eMedicine Specialties > Pediatrics: General Medicine > Allergy & Immunology
Thymoma: Treatment & Medication
Updated: Dec 12, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
- Postoperative radiotherapy has been used for invasive thymoma and incompletely resected thymoma.
- Commonly, radiotherapy has treated T tumors demonstrated to be unresectable on CT scan or with supraclavicular extension.
- Primary radiotherapy in unresectable stage III or stage IVa disease has controlled local disease with a 5-year survival rate of 45-50%.2
- Combination chemotherapy using cisplatin has been reported to have a response rating of 70-80%. Doxorubicin, vincristine, and cyclophosphamide have been used in combination chemotherapy.
- The acquired immunodeficiency associated with thymoma should be treated with monthly replacement immunoglobulin (Ig) therapy. Replacement Igs may be intravenously or subcutaneously administered. Doses of intravenous Igs should be 300-400 mg/kg every 3 weeks or 400-500 mg/kg every 4 weeks with dose adjustment to maintain trough IgG levels above 500-600 mg/dL. In addition, prophylactic antibiotics may be required in addition to Ig replacement therapy to prevent bacterial infections in immunodeficient patients. Aggressive and long-term antibiosis is often required to treat bacterial infections in these patients.21
Surgical Care
- Because thymoma is usually well encapsulated and characterized by local spread, thymectomy can be curative in the early stages.
- Encapsulated (stage I) tumors can usually be completely excised, and the local relapse rate is less than 5%. The relapse rate increases in more invasive stages.
- Surgery can be challenging because of the tendency of the tumor to surround blood vessels, bronchi, and other mediastinal structures. Excessive bleeding can complicate thymectomy of large tumors that have become vascular or lacunar.
- Tumor recurrence can occur even after complete resection.29
- Eighty-five percent of patients with myasthenia gravis (MG) have some histologic abnormality of the thymus.
- Thymectomy is considered a routine treatment for MG. Reportedly, resection of the thymoma is associated with improvement in weakness in 25% of patients, and almost one half of patients without thymoma improve after thymectomy.13
- A recent study of 153 patients by Werneck et al compared thymectomy with conservative treatment groups in paired patients at similar stages and found no statistical difference between the conservative treatment and thymectomy groups.30
- Thymectomy is believed to improve muscle weakness in 25% of individuals with MG and thymoma and in 50% of patients with MG without thymoma.
- Thymectomy results in resolution of red cell aplasia in 30% of persons with this disorder.
- The acquired immunodeficiency phenotype does not improve after thymectomy, and, in some persons, immunodeficiency has occurred years after resection of a thymoma.31
Medication
Although the treatment of choice for thymoma is surgical resection, chemotherapy and/or radiation has been shown to decrease the rate of tumor recurrence when complete excision is not possible. Radiation therapy alone in patients with invasive or bulky tumors has demonstrated a 50-70% recurrence rate.
The use of surgery as a sole treatment heavily depends on the stage of the thymoma, and complete resection has been shown to be a significant predictor of 5-year survival in Masoaka stages I, II, and III.32
Various treatment protocols have been used.
Fornasiero and colleagues studied 32 patients with stage III and IV thymomas treated with cisplatin, doxorubicin, vincristine, and cyclophosphamide; they reported a 91% radiologically defined response rate with 47% complete remission.33
Macchiarini's group demonstrated an 80% survival rate in 20 patients given preoperative chemotherapy with cisplatin, epirubicin, and etoposide; surgery for those whose condition responded to treatment; and subsequent postoperative radiation.34
Loehrer's group studied 26 adults with limited-stage unresectable thymoma who were administered cisplatin, doxorubicin, and cyclophosphamide, followed by radiation; the study demonstrated 5 complete responses, 11 partial responses, and a 5-year-survival rate of 52.5%.35
Venuta's group prospectively studied 65 patients who were undergoing surgical resection of stage I, II, and III thymomas.36 The patients were treated with adjuvant or neoadjuvant chemotherapy with cisplatin, epirubicin hydrochloride, and etoposide. The 8-year-survival rates for patients with stages I, II, III, and IV thymomas were 95%, 100%, 92%, and 68%, respectively.
