Recently, it has become apparent that invasive thymoma is relatively sensitive to combination chemotherapy and that survival is relatively long. In two fairly large series using the РАСregimen or a combination of cisplatin, doxorubicin, vincristine, and cyclophosphamide, overall response rates ranged from 70 to 91.8%, with median durations of response averaging 11.9 months and median survival ranging from 15 to 37.7 months. Recendy, РАСwith etoposide and concurrent granulocyte colony-stimulating factor had been used for advanced thymoma or thymic cancer with a reported 42.9% response rate (all partial remissions) but with significant bone marrow toxicity. The РАСregimen was chosen for our patients because of the favorable response rates noted. We substituted carboplatin for cisplatin for easier outpatient administration. The concurrent use of oral prednisone in case 1 was not a likely confounding factor because his tumor progressed during low-dose steroid therapy.

Our patients developed progressive thymoma after ini­tially responding to combination chemotherapy consisting of cyclophosphamide, doxorubicin, and carboplatin. The standard treatment options for this situation, in order of decreasing effectiveness, are a subsequent surgical resection, radiotherapy, and corticosteroid use. There are reports of small prospective trials of second-line chemotherapy using various regimens (single or in combination) with disappoint­ing results.3 7 The role of low-dose oral etoposide in the management of recurrent thymoma has not been evaluated in clinical trials although there are reports of some efficacy as first-line therapy in combination with cisplatin. We elected to use the same chemotherapeutic regimen to treat our patients’ recurrences because their disease had re­sponded to the РАСregimen previously, because the disease-free interval was greater than 6 months, and because there was evidence that secondary responses occurred with the same regimen in lung, breast, and ovarian cancers as well as in Hodgkin’s lymphomas. Higher response rates were noted when the disease-free intervals were greater than 12 months in breast cancer, 24 months in epithelial ovarian cancer, and 12 months in Hodgkin’s lymphoma. The disease-free intervals in our patients were 14 and 60 months, respectively.  

Several investigators have reported cases of second-line chemotherapy using different regimens with mixed results. In three patients who had relapses following therapy with a regimen of combination cisplatin, doxorubicin, vincristine, and cyclophosphamide, treatment  with cisplatin, etoposide, and ifosfamide resulted in stable disease in two patients.3 Only one other report of a response to salvage chemotherapy with the same regimen was noted in the medical literature. Kosmidis et al reported a case of unresectable invasive thymoma treated with radiotherapy with an 80% response but 4 months later there was disease progression. Local recurrence was treated with cyclophosphamide, doxorubicin, and vincristine, which produced a partial response. The patient refused further treatment against medical advice. Nine months later, the patient presented with renal and abdominal lymph node metastasis. This was treated with the same combination of drugs, again producing a significant improvement consisting of a more than 50% reduction in tumor bulk, noted both clinically and radiographically. The patient eventually had a relapse 9 months after reinitiation of chemotherapy and died of renal failure.