The prognosis of high-grade oligodendroglioma has been reported poor with an average survival of approximately 17 months. Local recurrence after surgery is seen in about 50% of the patients, but distant extracranial metastases have been described rarely. Frequent extracranial metastases have been reported in the lungs, pleura, lymph nodes, bones, liver, adrenal glands, kidneys and other sites. We present a case of 16-year-old girl with high-grade oligodendroglioma who developed bilateral pulmonary metastases 19 months following complete resection of the primary brain tumor. She did not respond to first-line chemotherapy; however, the patient achieved an almost complete response with cisplatin (CDDP) and etoposide (VP-16) salvage chemotherapy. She remains well and asymptomatic 18 months after the end of chemotherapy. We herein review the literature and discuss all the possible mechanisms for extracranial dissemination of primary brain tumours.

Cisplatin (CDDP), epirubicin (EPI) and docetaxel have single agent activity against urothelial transitional cell carcinoma (TCC). We evaluated the efficacy and toxicity of this combination in locally advanced or metastatic urothelial TCC. Patients with urothelial TCC who had no prior chemotherapy (prior adjuvant chemotherapy > 6 months allowed) were eligible for entry the study. Eligibility criteria were performance status 0-3, granulocyte count (AGC) > or = 1.5 (10(9)/l), platelet count > or = 100 (10(9)/l), clearance creatine > or = 60 ml/min and total bilirubin level < or = 1.5 mg/dl. Treatment consisted of EPI 40 mg/m2 intravenous push, docetaxel 75 mg/m2 in 1 h infusion with premedication and CDDP 75 mg/m2 with pre- and posthydration. Treatment was repeated every 21 days. Antiemetics with dexamethasone and 5-HT3 antagonists were used routinely. Prophylactic haematopoietic growth factors were not used. Patients were evaluated for toxicity weekly and assessed for response every two cycles of treatment. 32 patients were entered into the study and 30 patients (7 with locally advanced and 23 with metastatic disease) were assessable for response. There were 9 (30.0%) complete responses (2, 28.6% in locally advanced and 7, 30.4% in metastatic disease) and 11 (36.7%) partial responses (3, 42.9% in locally advanced and 8, 34.8% in metastatic disease) with an overall response rate (RR) of 66.7% (71.5% in locally advanced, 65.2% in metastatic disease). Overall median survival was 14.5 months (15 months for locally advanced, 12.5 months for metastatic disease). The median duration of response in patients with metastatic disease was 8.5 months. 16 (53.3%) patients required one dose reduction and 5 (16.7%) patients required two dose reductions for a nadir AGC < or = 500/mm3. Four episodes of febrile neutropenia and sepsis occurred. No patient had a dose reduction or treatment delay for any other grade 3/4 toxicity. There were no treatment delays due to myelotoxicity. Alopecia was universal. Non-haematological toxicity including mucositis, fluid retention, allergy, cutaneous toxicity, diarrhoea and neurotoxicity were mild and infrequent. The combination of EPI, docetaxel and CDDP is an active regimen for urothelial TCC. The response rate and toxicity were comparable with the M-VAC (methotrexate, vinblastine, doxorubicin, cisplastin) regimen. Phase III trials comparing this regimen with M-VAC are warranted.

Testicular non-Hodgkin’s lymphoma is an uncommon disease and its outcome following chemotherapy and/or radiotherapy has been variable. A retrospective analysis was performed on 26 patients with primary testicular lymphoma treated predominantly with anthracycline-based chemotherapy between 1984 and 1999. The patients’ median age was 60 years (range 19–82 years) with 17 (65.4%) patients being older than 60 years. Four (15.4%) patients had constitutional B symptoms. There were 11 (42.3%) patients with high grade lymphoma, 12 (46.2%) with intermediate grade, 1 (3.8%) with low grade and 2 (7.7%) were not classified. According to the Ann-Anbor staging system, 18 patients (69.2%) had early (stage I/II) and 8 (30.8%) advanced (stage III/IV) disease. Chemotherapy was administered to 24 patients including 22 patients who received anthracycline-based chemotherapy. Two stage IEA patients were treated with orchidectomy and adjuvant radiotherapy to the regional lymph nodes without systemic chemotherapy. Chemotherapy alone resulted in a complete remission (CR) in 14 (58.3%) of 24 patients and partial remission in 1 (4.2%), amounting to an overall response rate (RR) of 62.5%. Of the 5 stage I patients who had chemotherapy on an adjuvant basis, 4 (80%) had CR/no evidence of disease. Of the 11 stage II patients, 8 (72.7%) achieved CR and 1 (9.1%) PR (overall RR of 81.8%). CR was obtained in 2 (25%) of 8 stage III/IV patients. Both patients remain disease free for 26 and 65 months. Excluding the 5 stage I patients, chemotherapy resulted in a CR in 10/19 (52.6%) patients and a PR in 1/19 (5.2%), inducing an overall RR of 57.8%. The mean duration of response was 75 months (range 8–145.5+ months). After a median follow-up of 87 months (range 0.13–145.5+ months) the median survival time was 31 months (range 0.13–145.5+ months) and the median time to progression (TTP) 17 months (range 0.13–145.5+ months). The median TTP was significantly higher in early disease compared to that of advanced disease (52 vs. 3 months, p = 0.02). Of the 3 patients who relapsed following disease-free status, CNS involvement occurred in 2 stage II patients and contralateral testis involvement in 1 stage IEA, respectively. The latter remained disease free for 2 years following orchidectomy alone. The other 2 patients who relapsed did not respond to salvage chemotherapy and died. There was no significant relationship between the values of LDH and β2-microglobulin with the outcome except for ESR which was significantly related with the CR (p = 0.005) or RR (p = 0.005). In conclusion, patients with primary testicular lymphoma have a poor outcome, despite the treatment with anthracycline-containing regimens. Treatment with anthracycline-based chemotherapy is recommended in patients at early stages. In advanced disease, more intensive or investigational regimens should be considered. Because the relapse rate in the CNS and contralateral testis is quite high in most studies, prophylactic CNS treatment and radiotherapy to the other testis should be included in the management of testicular lymphoma.

