Pushing an Old Issue Towards a New Front Line

Abstract

Selection of an appropriate chemotherapeutic regimen for treating patients with advanced stage rare cancer is difficult. Thymic carcinoma is one such cancer for which the available information is insufficient and there is no established standard therapy. Furugen et al. (1) reported a retrospective clinical study in which 16 patients with advanced thymic carcinoma were treated with combination chemotherapy consisting of carboplatin and paclitaxel. Although the National Comprehensive Cancer Network (NCCN) provides guidelines (2) for chemotherapeutic regimens for this disease, there is no clear distinction between thymic carcinoma and thymoma, which are distinctive clinicopathologic entities. As summarized in Table 1, the guidelines are based on six small studies (3–8), mostly retrospective, consisting of 137 and 31 patients with thymoma and thymic carcinoma, respectively. Are you willing to treat your patients according to guidelines based on 31 patients? The last version of PDQ (9) distinguishes between these two diseases; however, the description regarding chemotherapy for thymic carcinoma is based on four references, including two case reports. In the light of this situation, the study of Furugen et al. using combination chemotherapy appears to be important. This regimen should be further investigated with prospective Phase II studies, and subsequent large-scale Phase III studies. If you follow the rule, then how many decades should patients wait? This issue reminded me of a new paradigm of personalized cancer therapy. We now know that common cancers can be further divided into different subtypes. More information on targeting molecules would exponentially further subdivide these subtypes in the very near future. Screening for EGFR mutations is now an old mission. We will soon be struggling to screen for the ALK fusion gene in 3–5% of patients with adenocarcinoma of the lung. Pancreatic cancer is a relatively rare disease compared with lung cancer. Anti-EGFR antibody therapy was reportedly ineffective in prolonging the survival of patients with pancreatic cancer (10), of which .70% harbor KRAS mutations. Well-designed clinical trials for colorectal carcinoma showed that anti-EGFR antibodies were ineffective for tumors possessing active KRAS mutations (11–13). How do anti-EGFR antibodies affect patients with pancreatic cancer and wild-type KRAS? The answer may involve screening for wild-type KRAS in ,30% of pancreatic cancer patients, which would be a timeconsuming task. With regard to the previously mentioned issue of thymic carcinoma, Furugen et al. discussed the role of KIT mutation in the disease and possible roles of imatinib and sorafenib. Tissue banks or biobanks might be required to fight against subdivided common and rare cancers. We may need to reorganize clinical study groups to stand up to the reorganized clinical entities in the front line. The traditional approach does not appear to be feasible for establishing standard therapy for patients with rare cancers. With the development of bioscience technologies, we can now attempt to use different approaches.