Somatostatin analogue–based therapy is a more recent treatment modality and shows promise in the treatment of unresponsive thymomas. Palmieri reported the outcome of 17 patients with extensive advanced thymoma selected because of the significant uptake of indium-labeled octreotide, indicating the presence of somatostatin receptors.37
The patients had previously been treated with chemotherapy, and the thymomas were no longer responsive to conventional therapies. The patients received one of the somatostatin analogues plus prednisone. Octreotide (1.5 mg/d SC) was changed to the longer-acting lanreotide (30 mg IM q14d) if the shorter-acting preparation was well tolerated; the accompanying prednisone dose of 0.6 mg/kg/d usually was reduced after 3 months to 0.2 mg/kg/d. Of the 13 patients available for follow-up study after 25 months, 2 showed complete response, 5 showed partial response, and 6 had stable disease. One patient showed resolution of associated red cell aplasia.37
Treatment protocols
Macchiarini et al (1991)34
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Table
| Cisplatin | 75 mg/m2 on day 1 | 3 courses repeated q3wk |
| Epirubicin | 100 mg/m2 on day 1 | |
| Etoposide | 120 mg/m2 on days 1, 3, and 5 | |
| Surgery and radiation in patients with complete or partial response to chemotherapy | 4500 cGy if complete resection 6000 cGy if incomplete resection |
| Cisplatin | 75 mg/m2 on day 1 | 3 courses repeated q3wk |
| Epirubicin | 100 mg/m2 on day 1 | |
| Etoposide | 120 mg/m2 on days 1, 3, and 5 | |
| Surgery and radiation in patients with complete or partial response to chemotherapy | 4500 cGy if complete resection 6000 cGy if incomplete resection |
Loehrer et al (1997)35
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Table
| Cisplatin | 50 mg/m2 | 2-4 cycles q3wk |
| Doxorubicin | 50 mg/m2 | |
| Cyclophosphamide | 500 mg/m2 | |
| Followed by radiation | 54 Gy to the primary tumor and lymph nodes | |
| Cisplatin | 50 mg/m2 | 2-4 cycles q3wk |
| Doxorubicin | 50 mg/m2 | |
| Cyclophosphamide | 500 mg/m2 | |
| Followed by radiation | 54 Gy to the primary tumor and lymph nodes | |
Venuta et al (1997)36
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Table
| Cisplatin | 75-100 mg/m2 on day 1 | Repeated q3wk 3 times before surgery and 2 or 3 times after surgery |
| Epirubicin hydrochloride | 100 mg/m2 on day 1 | |
| Etoposide | 120 mg/m2 on days 1, 3, and 5 | |
| Postoperative radiation in patients with radical resection | 30 Gy | Delivered in 3 wk with 5 fractions per wk |
| Postoperative radiation in patients with incomplete resection | 50 Gy | Delivered in 5 wk with 5 fractions per wk |
| Cisplatin | 75-100 mg/m2 on day 1 | Repeated q3wk 3 times before surgery and 2 or 3 times after surgery |
| Epirubicin hydrochloride | 100 mg/m2 on day 1 | |
| Etoposide | 120 mg/m2 on days 1, 3, and 5 | |
| Postoperative radiation in patients with radical resection | 30 Gy | Delivered in 3 wk with 5 fractions per wk |
| Postoperative radiation in patients with incomplete resection | 50 Gy | Delivered in 5 wk with 5 fractions per wk |
Palmieri et al (1999)37
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Table
| Octreotide | 1.5 mg/d SC | In patients shown to have somatostatin receptors |
| Lanreotide | 30 mg/d SC q14d | Switch to this longer-acting somatostatin analogue or depot form of octreotide if short-acting octreotide is well tolerated |
| Prednisone | 0.6 mg/kg/d PO for 3 mo, then decreasing to 0.2 mg/kg |
| Octreotide | 1.5 mg/d SC | In patients shown to have somatostatin receptors |
| Lanreotide | 30 mg/d SC q14d | Switch to this longer-acting somatostatin analogue or depot form of octreotide if short-acting octreotide is well tolerated |
| Prednisone | 0.6 mg/kg/d PO for 3 mo, then decreasing to 0.2 mg/kg |
Antineoplastic agents
Combination chemotherapy using cisplatin is reported to have a response rate of 70-80%. Doxorubicin, vincristine, and cyclophosphamide have been used in combination chemotherapy.
Cisplatin (Platinol)
Inhibits DNA synthesis and, thus, cell proliferation by causing DNA cross-links and denaturation of the double helix.
