Difference between revisions of "Thymoma"
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!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
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− | |[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142%2820010601%2991:11<2010::AID-CNCR1226>3.0.CO;2-2 | + | |[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142%2820010601%2991:11<2010::AID-CNCR1226>3.0.CO;2-2 Loehrer et al. 2001] |
|style="background-color:#91cf61"|Phase 2 | |style="background-color:#91cf61"|Phase 2 | ||
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===References=== | ===References=== | ||
− | # Loehrer PJ Sr, Jiroutek M, Aisner S, Aisner J, Green M, Thomas CR Jr, Livingston R, Johnson DH. Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma: an intergroup trial. Cancer. 2001 Jun 1;91(11):2010-5. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142%2820010601%2991:11<2010::AID-CNCR1226>3.0.CO;2-2 | + | # Loehrer PJ Sr, Jiroutek M, Aisner S, Aisner J, Green M, Thomas CR Jr, Livingston R, Johnson DH. Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma: an intergroup trial. Cancer. 2001 Jun 1;91(11):2010-5. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142%2820010601%2991:11<2010::AID-CNCR1226>3.0.CO;2-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11391579 PubMed] |
=Advanced or metastatic disease, subsequent lines of therapy= | =Advanced or metastatic disease, subsequent lines of therapy= |
Revision as of 22:41, 16 September 2022
14 regimens on this page
16 variants on this page
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Guidelines
ESMO
- 2015: Girard et al. Thymic epithelial tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
NCCN
Neoadjuvant therapy for borderline resectable disease
PAC
PAC: Platinol (Cisplatin), Adriamycin (Doxorubicin), Cyclophosphamide
CAP: Cyclophosphamide, Adriamycin (Doxorubicin), Platinol (Cisplatin)
Regimen
Study | Evidence |
---|---|
Kim et al. 2004 | Phase 2 |
Note: while this regimen is conventionally referred to as PAC or CAP, it also includes a high-dose prednisone component with likely antineoplastic properties.
Chemotherapy
- Cisplatin (Platinol) 30 mg/m2 IV once per day on days 1 to 3
- Doxorubicin (Adriamycin) 20 mg/m2/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 60 mg/m2)
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV slow push once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive medications
- Metoclopramide (Reglan) 1 mg/kg IV once per day on days 1 to 3, prior to chemotherapy
- Diphenhydramine (Benadryl) 25 mg IV once per day on days 1 to 3, prior to chemotherapy
21- to 28-day cycle for 3 cycles
Subsequent treatment
- Surgical resection is performed if CT scan 3 to 4 weeks after the third cycle of chemotherapy shows disease amenable to resection, and is followed by RT, then PAC consolidation
References
- Kim ES, Putnam JB, Komaki R, Walsh GL, Ro JY, Shin HJ, Truong M, Moon H, Swisher SG, Fossella FV, Khuri FR, Hong WK, Shin DM. Phase II study of a multidisciplinary approach with induction chemotherapy, followed by surgical resection, radiation therapy, and consolidation chemotherapy for unresectable malignant thymomas: final report. Lung Cancer. 2004 Jun;44(3):369-79. link to original article contains dosing details in manuscript PubMed
Adjuvant therapy
PAC
PAC: Platinol (Cisplatin), Adriamycin (Doxorubicin), Cyclophosphamide
CAP: Cyclophosphamide, Adriamycin (Doxorubicin), Platinol (Cisplatin)
Regimen
Study | Evidence |
---|---|
Kim et al. 2004 | Phase 2 |
Note: while this regimen is conventionally referred to as PAC or CAP, it also includes a high-dose prednisone component with likely antineoplastic properties. Also note that these doses are 80% of the induction doses, except for the prednisone.
