Pediatric Thymoma Medication

  • Author: Richard A Bickel, MD; Chief Editor: Harumi Jyonouchi, MD  more...
 
Updated: Mar 21, 2016
 

Medication Summary

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.[35] 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.[36]

Various treatment protocols have been used, but those based on a combination of cisplatin and doxorubicin appear to have the best overall success rates. Additionally, National Comprehensive Cancer Network (NCCN) Guidelines currently recommend cisplatin/doxorubicin/cyclophosphamide as the primary treatment regimen.[31]

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.[37]

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.[38]

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%.[39]

Venuta's group prospectively studied 65 patients who were undergoing surgical resection of stage I, II, and III thymomas.[40] 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.

A Japan Clinical Oncology Group studied 23 patients who received cisplatin/vincristine/doxorubicin/etoposide before resection and/or radiotherapy. The overall survival rate at 5 years was 85%.[41]

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.[42]

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.[42]

Treatment protocols

Table. Macchiarini et al (1991)[38] (Open Table in a new window)

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



 

Table. Loehrer et al (1997)[39] (Open Table in a new window)

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

Table. Venuta et al (1997)[40] (Open Table in a new window)

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

Table. Palmieri et al (1999)[42] (Open Table in a new window)

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



 
Next

Antineoplastic agents

Class Summary

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.

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.

Vincristine (Vincasar PFS, Oncovin)

 

Mechanism of action is uncertain. May involve decrease in reticuloendothelial cell function or increase in platelet production.

Epirubicin (Ellence)

 

Cell cycle phase–nonspecific anthracycline derivative of doxorubicin with maximum cytotoxic effects on the S and G2 phases.

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.

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.

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Somatostatin analogues

Class Summary

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.

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.

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Corticosteroids

Class Summary

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.

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Uroprotective antidote

Class Summary

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.

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Contributor Information and Disclosures
Author

Richard A Bickel, MD Chief, Allergy Clinic, Moncrief Army Community Hospital

Richard A Bickel, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American College of Allergy, Asthma and Immunology

Disclosure: Nothing to disclose.

Coauthor(s)

Cecilia P Mikita, MD, MPH Associate Program Director, Allergy-Immunology Fellowship, Associate Professor of Pediatrics and Medicine, Uniformed Services University of the Health Sciences; Staff Allergist/Immunologist, Walter Reed National Military Medical Center

Cecilia P Mikita, MD, MPH is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David J Valacer, MD 

David J Valacer, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association for the Advancement of Science, American Thoracic Society, New York Academy of Sciences

Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD Faculty, Division of Allergy/Immunology and Infectious Diseases, Department of Pediatrics, Saint Peter's University Hospital

Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Pediatric Research, Society for Mucosal Immunology

Disclosure: Nothing to disclose.

Additional Contributors

Terry W Chin, MD, PhD Associate Clinical Professor, Department of Pediatrics, University of California, Irvine, School of Medicine; Associate Director, Cystic Fibrosis Center, Attending Staff Physician, Department of Pediatric Pulmonology, Allergy, and Immunology, Memorial Miller Children's Hospital

Terry W Chin, MD, PhD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American College of Chest Physicians, American Federation for Clinical Research, American Thoracic Society, California Society of Allergy, Asthma and Immunology, California Thoracic Society, Clinical Immunology Society, Los Angeles Pediatric Society, Western Society for Pediatric Research

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Marion Johnson, MD, to the development and writing of this article.

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Table 1. Comparison of the Different Classifications of Thymic Epithelial Tumors [27]
Clinicopathologic Classification WHO Type Terminology of the Histogenetic Classification for the Histologic Subtypes of Thymic Epithelial Tumors
Benign thymoma A



AB



Medullary thymoma



Mixed thymoma



Malignant thymomas,



Category I



B1



B2



B3



Predominantly cortical thymoma



Cortical thymoma



Well-differentiated thymic carcinoma



Malignant thymomas,



Category II



C Epidermoid keratinizing (squamous cell) carcinoma



Epidermoid nonkeratinizing carcinoma



Lymphoepithelioma-like carcinoma



Sarcomatoid carcinoma (carcinosarcoma)



Clear cell carcinoma



Mucoepidermoid carcinoma



Undifferentiated carcinoma



Table. Macchiarini et al (1991) [38]
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



 
Table. Loehrer et al (1997) [39]
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
Table. Venuta et al (1997) [40]
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
Table. Palmieri et al (1999) [42]
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



 
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