Adult
Pediatric
50-100 mg/m2 IV repeated q3wk for 3-6 cycles
Increases toxicity of bleomycin and ethacrynic acid; aluminum reacts with cisplatin to form a black precipitate and gas (apparatus used to administer cisplatin must not contain aluminum); vaccination with live vaccines (eg, MMR) in immunosuppressed patients may result in severe or fatal infections; coadministration with other nephrotoxic drugs (eg, aminoglycosides, cyclosporine) may increase risk of nephrotoxicity
Documented hypersensitivity; preexisting renal insufficiency; myelosuppression; hearing impairment
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
To reduce risk of nephrotoxicity, administer adequate hydration before and 24 h after dosing; myelosuppression, ototoxicity, and nausea and vomiting may occur
Doxorubicin (Adriamycin, Rubex)
Inhibits topoisomerase II and produces free radicals, which may cause destruction of DNA. Combination of these 2 events can inhibit growth of neoplastic cells.
Adult
Pediatric
50 mg/m2 IV q3wk for 2-4 cycles
May decrease phenytoin and digoxin plasma levels; phenobarbital may decrease plasma levels of doxorubicin; cyclosporine may induce coma or seizures; mercaptopurine increases toxicity of doxorubicin; cyclophosphamide increases cardiac toxicity of doxorubicin; vaccination with live vaccines (eg, MMR) in immunosuppressed patients may result in severe or fatal infections
Documented hypersensitivity; severe heart failure; cardiomyopathy; impaired cardiac function; preexisting myelosuppression
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Irreversible cardiac toxicity and myelosuppression may occur; extravasation may result in severe local tissue necrosis; reduce dose in patients with impaired hepatic function
Vincristine (Vincasar PFS, Oncovin)
Mechanism of action is uncertain. May involve decrease in reticuloendothelial cell function or increase in platelet production.
Adult
Pediatric
0.6 mg/m2 IV on day 3 of each cycle
Acute pulmonary reaction may occur when taken concurrently with mitomycin-C; vaccination with live vaccines (eg, MMR) in immunosuppressed patients may result in severe or fatal infections
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in patients diagnosed with severe cardiopulmonary or hepatic impairment and patients with preexisting neuromuscular disease
Epirubicin (Ellence)
Cell cycle phase–nonspecific anthracycline derivative of doxorubicin with maximum cytotoxic effects on the S and G2 phases.
Adult
Pediatric
100 mg/m2 IV on day 1 q3wk for 3-6 cycles
Cimetidine decreases elimination; coadministration with other cardiotoxic drugs (eg, trastuzumab) may increase risk
Documented hypersensitivity; severe neutropenia; severe myocardial insufficiency or recent MI; previous treatment with anthracyclines to maximum cumulative dose; severe hepatic disease
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause myelosuppression; monitor for cardiac toxicity (not to exceed cumulative dose of 900 mg/m2); secondary leukemia has been reported; caution with renal or hepatic insufficiency (adjust dose); monitor for hyperuricemia secondary to tumor lysis syndrome
Cyclophosphamide (Neosar, Cytoxan)
Chemically related to nitrogen mustards. As an alkylating agent, mechanism of action of active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.
Adult
Pediatric
500 mg/m2 IV q3wk for 2-4 cycles
Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase half-life while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity; vaccination with live vaccines (eg, MMR) in immunosuppressed patients may result in severe or fatal infections
Documented hypersensitivity; severely depressed bone marrow function
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis; mesna may be administered in treatment regimen to decrease risk of hemorrhagic cystitis
Etoposide (Toposar, VePesid)
Inhibits topoisomerase II and causes DNA strand breakage, causing cell proliferation to arrest in late S or early G2 portion of cell cycle.
Adult
Pediatric
120 mg/m2 IV on days 1, 3, and 5 q3wk for 3-6 cycles
P-glycoprotein modulators (eg, cyclosporine, verapamil) can increase active etoposide metabolite concentrations and increase toxicity; may prolong effects of warfarin and increase clearance of methotrexate; cyclosporine and etoposide have additive effects in cytotoxicity of tumor cells
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Severe allergic reactions with anaphylaxis may occur; may cause myelosuppression, hepatotoxicity, or secondary AML
Somatostatin analogues
These agents are used in patients with somatostatin receptors. Octreotide, like natural somatostatin, inhibits secretion of growth hormone, insulin, and glucagon. Following IV administration of somatostatin analogues, basal serum growth hormone, insulin, and glucagon levels are lowered. They also inhibit prolactin secretion via vasoactive intestinal peptide-mediated and thyrotropin-releasing hormone-mediated secretion of prolactin. They are used in the treatment of acromegaly and hormone-secreting tumors.
