Gastrointestinal stromal tumor medical therapy

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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 therefore treated with agents acting against CD117.
• 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. 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 which leads to increased cellular efflux pumps that prevented conventional chemotherapy agents to attain appropriate therapeutic levels.

Tyrosine Kinase Inhibitor Therapy

• The tyrosine kinase inhibitor TKI imatinib mesylate is used as the first-line treatment for unresectable lesions.

Oral: 400 mg once daily; may be increased up to 800 mg daily (400 mg twice daily), if tolerated, for disease progression. NOTE:Use of 800 mg daily dose has been observed with significant improvement in patients with KIT exon 9 mutation.

• • 1.1 Tyrosine kinase inhibitor TKI
    • 1.1.1 Adult
      • Preferred regimen (1): Imatinib 400 mg to 800 mg PO q24h

NOTE:Use of 800 mg daily dose has been observed with significant improvement in patients with KIT exon 9 mutation.

• • Unresectable lesions include large primary GIST, metastatic or recurrent GIST.
  • Surgery is associated with greater morbidity and mortality in patients with unresectable lesions.
• The use 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 b recommend the use of imatinib to decrease the recurrence rate in patients undergoing resection for primary GIST. (Oral: 400 mg once daily; recommended treatment duration: 3 years)
• Patients of GIST are generally treated with lifelong imatinib therapy.

• Imatinib is a selective tyrosine kinase inhibitor effective against KIT, PDGFRA, and chronic myelogenous leukemia specific BCR-ABL protein.
• Imatinib is also used to shrink tumor prior to surgery.

Drug side effects

The most common toxicities associated with imatinib therapy, all of which may improve with prolonged treatment, include the following:

• Fluid retention (especially periorbital edema or peripheral edema; occasionally pleural effusion or ascites)
• Diarrhea
• Nausea (may be diminished if taken with food)
• Fatigue
• Muscle cramps
• Abdominal pain
• Rash
• Mild (macrocytic) anemia

Treatment with sunitinib may be considered for patients with life-threatening side effects from imatinib that cannot be managed by maximum supportive care.[4] 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)

References

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