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Carboplatin–paclitaxel combination shows promise for rare form of thymus cancer
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The combination of carboplatin and paclitaxel compared favorably with standard anthracycline-based chemotherapy in the treatment of thymic carcinoma, according to results of a multicenter phase 2 study.
Patients with thymic carcinoma, a rare type of thymus gland cancer, have a very poor prognosis. Previous studies have included small numbers of patients, and the potential role of non–anthracycline-based chemotherapy — a standard treatment for non–small cell lung cancer — for treatment of thymic carcinoma is unclear, according to background information in the study.
Takashi Seto, MD, of the department of thoracic oncology at National Kyushu cancer Center in Japan, and colleagues conducted a single-arm study from May 2008 through November 2010 to assess carboplatin and paclitaxel in chemotherapy-naive patients with advanced thymic carcinoma.
The analysis included 39 patients. All patients received carboplatin (area under the curve, 6) and paclitaxel 200 mg/m² every 3 weeks for up to six cycles.
Objective response rate by independent review served as the primary endpoint. OS, PFS and safety served as secondary endpoints.
Researchers reported an overall response rate of 36% (95% CI, 21-53). One patient demonstrated a complete response and 13 demonstrated a partial response. Median PFS was 7.5 months (range, 6.2-12.3). Median OS was not reached.
Thirty-four patients (87%) developed grade 3 or grade 4 neutropenia. However, researchers reported no treatment-related deaths.
The findings suggest carboplatin plus paclitaxel may be an effective chemotherapy regimen for patients with thymic carcinoma, researchers concluded.
Disclosure: See the full study for a list of the researchers’ relevant financial disclosures.
Perspective
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Patrick J. Loehrer Sr., MD
Thymic malignancies are a very rare family of tumors that includes thymoma, thymic carcinoma and neuroendocrine carcinoma. Despite earlier speculations, thymic carcinoma is not a variant of thymoma, which has a greater sensitivity to anthracycline regimens, different surface markers and a greater propensity for paraneoplastic syndromes.The rarity of these tumors limits the conduct of prospective clinical trials, making this trial by Hirai and colleagues of interest. In a group of 39 evaluable patients, carboplatin plus paclitaxel produced a 36% response rate. The results of this study contrast with those of the Eastern Cooperative Oncology Group trial reported by Lemma and colleagues, which demonstrated only a 21.7% response rate in 23 patients with thymic carcinoma treated with the same drugs (Lemma GL. J Clin Oncol. 2011;29:2060-2065).
In both studies, central pathology review was conducted. Of note in the Hirai trial, 11 (28%) patients were reclassified as having poorly differentiated neuroendocrine carcinoma, 14 (36%) had tumors not otherwise specified, and one had non-small cell carcinoma of the lung. This is significant, as WHO histological classification now classifies neuroendocrine carcinomas separately from thymic carcinoma because of their unique clinicopathologic features.
The authors in the current study did not separate responses between patients with neuroendocrine carcinoma and those with classic thymic carcinoma. Regardless, several retrospective studies — and now two prospective studies — suggest modest activity for taxane-based chemotherapy in thymic carcinoma, providing a rationale for treatment of patients with advanced disease. My expectation is that the understanding of the unique driver pathways in the spectrum of thymic malignancies ultimately will lead to better targeted therapies and more impactful results.
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