High-dose carboplatin with etoposide in patients with recurrent thymoma: the Indiana University experience

Abstract

Summary:Thymoma is a chemotherapy-sensitive tumor with a 30-50% 5-year survival in previously untreated patients. Unfortunately, durable CRs with salvage chemotherapy are rarely observed. We initiated a phase II trial of high-dose carboplatin and etoposide in patients with relapsed thymoma or thymic carcinoma. All patients had progressive disease (PD) after initial or salvage chemotherapy, but were not cisplatin-refractory. PBSCs were mobilized using 10 g/kg/day G-CSF. Patients received carboplatin 700 mg/m 2 and etoposide 750 mg/m 2 i.v. on days −5, −4, −3. Five patients were enrolled and evaluated after tandem transplants 4 weeks apart. All patients had pleural-based and lung parenchymal metastasis, one or two prior surgeries and two or more courses of prior cisplatin-based chemotherapy regimens. Chemotherapy was well tolerated, although grade IV hematological toxicity occurred in all patients. Progression-free survival following HDC ranged from 3.5 to 16.5 months. One patient maintained a CR for 12.8 months, then died from an unrelated cause. With a minimum of 2 years follow-up for all patients, three of five patients remain alive at 26+, 36+, and 49+ months. High-dose carboplatin and etoposide in relapsed thymoma is feasible with acceptable toxicity; however, these limited data do not appear superior to standard-dose salvage therapy. Bone Marrow Transplantation (2001) 28, 435-438. Keywords: autologous stem cell transplantation; thymoma; relapsed disease Thymomas are infrequent tumors, but are the most common neoplasm of the anterior mediastinum. 1 They are chemosensitive with objective responses observed with single agent and combination chemotherapy. For patients with unresectable locally advanced disease, cisplatin, doxorubicin plus cyclophosphamide (PAC) produced an overall response rate of 70% prior to radiation therapy and 5-year overall survival of 52.5% in a small prospective intergroup trial. 2 However, durable CRs are rarely observed with standard salvage chemotherapy for relapsed disease.Indiana University has experience with high-dose carboplatin and etoposide in the treatment of high risk and relapsed germ cell tumors. Patients with testicular cancer who are not cured with cisplatin-combination chemotherapy and aggressive surgical extirpation can achieve long-term remissions and cures with high-dose carboplatin and etoposide followed by peripheral blood stem cell (PBSC) transplantation. 3 Based on the germ cell model, we initiated this phase II study to investigate the efficacy of high-dose carboplatin and etoposide with PBSCT in patients with recurrent thymoma or thymic carcinoma. This approach was supported by a trial conducted by the EORTC which reported a 50% response rate in patients treated with conventional dosage cisplatin plus etoposide in advanced thymoma. 4

A phase-II trial of dose-dense chemotherapy in patients with disseminated thymoma: report of a Japan Clinical Oncology Group trial (JCOG 9605)

“…However, another intensive chemotherapy, ETP -IFX -CDDP (VIP) supported by G-CSF, has also reported disappointingly low response rates and no better survival . Hanna et al (2001) reported five patients with prior chemotherapy treated with highdose chemotherapy and stem cell support, but concluded that no superiority to conventional therapy was evident. Taken together with our results, intensification of chemotherapy does not appear sufficiently promising for treating advanced thymoma.…”

Haemorrhagic brain metastasis from a thymic carcinoma

“…2;3;24 . Hanna et al 5 report that thymic carcinoma are chemotherapy-sensitive tumours with a 30-50 % 5-year survival.…”

“…5 Neuroendocrine tumours, also found in the thymus, arise from Kulchitsky cells and vary in malignant potential. The histopathological classification and anatomical staging of primary thymic tumours remain controversial.…”

Chemotherapy in the treatment of thymic tumors

“…While the strategy of high-dose chemotherapy with stem cell support was feasible and demonstrated acceptable toxicity, the number of patients treated in the Indiana University series was small (4 patients with recurrent thymoma and 1 with recurrent thymic carcinoma) and the outcomes were no better than those obtained with standard chemotherapy regimens [32].…”