Preceding treatment
Chemotherapy
- Cisplatin (Platinol) 24 mg/m2 IV once per day on days 1 to 3
- Doxorubicin (Adriamycin) 16 mg/m2/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 48 mg/m2)
- Cyclophosphamide (Cytoxan) 400 mg/m2 IV slow push once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21- to 28-day cycle for 3 cycles
References
- Kim ES, Putnam JB, Komaki R, Walsh GL, Ro JY, Shin HJ, Truong M, Moon H, Swisher SG, Fossella FV, Khuri FR, Hong WK, Shin DM. Phase II study of a multidisciplinary approach with induction chemotherapy, followed by surgical resection, radiation therapy, and consolidation chemotherapy for unresectable malignant thymomas: final report. Lung Cancer. 2004 Jun;44(3):369-79. link to original article contains dosing details in manuscript PubMed
Radiation therapy
Regimen
Study | Evidence |
---|---|
Kim et al. 2004 | Phase 2 |
Preceding treatment
- PAC induction, then surgery (in some cases)
Radiotherapy
- If tumor is completely resected and has at least 80% necrosis: 50 Gy External beam radiotherapy is administered 3 to 6 weeks after surgery
- If tumor is incompletely resected or has less than 80% necrosis: 60 Gy External beam radiotherapy is administered
One course
Subsequent treatment
- PAC x 3
References
- Kim ES, Putnam JB, Komaki R, Walsh GL, Ro JY, Shin HJ, Truong M, Moon H, Swisher SG, Fossella FV, Khuri FR, Hong WK, Shin DM. Phase II study of a multidisciplinary approach with induction chemotherapy, followed by surgical resection, radiation therapy, and consolidation chemotherapy for unresectable malignant thymomas: final report. Lung Cancer. 2004 Jun;44(3):369-79. link to original article contains dosing details in manuscript PubMed
Advanced or metastatic disease, first-line therapy
ADOC
ADOC: Adriamycin (Doxorubicin), cis-Diamminedichloroplatinum (Cisplatin), Oncovin (Vincristine), Cyclophosphamide
Regimen
Study | Evidence |
---|---|
<30::AID-CNCR2820680106>3.0.CO;2-4 Fornasiero et al. 1991 | Retrospective |
Note: The body of Fornasiero et al. 1991 specifies that cycles are given every 3 weeks. However, the abstract says that cycles are given "at monthly intervals," and some guidelines list the regimen as being given every 4 weeks.
Chemotherapy
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 0.6 mg/m2 IV once on day 3
- Cyclophosphamide (Cytoxan) 700 mg/m2 IV once on day 4
21- to 28-day cycles
References
- Retrospective: Fornasiero A, Daniele O, Ghiotto C, Piazza M, Fiore-Donati L, Calabró F, Rea F, Fiorentino MV. Chemotherapy for invasive thymoma. A 13-year experience. Cancer. 1991 Jul 1;68(1):30-3. <30::AID-CNCR2820680106>3.0.CO;2-4 link to original article contains dosing details in manuscript PubMed
Carboplatin & Paclitaxel (CP)
Regimen
Study | Evidence |
---|---|
Lemma et al. 2011 | Phase 2 |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV over 30 minutes once on day 1, given second
- Paclitaxel (Taxol) 225 mg/m2 IV over 3 hours once on day 1, given first
Supportive medications
- Cimetidine (Tagamet) 300 mg IV once on day 1; 60 minutes prior to Paclitaxel (Taxol)
- Diphenhydramine (Benadryl) 25 mg IV once on day 1; 60 minutes prior to Paclitaxel (Taxol)
- Dexamethasone (Decadron) 20 mg IV once on day 1; 60 minutes prior to Paclitaxel (Taxol)
21-day cycle for up to 6 cycles
References
- Lemma GL, Lee JW, Aisner SC, Langer CJ, Tester WJ, Johnson DH, Loehrer PJ Sr. Phase II study of carboplatin and paclitaxel in advanced thymoma and thymic carcinoma. J Clin Oncol. 2011 May 20;29(15):2060-5. Epub 2011 Apr 18. link to original article contains dosing details in manuscript link to PMC article PubMed
Cisplatin & Etoposide (EP)
PE: Platinol (Cisplatin), Etoposide
Regimen
Study | Evidence |
---|---|
Giaccone et al. 1996 | Phase 2 |
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV over 60 minutes once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV over at least 30 minutes once per day on days 1 to 3
Supportive medications
- "A program of forced hydration"
21-day cycle for up to 8 cycles
References
