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 |
|
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.
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.
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.
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.
Tables
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 |
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 |
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 |
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 |
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 |
|