PURPOSETo evaluate the efficacy and toxicity of the combination of carboplatin, docetaxel, and gemcitabine in patients with advanced non-small-cell lung cancer (NSCLC).PATIENTS AND METHODSForty-five chemotherapy-naive patients with NSCLC were treated on an out-patient basis with carboplatin area under the curve 5 intravenous (IV) and gemcitabine 800 mg/m(2) IV on day 1 and docetaxel 75 mg/m(2) IV and gemcitabine 800 mg/m(2) IV on day 8. Granulocyte colony-stimulating factor (150 ug/m(2) subcutaneously) was given prophylactically from day 3 to day 6 and day 10 to day 16. Chemotherapy was repeated every 4 weeks. Patients were evaluated for response every two cycles of treatment.RESULTSThe median age of the patients was 58 years (range, 24 to 75 years). The performance status was 0 for 16 patients, 1 for 17 patients, and 2 for 12 patients. Nine patients (20%) had stage IIIB disease, and 36 (80%) had stage IV; histology was mainly squamous cell carcinoma (51.2% of patients) that was poorly differentiated (37.8%). All 45 patients were assessable for toxicity, and 41 were assessable for response. On an intent-to-treat analysis, the objective response rate was 46. 5% (21 out of 45 patients; 95% confidence interval [CI], 31.7% to 62. 5%). Of the 45 patients, four (8.8%) achieved a complete response (95% CI, 2.5% to 21.2%); 17 (37.7%) achieved a partial response (95% CI, 23.8% to 53.5%); seven (15.5%) had stable disease; and 14 (31. 1%) had progressive disease. The median survival time was 13.5 months, and the actuarial 1-year survival rate was 51.11%. The median duration of response was 7.6 months, and the time to tumor progression was 8.1 months. Grade 3/4 anemia and thrombocytopenia occurred in 17.7% and 28.8% of patients, respectively. Twenty-one patients (46.6%) developed grade 3/4 neutropenia, and six patients (13.3%) were complicated with fever. Alopecia was universal. Grade 3 diarrhea occurred in four patients (8.8%); grade 3/4 neurotoxicity occurred in 10 patients (22.2%); and grade 2/3 allergic reaction occurred in three patients (16.6%). There were no treatment-related deaths. Six patients (13.3%) required a dose reduction, two of which required two reductions.CONCLUSIONSThe combination of carboplatin, docetaxel, and gemcitabine is an effective regimen for the treatment of chemotherapy-naive patients with advanced NSCLC, causing only moderate toxicity.

Extragonadal germ cell tumours (EGCT) are uncommon, most frequently arise in the mediastinum and retroperitoneum and have variable responses to platinum-based chemotherapy. A retrospective analysis was performed on 38 patients with EGCT treated with cisplatin-based (CDDP) or carboplatin-based (CBDCA) chemotherapy between 1984 and 1998. Twenty-four patients had nonseminomatous germ cell tumours (NSGCT) and 14 seminoma. Twenty-two tumours arose in the mediastinum (13 nonseminomas, 9 seminomas) and 16 in the retroperitoneum (11 NSGCT, 5 seminomas). Initial surgery included complete resection in 1 patient, biopsy in 27 patients and debulking surgery in 10 patients. Complete response rates with chemotherapy +/- surgery were as follows: mediastinum 14 of 21 (66.66%) patients (8 of 12-75% NSGCT, 6 of 9-66.66% seminomas) and retroperitoneum 14 of 16 (87.5%) patients (9 of 11-81.81% NSGCT, 5 of 5-100% seminomas). One patient who underwent complete resection of a mediastinal malignant teratoma combined, received PVB chemotherapy on an adjuvant basis and remains alive and disease-free. Three additional seminoma patients who achieved partial response after chemotherapy remain alive and disease-free following mediastinal radiotherapy. All 14 patients with extragonadal seminomas remain alive with no evidence of disease at a median follow-up of 49 months (range 7-164), giving an overall survival of 100%. Nine of 13 (69.23%) patients with mediastinal NSGCT are long-term disease-free at a median follow-up of 43.5 months (range 7-152). Nine of 11 (81.81%) patients with retroperitoneal NSGCT remain alive and disease-free at a median follow-up of 56 months (range 14-110). Complete surgical resection of residual mass was undertaken in 10 patients (3 seminomas, 7 nonseminomas). The histology revealed necrosis/fibrosis in 6 patients (3 seminomas, 3 NSGCT) and viable cancer in 4 patients. Patients who had viable malignant cells in the resected specimens received two more courses of VelP chemotherapy. None of our patients had relapsed at the time of this analysis. None of our 6 patients who underwent testicular biopsy (1 patient) or orchiectomy (5 patients) due to suspicious ultrasound of the testis were found to have testicular tumour or fibrotic scar. In conclusion, this retrospective analysis showed significant responses in patients with either mediastinal or retroperitoneal NSGCT treated with CDDP- or CBDCA-based chemotherapy +/- surgery. All patients with extragonadal seminomas remain alive with no evidence of disease, regardless of the site at presentation.