Our retrospective study analyzed the efficacy and safety of combined carboplatin plus nab-paclitaxel therapy in 12 previously untreated patients with advanced thymic carcinoma. While previous case reports have indicated the efficacy of this combination regimen for patients with this disease [15-17], no cohort studies have been performed to validate these claims. To the best of our knowledge, ours is the first study to evaluate the efﬁcacy of combination carboplatin plus nab-paclitaxel in patients with advanced thymic carcinoma.
Owing to its rarity, there is limited information regarding the efficacy of chemotherapy in patients with advanced thymic carcinoma. The cisplatin-doxorubicin-cyclophosphamide-vincristine (ADOC) regimen, which is an anthracycline-based multidrug treatment, is widely used as a ﬁrst-line chemotherapy in clinical practice [10, 18-20]. However, the adverse effects of anthracycline-based regimens, particularly hematological toxicities, are reportedly more severe than those of platinum-doublet regimens [18, 21-23]. Recently, the Japanese NEJ023 multi-institutional retrospective study revealed that carboplatin plus sb-paclitaxel produces similar outcomes as ADOC in patients with advanced thymic carcinoma . While there have been no prospective trials comparing ADOC to carboplatin/sb-paclitaxel, the NCCN guidelines currently recommend carboplatin/sb-paclitaxel as a ﬁrst-line chemotherapy for patients with advanced thymic carcinoma . Carboplatin plus nab-paclitaxel is a frequently used regimen for the treatment of advanced NSCLC in clinical practice; as such its application for the treatment for thymic carcinoma would be relatively straightforward. Additionally, administering this combined regimen would certainly be more convenient than delivering ADOC, as it is available on an outpatient basis.
A global phase III study revealed that nab-paclitaxel plus carboplatin yielded a significantly higher overall response rate than carboplatin plus sb-paclitaxel in patients with NSCLC . The authors of the study noted that patients with squamous cell histology responded remarkably well to nab-paclitaxel, suggesting that this agent is ideal for treating patients with that histological subtype . The most common histologic type of thymic carcinoma in Japan is squamous cell carcinoma; as such, Japanese patient populations ought to respond well to nab-paclitaxel . Based on the results of our study, carboplatin plus nab-paclitaxel therapy produced a high response rate, with PFS and OS comparable to those of patients with thymic carcinoma who received carboplatin plus sb-paclitaxel (Table 3).
It was previously found that carboplatin plus nab-paclitaxel therapy resulted in a significantly lower incidence rate of peripheral neuropathy among patients with NSCLC than did carboplatin plus sb-paclitaxel therapy ; this was further supported when using the FACT-Taxane tool, which showed a significant reduction in the development of neuropathy symptoms including neuropathic pain in the hands and feet . Moreover, we found that the proportion of patients experiencing peripheral neuropathy owing to carboplatin plus nab-paclitaxel therapy appeared to be lower than that reported in patients receiving carboplatin plus sb-paclitaxel (Table 3). Hence, carboplatin plus nab-paclitaxel therapy appears to be at least as beneficial in patients with thymic carcinoma as in those with NSCLC not only in terms of good efficacy but also the low frequency of sensory neuropathy.
A previous multi-institutional retrospective study that evaluated the efficacy of second-line chemotherapy for patients with advanced thymic carcinoma in which 57.6% of the subjects received second-line platinum-based doublets, 13.6% received other multidrug regimens (e.g., ADOC), and 28.8% received monotherapy found that the median OS from the start of second-line chemotherapy was 22.4 months while the response rate was 20.0% . Another multicenter, phase 2 trial of the vascular endothelial growth factor receptor kinase inhibitor lenvatinib [27, 28] found that this agent is effective and safe in patients with advanced thymic carcinoma in a second-line setting . Such findings suggest that second-line chemotherapy is valuable for patients with advanced thymic carcinoma. Of the 10 patients in our study who experienced disease progression while on carboplatin plus nab-paclitaxel, 8 (80%) received second-line chemotherapy given that their performance status did not deteriorate during first-line therapy. The preservation of performance status during first-line therapy is generally required for patients to be eligible for second-line therapy, which in turn may prolong survival time; our data indicate that carboplatin plus nab-paclitaxel is a reasonable option in this regard.
A limitation of our study is its retrospective design and small sample size; as such, our results cannot be considered definitive without additional validation.
In conclusion, carboplatin plus nab-paclitaxel showed favorable efficacy and safety as a first-line chemotherapy for patients with advanced thymic carcinoma. Given that this disease is rare, a multi-institutional non-randomized phase II study of the efficacy of this combination regimen is warranted.