Gastrointestinal stromal tumor medical therapy
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Gastrointestinal stromal tumor Microchapters |
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Differentiating Gastrointestinal stromal tumor from other Diseases |
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Diagnosis |
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Treatment |
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Gastrointestinal stromal tumor medical therapy On the Web |
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American Roentgen Ray Society Images of Gastrointestinal stromal tumor medical therapy |
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Directions to Hospitals Treating Gastrointestinal stromal tumor |
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Risk calculators and risk factors for Gastrointestinal stromal tumor medical therapy |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Parminder Dhingra, M.D. [2]
Overview
The predominant therapy for gastrointestinal stromal tumor is surgical resection. Adjunctive chemotherapy/tyrosine Kinase Inhibitor therapy may be required.
Medical Therapy
- Laparoscopic surgical resection is the first-line treatment for primary and localized GIST. However, with advanced disease where surgery is not an option or unresectable lesions, patients are treated with chemotherapy.
- Around 95 % patients with GIST stain positive for CD117 and 5-10% have PDGFRA mutation and therefore treated with agents acting against CD117 and PDGFRA.
- Medical therapy is also given as part of pre and post-operative care to reduce risk of morbidity associated with surgical resection of GIST.
- Pre and post operative fluid resuscitation and transfusion (ringer lactate). Urinary Foley catheter to monitor fluid output
- Diet and nutrition: Specific peri-operative diet and nutrition (multivitamin and mineral supplements) may given either through a Ryle's tube or a peripheral/central line f
- Antibiotics cover: Patients with signs and symptoms of bowel perforation or infarction should be treated with intravenous antibiotic prophylaxis to prevent surgical wound infection and sepsis.
- Pain and deep venous thrombosis prophylaxis: Appropriate pain control (NSAID or morphine) and prophylaxis for DVT (heparin) may be given as a precautionary therapy in patients complaining of pain or breathlessness.
Treatment Option Overview for GIST
- Surgical Therapy
- Chemotherapy
- Tyrosine Kinase Inhibitor Therapy
Chemotherapy
- The advent of molecular genetics has drastically changed the outlook of patients with GIST.
- The use of tyrosine kinase inhibitors is now the primary medical treatment for patients with GIST.
- Prior to this, conventional chemotherapy were not effective in treating patients with GIST.
- Cells with MRP1 (multidrug resistance protein-1) and MDR-1 (multidrug resistance-1) gene produce P-glycoprotein that led to increased expression of cellular efflux pumps and prevented conventional chemotherapy agents to attain appropriate therapeutic levels.
Tyrosine Kinase Inhibitor Therapy
- Imatinib is a selective tyrosine kinase inhibitor effective against KIT, PDGFRA, and chronic myelogenous leukemia specific BCR-ABL protein.
- The tyrosine kinase inhibitor TKI imatinib mesylate is used as the first-line treatment for unresectable lesions (such as large primary GIST, metastatic or recurrent GIST).
- Surgery is associated with greater morbidity and mortality in patients with unresectable lesions.
- The benefit of TKI is largely evident from the fact that median survival rates have gone from less than 2 years to more than 5 years with the use of imatinib therapy.
- Recent studies also recommend the use of imatinib to decrease the recurrence rate in patients undergoing resection for primary GIST.
- Imatinib is also used to shrink tumor prior to surgery.
- 1.1 Tyrosine kinase inhibitor (TKI)
- 1.1.1 Unresectable lesions such as large primary GIST, metastatic or recurrent GIST.
- Preferred regimen (1): Imatinib 400 mg to 800 mg PO q24h
- Note (1):For unresectable lesions the treatment is usually life long.
- Note (2):Use of 800 mg daily dose has been observed with significant improvement in patients with KIT exon 9 mutation.
- Note (3):Patients resistant to 400 mg imatinib should have their dose increased to 800 mg PO q24h.
- Alternative regimen (1): Sunitinib 50 mg PO q24h
- Note (1):Sunitinib is given in 6 weeks cycle (with intake for 4 weeks and abstinence for 2 weeks).
- Note (2):Sunitinib has both antiangiogenic and anti-tumor effects.
- 1.1.2 Adjuvant therapy after resection
- Preferred regimen (1): Imatinib 400 mg PO q24h
- Note (1):For Adjuvant therapy after resection the recommended duration of treatment is 3 years.
Drug side effects
Common side effects of imatinib therapy include:
- Fluid retention (especially periorbital edema or peripheral edema; occasionally pleural effusion or ascites)
- Diarrhea
- Nausea
- Fatigue
- Muscle cramps
- Abdominal pain
- Rash
- Mild (macrocytic) anemia
Common side effects associated with sunitinib therapy include the following:[22,36]
- Fatigue
- Nausea and vomiting
- Anemia
- Neutropenia
- Diarrhea
- Abdominal pain
- Mucositis
- Anorexia
- Skin or hair discoloration
- Hypothyroidism (thyroid function monitoring with TSH is generally recommended to detect subclinical hypothyroidism)