As appropriate chemotherapeutic regimens in the first-line setting, platinum-based chemotherapy has shown some active efficacy and tolerability in patients with thymic epithelial tumors, including thymoma and TC. A recent review described that combinations of cisplatin-anthracycline or cisplatin-etoposide are recommended as first-line chemotherapy in such patients
[2][1].
Table 1 shows a summary of platinum-based chemotherapy as first-line treatment in patients with advanced TC. Previous studies have identified that cisplatin-adriamycin-cyclophosphamide (CAP), cisplatin-doxorubicin-cyclophoshamide-vincristine (ADOC), cisplatin-etoposide (VP16), cisplatin-docetaxel, and carboplatin-paclitaxel are the most common regimens administered in patients with TC
[2,4,5,6,7,8,9,10,11,12,13,14,15][1][2][3][4][5][6][7][8][9][10][11][12][13]. The overall response rate (ORR) of platinum-based chemotherapy was yielded approximately 30–40% (from 21% to 70%), regardless of the small sample size. Although high-intensity regimens, such as CAP or ADOC, increase the response rate, severe adverse events were also observed, although CAP is a standard regimen at least in Europe for thymoma
[4,5,6,7,8,9,10][2][3][4][5][6][7][8]. Meanwhile, cisplatin plus etoposide or carboplatin plus paclitaxel are commonly administered to patients with advanced non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC), known as active and tolerable regimens. Unfortunately, multidrug chemotherapy such as ADOC or CAP has been clarified as a toxic regimen, regardless of its high efficacy. Nowadays, the useful frequency of these heavy regimens gradually decreases due to the lack of significant improvement in the outcome compared to cisplatin plus etoposide or carboplatin plus paclitaxel. Considering the results of previous studies (
Table 1), the number of patients with TC registered in individual studies showed small sample sizes; therefore, it remains unclear which regimen is better as a standard treatment. However, the histological type of patients with TC predominantly consists of squamous cell carcinoma, similar to that of NSCLC. Recently, Ko et al. retrospectively analyzed the prognostic factors and efficacy of first-line chemotherapy in 286 patients with advanced TC in a multi-institutional study
[16][14]. In their study, the administration frequency of platinum-based doubles, monotherapy, and other multidrug chemotherapy such as ADOC was 62.2%, 3.5%, and 34.3%, respectively, and there was no significant difference in overall survival (OS) between different first-line therapeutic regimens (between carboplatin plus paclitaxel and ADOC, median OS: 27.8 vs. 29.9 months)
[16][14]. Of the 286 patients, carboplatin plus paclitaxel was administered to 70 patients with an ORR of 49%, cisplatin plus etoposide in 35 patients (ORR, 48.6%), cisplatin plus irinotecan in 16 patients (ORR, 66.7%), carboplatin plus etoposide in 15 patients (ORR, 30.8%), and cisplatin plus docetaxel in nine patients (ORR, 22.2%). As with other multidrug chemotherapy, the 79 patients who received ADOC achieved ORR of 41% and CAP were administered to eight patients with an ORR of 37.5%. They concluded that the efficacy of individual first-line regimens against advanced TC was not significantly different, and the use of carboplatin plus paclitaxel might be adequate as first-line chemotherapy
[16][14]. In terms of efficacy, tolerability, and histological similarity, carboplatin plus paclitaxel seems appropriate as first-line chemotherapy for patients with TC.
Table 1. Reports of platinum-based regimens as first line setting in thymic carcinoma.
First Author (Year) |
Ref. |
Regimens |
Thymoma + TC |
TC |
N |
ORR (%) |
N |
ORR (%) |
Platinum-anthracycline based chemotherapy |
Kim (2004) |
[6] | [4] |
CAP |
22 |
77% |
12 |
NA |
Li (2007) |
[4] | [2] |
CAP |
28 |
71% |
18 |
61% |
Cardillo (2010) |
[5] | [3] |
CAP |
21 |
58% |
10 |
50% |
Agatsuma (2011) |
[7] | [5] |
ADOC |
NA |
NA |
34 |
50% |
Rea (2011) |
[8] | [6] |
ADOC |
38 |
68% |
6 |
50% |
Yoh (2003) |
[17] | [15] |
CODE |
NA |
NA |
12 |
42% |
Oshita (1995) |
[9] | [7] |
CAP-VP16 |
14 |
43% |
7 |
42% |
Thomas (2014) |
[10] | [8] |
CAP-belionstat |
26 |
40% |
14 |
21% |
Platinum-etoposide based chemotherapy |
Loehrer (2001) |
[11] | [9] |
CDDP+VP16-IFO |
28 |
32% |
8 |
NA |
Grassin (2010) |
[12] | [10] |
CDDP+VP16-IFO |
16 |
25% |
4 |
25% |
Platinum-taxane based chemotherapy |
Park (2013) |
[13] | [11] |
CDDP-DTX |
27 |
63% |
18 |
66% |
Kim (2015) |
[14] | [12] |
CDDP-PTX |
42 |
63% |
28 |
70% |
Lemma (2011) |
[2] | [1] |
CBDCA-PTX |
44 |
32% |
23 |
21.7% |
Igawa (2010) |
[15] | [13] |
CBDCA-PTX |
NA |
NA |
11 |
36% |
Furugen (2011) |
[18] | [16] |
CBDCA-PTX |
NA |
NA |
16 |
37.5% |
Hirai (2015) |
[19] | [17] |
CBDCA-PTX |
NA |
NA |
39 |
35.9% |
Platinum-doublet other chemotherapy |
Okuma (2011) |
[20] | [18] |
CDDP-irinotecan |
NA |
NA |
9 |
55.6% |
Luo (2016) |
[21] | [19] |
CDDP-gemcitabine |
NA |
NA |
13 |
61.5% |