lesion is in the lungs. Other local treatment strategies may also be considered including radiotherapy, radiofrequency ablation and embolization.

The decision to treat metastatic lesions can be very complicated, and we emphasize again that this requires an experienced multidisciplinary team. For most patients with metastatic sarcoma, the main treatment depends on systemic treatment, mainly chemotherapy.

Targeted therapy in sarcoma

Targeted therapy drugs have been introduced in the subtype of soft tissue sarcoma called gastrointestinal stromal tumor (GIST), which has become an example of targeted therapy for solid tumors. Most gastrointestinal stromal tumors (GIST) have KIT and PDGFRA gene mutation characteristics. Due to the introduction of these tyrosine kinase inhibitors, the prognosis of patients with metastatic gastrointestinal stromal tumors (GIST) has been greatly improved.

In addition, imatinib has been approved as a treatment for high-risk tumors after resection. Imatinib has also been successfully used in the treatment of other sarcoma subtypes (called dermatofibrosarcoma protuberances (DFSP)).

Doxorubicin can be used alone or in combination with ifosfamide is still the standard first-line treatment for metastatic soft tissue sarcoma. In the past few years, the results of three international phase III clinical trials have been published or published.

The first clinical trial randomly selected patients to receive doxorubicin or doxorubicin and ifosfamide. This clinical trial reported no difference in overall survival rates for both arms, but patients on combination therapy had significantly longer progression-free survival and significantly higher response rates.

The second clinical trial randomly selected patients to receive doxorubicin and ifosfamide analogs (palifosfamide) or doxorubicin plus placebo. This clinical trial showed that the test results of the two arms were not significantly different. The third clinical trial randomized patients to receive a single dose of doxorubicin or gemcitabine / docetaxel. No significant difference in results was observed between these two arms.

In addition, a randomized clinical trial compared gemcitabine / docetaxel and gemcitabine monotherapy to establish an effective rescue schedule especially for the treatment of leiomyosarcoma and undifferentiated polymorphic sarcoma.

In 2007, marine-derived compound trabectedin was approved for use in the European Union. The approval was based on the results of two different timetables for the drug in a randomized phase II clinical trial. Subsequently, a phase III clinical trial showed that patients with advanced / metastatic liposarcoma and leiomyosarcoma were randomized to receive trabectedin or diazolid (the patients received Huihuan antitumor drugs and one other antitumor treatment before enrollment).

This clinical trial showed that patients who received trabectedin showed significantly longer progression-free survival than those who received diazolid. This led to the approval of the use of trabectedin by the US Food and Drug Administration in November 2015.

The oral tyrosine kinase inhibitor pazotinib has been approved based on the results of a randomized clinical trial of patients with soft tissue sarcoma receiving pazotinib or placebo. This clinical trial showed that the pazotinib group had a significant improvement in progression-free survival, but there was no significant difference in overall survival.

In 2016, the marine extract microtubule inhibitor eribulin was approved by the US Food and Drug Administration for the treatment of advanced liposarcoma. The approval is based on a randomized clinical trial of patients with stage III advanced / metastatic liposarcoma and leiomyosarcoma receiving eribulin or dacrabzine. This clinical trial showed that the eribulin arm has a significantly longer overall survival time than the dacarbzaine arm.

Conclusion

In conclusion, sarcomas are a group of rare cancers with a mixture of ingredients, and they face huge challenges in treatment and drug development. The introduction of tyrosine kinases in the treatment of gastrointestinal stromal tumors (GIST) is already an example in the targeted treatment of solid tumors.

In addition, in the past few years, some new systemic therapeutic agents have been added to the available options for the treatment of advanced sarcoma, including pazopanib, trabectedin, and eribulin. The international cooperation between a wider range of clinical researchers and basic scientists has continually promoted the advancement of hybrid cancer treatment methods of these ingredients.

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