A phase II trial of dose-dense chemotherapy, followed by surgical resection and/or thoracic radiotherapy, in locally advanced thymoma: report of a Japan Clinical Oncology Group trial (JCOG 9606)

Abstract

Background: This study aimed to evaluate the safety and efficacy of dose-dense weekly chemotherapy, followed by resection and/or thoracic radiotherapy.

Methods: Patients with histologically documented thymoma with unresectable stage III disease received 9 weeks of chemotherapy: cisplatin 25 mg m(-2) on weeks 1-9; vincristine 1 mg m(-2) on weeks 1, 2, 4, 6 and 8; and doxorubicin 40 mg m(-2) and etoposide 80 mg m(-2) on days 1-3 of weeks 1, 3, 5, 7 and 9. Patients went on to surgery and post-operative radiotherapy of 48 Gy; those with unresectable disease received 60 Gy radiotherapy.

Results: total of 23 patients were entered. The main toxicities of the chemotherapy regimen were neutropenia and anaemia, and 57% of patients completed the planned 9 weeks of therapy. There were no toxic deaths. Of the 21 eligible patients, 13 (62%) achieved a partial response (95% confidence interval: 38-82%). Thirteen patients underwent a thoracotomy and nine (39%) underwent complete resection. Progression-free survival at 2 and 5 years was 80 and 43%, respectively. Overall survival at 5 and 8 years was 85 and 69%, respectively. Survival did not seem to be affected by resection.

Conclusion: In thymoma patients, weekly dose-dense chemotherapy has activity similar to that of conventional regimens. Although some patients could achieve complete resection, the role of surgery remains unclear.

Figure 1

Study schema of the Japan Clinical Oncology Group (JCOG) 9606 trial, with the number of patients who actually received each of the protocol therapies. Cx, chemotherapy; RT, radiotherapy.

Figure 2

Progression-free survival (PFS) and overall survival (OS) of the 21 eligible patients.

Figure 3

Progression-free survival of the 21 eligible patients, according to the surgery undergone. Resection was performed in 11 patients (complete resection in nine), and 10 patients did not undergo resection (including two with probe thoracotomy). There was no significant difference (log rank P=0.75).

Figure 4

Overall survival of the 21 eligible patients, according to the surgery undergone. Resection was performed in 11 patients (complete resection in nine), and 10 patients did not undergo resection (including two with probe thoracotomy). There was no significant difference (log rank P=0.59).