- Giaccone G, Ardizzoni A, Kirkpatrick A, Clerico M, Sahmoud T, van Zandwijk N; EORTC Lung Cancer Cooperative Group. Cisplatin and etoposide combination chemotherapy for locally advanced or metastatic thymoma: a phase II study of the European Organisation for Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol. 1996 Mar;14(3):814-20. link to original article contains dosing details in manuscript PubMed
PAC
PAC: Platinol (Cisplatin), Adriamycin (Doxorubicin), Cyclophosphamide
CAP: Cyclophosphamide, Adriamycin (Doxorubicin), Platinol (Cisplatin)
Regimen
Study | Evidence |
---|---|
Loehrer et al. 1990 | Phase 2 |
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV over at least 1 hour once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV slow push once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV slow push once on day 1
Supportive medications
- 1 liter NS over 2 hours at least 2 hours before and after Cisplatin (Platinol) therapy
- Corticosteroids use for antiemesis was specifically discouraged unless the indication was for myasthenia gravis
21-day cycle for up to 8 cycles
References
- Loehrer PJ Sr, Perez CA, Roth LM, Greco A, Livingston RB, Einhorn LH. Chemotherapy for advanced thymoma: preliminary results of an intergroup study. Ann Intern Med. 1990 Oct 1;113(7):520-4. link to original article contains dosing details in manuscript PubMed
- Update: Loehrer PJ Sr, Kim K, Aisner SC, Livingston R, Einhorn LH, Johnson D, Blum R; Eastern Cooperative Oncology Group; Southwest Oncology Group; Southeastern Cancer Study Group. Cisplatin plus doxorubicin plus cyclophosphamide in metastatic or recurrent thymoma: final results of an intergroup trial. J Clin Oncol. 1994 Jun;12(6):1164-8. link to original article contains dosing details in manuscript PubMed
VIP
VIP: Vepesid (Etoposide), Ifosfamide, Platinol (Cisplatin)
Regimen
Study | Evidence |
---|---|
<2010::AID-CNCR1226>3.0.CO;2-2 Loehrer et al. 2001 | Phase 2 |
Chemotherapy
- Etoposide (Vepesid) 75 mg/m2 IV once per day on days 1 to 4
- Ifosfamide (Ifex) 1200 mg/m2 IV once per day on days 1 to 4
- Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 to 4
Supportive medications
- Mesna (Mesnex) 240 mg/m2 IV push two times per day on days 1 to 4, given 4 hours after and 8 hours after Ifosfamide (Ifex) (total dose per cycle: 1920 mg/m2)
- 1 liter normal saline once per day on days 1 to 4, prior to Cisplatin (Platinol)
- Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 5 to 15, until WBC count at least 10 x 109/L above nadir
21-day cycle for 4 cycles
References
- Loehrer PJ Sr, Jiroutek M, Aisner S, Aisner J, Green M, Thomas CR Jr, Livingston R, Johnson DH. Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma: an intergroup trial. Cancer. 2001 Jun 1;91(11):2010-5. <2010::AID-CNCR1226>3.0.CO;2-2 link to original article contains dosing details in manuscript PubMed
Advanced or metastatic disease, subsequent lines of therapy
Capecitabine & Gemcitabine
CAP-GEM: CAPecitabine & GEMcitabine
Regimen
Study | Evidence | Efficacy |
---|---|---|
Palmieri et al. 2009 | Phase 2 | ORR: 40% |
Chemotherapy
- Capecitabine (Xeloda) 650 mg/m2 PO twice per day on days 1 to 14
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycles
References
- Palmieri G, Merola G, Federico P, Petillo L, Marino M, Lalle M, Milella M, Ceribelli A, Montella L, Merola C, Del Prete S, Bergaglio M, De Placido S, Di Lorenzo G. Preliminary results of phase II study of capecitabine and gemcitabine (CAP-GEM) in patients with metastatic pretreated thymic epithelial tumors (TETs). Ann Oncol. 2010 Jun;21(6):1168-72. Epub 2009 Oct 30. link to original article PubMed
- Update: Palmieri G, Buonerba C, Ottaviano M, Federico P, Calabrese F, Von Arx C, De Maio AP, Marino M, Lalle M, Montella L, Merola C, Milella M, Bergaglio M, Di Lorenzo G, Damiano V. Capecitabine plus gemcitabine in thymic epithelial tumors: final analysis of a Phase II trial. Future Oncol. 2014 Nov;10(14):2141-7. link to original article contains dosing details in abstract PubMed
Everolimus monotherapy
Regimen
Study | Evidence | Efficacy |
---|---|---|
Zucali et al. 2017 (ONC-2010-001) | Phase 2 | DCR: 88% |
Targeted therapy