Octreotide (Sandostatin)
Acts primarily on somatostatin receptor subtypes II and V. Inhibits GH secretion and has multitude of other endocrine and nonendocrine effects, including inhibition of glucagon, VIP, and GI peptides.
Adult
Pediatric
1.5 mg/d SC
May reduce effects of cyclosporine; patients receiving insulin, PO hypoglycemics, beta-blockers, and calcium channel blockers may require dosage adjustments
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adverse effects primarily are related to altered GI motility and include nausea, abdominal pain, diarrhea, and increased incidence of gallstones and biliary sludge; because of alteration in counter-regulatory hormones (insulin, glucagon, GH), hypoglycemia or hyperglycemia may be observed; bradycardia, cardiac conduction abnormalities, and arrhythmias have been reported; hypothyroidism may also occur because of inhibition of TSH secretion; exercise caution in patients with renal impairment; cholelithiasis may occur
Lanreotide (Somatuline Depot)
Indicated for long-term treatment of acromegaly in patients who experience inadequate response to other therapies. Octapeptide analogue of natural somatostatin. Inhibits a variety of endocrine, neuroendocrine, exocrine, and paracrine functions. Elicits high affinity for human somatostatin receptors 2, 3, and 5. Inhibits basal secretion of motilin, gastric inhibitory peptide, and pancreatic polypeptide. Markedly inhibits meal-induced increases in superior mesenteric artery blood flow and portal venous blood flow. Also significantly decreases prostaglandin E1—stimulated jejunal secretion of water, sodium, potassium, and chloride. Reduces prolactin levels in acromegalic patients when treated long term.
Adult
30 mg/d SC q14d
Note: Administer by deep SC injection in superior external quadrant of buttock; alternate injection sites
Pediatric
Not established
GI effects may decrease intestinal absorption of coadministered drugs; may decrease cyclosporine bioavailability; may cause additive effects to other drugs that decrease heart rate (eg, beta-blockers) or drugs that increase or decrease blood glucose levels
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Common adverse effects include diarrhea, abdominal pain, and nausea; less common adverse effects include constipation, gallstones, dermatitis, hyperglycemia, and hypoglycemia; rare instances of acute pancreatitis and slight decreases in thyroid function have been reported; cardiovascular effects (ie, bradycardia, myocardial infarction, hypertension, ventricular tachycardia) have also been reported; may initially cause redness, itching, and induration at injection site
Corticosteroids
These agents elicit anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.
Prednisone (Deltasone)
May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.
Adult
Pediatric
0.6 mg/kg/d PO for 3 mo, then decrease to 0.2 mg/kg/d
Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI ulceration
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, MG, growth suppression, and infections may occur with glucocorticoid use
Uroprotective antidote
Mesna is a prophylactic detoxifying agent used to inhibit hemorrhagic cystitis caused by ifosfamide and cyclophosphamide. In the kidney, mesna disulfide is reduced to free mesna. Free mesna has thiol groups that react with acrolein, the ifosfamide and cyclophosphamide metabolite considered responsible for urotoxicity.
Mesna (Mesnex)
Inactivates acrolein and prevents urothelial toxicity without affecting cytostatic activity.
Adult
Pediatric
Dose dependent on dose of ifosfamide or cyclophosphamide and is typically 60-100% of the antineoplastic agent used; may be administered as an initial bolus followed by either continuous IV infusion or intermittent IV infusions prior to and following chemotherapy regimen
May increase warfarin affect; adjust dose according to INR target
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Monitor morning urine for hematuria prior to ifosfamide or cyclophosphamide dose; common adverse effects include hypotension, headache, GI toxicity, and limb pain
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| Differential Diagnoses & Workup: Thymoma |
Treatment & Medication: Thymoma |
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References
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Further Reading
Keywords
thymoma, lymphoepithelioma, neoplasm of thymic epithelial cells, myasthenia gravis, MG, Lambert-Eaton myasthenic syndrome, LEMS, subacute sensory neuronopathy, red cell aplasia, immunodeficiency, Good syndrome, thymic epithelial tumor, TET, neuromyotonia, limbic encephalitis, polymyositis, subacute hearing loss, psychosis, sleep disorders, common variable immunodeficiency, CVID, superior vena cava syndrome, SVCS, mucocutaneous candidiasis, recurrent herpes simplex virus, varicella-zoster virus, cytomegalovirus, Pneumocystis carinii pneumonia, compression syndrome
Treatment & Medication: Thymoma