2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

Table 1. Selected Studies Reporting on Preoperative Chemotherapy or Chemoradiation for Locally Advanced Thymic Tumors
Study
Primary
Chemotherapy
Regimen
No. of
Patients
Tumor
Type Stage
surgical candidate—either because R0 resection was not
thought to be achievable or because of poor performance
status or coexistent medical condition—curative-intent, definitive
radiotherapy was delivered. Loehrer and colleagues
reported a phase II trial including 23 patients with thymoma
and treated with cyclophosphamide, doxorubicin, and
cisplatin (CAP) chemotherapy followed by radiotherapy to a
total dose of 54 Gy. 25 Five-year survival was 53%.
Of note, two studies including patients with locally advanced
thymic tumors reported on the use of primary
chemotherapy associated with sequential or concurrent ra-
Design
Response
Rate (%)
Any
Surgery
diotherapy in a preoperative intent (Table 1). Available
retrospective data do not provide interpretable results comparing
chemotherapy with chemoradiotherapy in the preoperative
setting. A randomized phase II trial is currently
ongoing, evaluating cisplatin and etoposide chemotherapy
combined with conformal or intensity-modulated radiotherapy
as primary treatment of locally advanced thymoma and
thymic carcinoma (clinicaltrials.gov ID: NCT00387868).
After primary chemotherapy, if radiotherapy was not
feasible because of a large tumor burden that precluded safe
delivery of appropriate doses or because of comorbidities
increasing the risks of radiation-induced toxicity, treatment
consisted of chemotherapy alone in a strategy that may
ultimately be considered palliative. In the reported literature,
approximately 15% to 20% of patients with locally
advanced thymic tumors receiving upfront chemotherapy
did not receive either surgery or radiation therapy or other
local treatment (Table 1). Survival of these patients was
limited.
Consolidation Chemotherapy
Surgery
Subsequent Treatment (%)
Complete
Resection
Radiotherapy None
Chemotherapy
Macchiarini et al 1991 14 CEE 7 T/TC III Phase II 100 100 57 0 0
Berruti et al 1993 15 ADOC 6 T III-IVA Phase II 83 NA 17 NA NA
Rea et al 1993 16 ADOC 16 T III-IVA Retrosp 100 100 69 0 0
Berruti et al 1999 17 ADOC 16 T III-IVA Phase II 81 56 56 31 13
Venuta et al 2003 18 CEE 15 T/TC III Retrosp 66 100 NA NA NS
Bretti et al 2004 19 ADOC/PE 25 T/TC III-IVA Retrosp 72 68 44 NA NA
Kim et al 2004 20 CAPP 22 T Phase II 77 100 72 0 0
Lucchi et al 2005 21 CEE 36 T/TC III-IVA Retrosp 67 69 78 19 3
Jacot et al 2005 22 CAP 5 T/TC III-IVA Retrosp 75 38 25 50 12
Yokoi et al 2007 23 CAMP 14 T/TC III, IV Retrosp 93 64 14 14 21
Kunitoh et al 2009 24 CODE 21 T III Phase II 62 62 43 24 14
Chemoradiation
Loehrer et al 199725 CAP/54 Gy 23 T/TC III-IVA Phase II 70 0 0 0 100
Wright et al 200826 PE, ADOC, CAP,
CEE/45–60 Gy
10 T/TC III-IVA Retrosp 40 100 80 0 0
Abbreviations: T, thymoma; TC, thymic carcinoma; Retrosp, retrospective; CAP, cisplatin (50 mg/m 2 /3 weeks), doxorubicin (50 mg/m 2 /3 weeks), cyclophosphamide
(500 mg/m 2 /3 weeks); ADOC, doxorubicin (40 mg/m 2 /3 weeks), cisplatin (50 mg/m 2 /3 weeks), vincristine (0.6 mg/m 2 /3 weeks), cyclophosphamide (700 mg/m 2 /3 weeks);
PE, cisplatin (60 mg/m 2 /3 weeks), etoposide (120 mg/m 2 � 3/3 weeks); CODE, cisplatin (25 mg/m 2 /week), vincristine (1 mg/m 2 /week), doxorubicin (40 mg/m 2 /week),
etoposide (80 mg/m 2 � 3 days/week); CEE, cisplatin (75 mg/m 2 /3 weeks), epirubicin (100 mg/m 2 /3 weeks), etoposide (120 mg/m 2 � 3 days/3weeks); CAMP, CAP plus
prednisolone (1000 mg/m 2 � 4 days, 500 mg/m 2 � 2 days/3 weeks); NA, not available.
KEY POINTS
● Surgery is the mainstay of the treatment of thymic
malignancies. Chemotherapy is recommended in unresectable,
locally advanced, and metastatic tumors.
● Thymomas are chemosensitive. Major regimens are
based on doxorubicin and cisplatin. No randomized
trial is available that compares different cytotoxic
agent combinations.
● Preoperative chemotherapy is recommended for unresectable,
locally advanced thymomas, aiming at
allowing subsequent R0 resection, which is the major
predictor of long-term survival.
● Adjuvant chemotherapy is not recommended for thymomas,
but may be used for thymic carcinomas.
● Targeted therapies have been developed empirically
in refractory thymomas, with limited rationale and
poor patient selection. The use of targeted agents in
thymic tumors is currently investigational, not a
routine practice, because other options may exist for
refractory tumors.
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NICOLAS GIRARD
Consolidation chemotherapy refers to chemotherapy delivered
after multimodal, curative-intent treatment, aiming
at treating possible residual microscopic disease after surgery.
This strategy has been reported by investigators
from the M. D. Anderson Cancer Center (Houston, TX). 20
Patients with stage III to IV thymoma received upfront
chemotherapy with three cycles of CAPP (CAP plus prednisone),
followed by surgery and adjuvant radiotherapy, followed
by consolidation chemotherapy with three cycles of
CAPP. Contrary to adjuvant chemoradiation, which usually
consists of chemotherapy followed by radiotherapy, consolidation
chemotherapy was delivered after adjuvant radiotherapy.
The role of consolidation chemotherapy within such
multimodal strategy has not been specifically evaluated.