- Everolimus (Afinitor) 10 mg PO once per day
Continued indefinitely
References
- ONC-2010-001: Zucali PA, De Pas T, Palmieri G, Favaretto A, Chella A, Tiseo M, Caruso M, Simonelli M, Perrino M, De Vincenzo F, Toffalorio F, Damiano V, Pasello G, Garbella E, Ali M, Conforti F, Ottaviano M, Cioffi A, De Placido S, Giordano L, Bertossi M, Destro A, Di Tommaso L, Santoro A. Phase II study of everolimus in patients with thymoma and thymic carcinoma previously treated with cisplatin-based chemotherapy. J Clin Oncol. 2018 Feb 1;36(4):342-349. Epub 2017 Dec 14.link to original article contains dosing details in manuscript PubMed
Ifosfamide monotherapy
Regimen variant #1, intermittent dosing
Study | Evidence |
---|---|
Highley et al. 1999 | Pilot, <20 pts |
Chemotherapy
- Ifosfamide (Ifex) 1500 mg/m2 IV over 30 minutes once per day on days 1 to 5
Supportive medications
- Mesna (Mesnex) 400 mg IV bolus once per day on days 1 to 5, given before ifosfamide, then 1000 mg/m2 IV over 7.5 hours (total dose per cycle: 7000 mg/m2)
21-day cycles
Regimen variant #2, continuous dosing
Study | Evidence |
---|---|
Highley et al. 1999 | Pilot, <20 pts |
Chemotherapy
- Ifosfamide (Ifex) 1500 mg/m2/day IV continuous infusion over 120 hours, started on day 1, given second (total dose per cycle: 6000 mg/m2)
Supportive medications
- Mesna (Mesnex) 2000 mg IV bolus once on day 1, given first, then 1500 mg/m2/day IV continuous infusion over 7 days (total dose per cycle: 12,500 mg/m2)
21-day cycles
References
- Highley MS, Underhill CR, Parnis FX, Karapetis C, Rankin E, Dussek J, Bryant B, Rowland C, Hodson N, Hughes J, Harper PG. Treatment of invasive thymoma with single-agent ifosfamide. J Clin Oncol. 1999 Sep;17(9):2737-44. link to original article contains dosing details in manuscript PubMed content property of HemOnc.org
Octreotide monotherapy
Regimen variant #1, brief course
Study | Evidence |
---|---|
Loehrer et al. 2004 | Phase 2 |
Endocrine therapy
- Octreotide (Sandostatin) 0.5 mg SC three times per day
1-month cycle for 2 cycles
Subsequent treatment
- If stable disease, patients would transition to octreotide & prednisone
Regimen variant #2, extended course
Study | Evidence |
---|---|
Loehrer et al. 2004 | Phase 2 |
Endocrine therapy
- Octreotide (Sandostatin) 0.5 mg SC three times per day
1-month cycle for up to 12 cycles
References
- Loehrer PJ Sr, Wang W, Johnson DH, Aisner SC, Ettinger DS; Eastern Cooperative Oncology Group. Octreotide alone or with prednisone in patients with advanced thymoma and thymic carcinoma: an Eastern Cooperative Oncology Group Phase II Trial. J Clin Oncol. 2004 Jan 15;22(2):293-9. link to original article contains dosing details in manuscript PubMed
Octreotide & Prednisone
Regimen
Study | Evidence |
---|---|
Loehrer et al. 2004 | Phase 2 |
Preceding treatment
- Octreotide x 2 mo
Endocrine therapy
- Octreotide (Sandostatin) 0.5 mg SC three times per day
- Prednisone (Sterapred) 0.6 mg/kg PO once per day
1-month cycle for up to 10 cycles
References
- Loehrer PJ Sr, Wang W, Johnson DH, Aisner SC, Ettinger DS; Eastern Cooperative Oncology Group. Octreotide alone or with prednisone in patients with advanced thymoma and thymic carcinoma: an Eastern Cooperative Oncology Group Phase II Trial. J Clin Oncol. 2004 Jan 15;22(2):293-9. link to original article contains dosing details in manuscript PubMed
Sunitinib monotherapy
Regimen
Study | Evidence |
---|---|
Thomas et al. 2015 (NCI 12-C-0118) | Phase 2 |
Targeted therapy
- Sunitinib (Sutent) 50 mg PO once per day on days 1 to 28
42-day cycles
References
- NCI 12-C-0118: Thomas A, Rajan A, Berman A, Tomita Y, Brzezniak C, Lee MJ, Lee S, Ling A, Spittler AJ, Carter CA, Guha U, Wang Y, Szabo E, Meltzer P, Steinberg SM, Trepel JB, Loehrer PJ, Giaccone G. Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: an open-label phase 2 trial. Lancet Oncol. 2015 Feb;16(2):177-86. Epub 2015 Jan 13. Erratum in: Lancet Oncol. 2015 Mar;16(3):e105. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01621568
Investigational agents
Drugs with preliminary evidence of efficacy in this disease subtype.