Pixantrone: a promising drug in the treatment of non-Hodgkin lymphomas.

Pixantrone (BBR2778) is a novel anthracycline derivative, manufactured by Cell Therapeutics Incorporated, WA, USA. In both preclinical and clinical studies pixantrone exhibited a significantly lower cardiac toxicity and better activity than that observed with alternative anthracyclines, as it is devoid of the putative cardiac toxicity generating 5,8-dihydroxy groups. With single-agent pixantrone, neutropenia was the dose-limiting toxicity. In relapsed aggressive non-Hodgkin lymphomas, weekly single-agent pixantrone 85 mg/m(2) for 3 weeks every 4 weeks was associated with a 27% overall response rate and a 15% complete response rate. When used in combination with chemotherapy regimens overall response rates of 58-74% and complete response rates of 37-57% were achieved.

Small-cell lung cancer: 8 years experience of a single multidisciplinary team.

Aims. We have audited the changes in treatment practice for small-cell lung cancer (SCLC) presented to a single multidisciplinary team (MDT) at Doncaster and Bassetlaw Hospitals between January 1998 and December 2005. Materials and Methods. The MDT database was used to identify all patients with SCLC. Anonymised demographic, treatment, and outcome details were extracted from the database supplemented by patient records. Results. 235 patients were identified. 112 (48%) had limited disease at presentation. Chemotherapy was the initial treatment for 195 patients, 77% of whom had a documented radiological response with a complete response in 24%. Chemotherapy regimes evolved during the study period with the increasing use of platinum-based chemotherapy. Anthracycline-based chemotherapy was most used before 2004 and was given to 57% of all patients. 42% received consolidation thoracic radiotherapy and 24% prophylactic cranial irradiation. The median and 2-year survival were 8 months and 18%, respectively, for patients with limited disease and 5 months and 5%, respectively, for extensive disease. Conclusion. We have documented changes in treatment practice and service delivery of SCLC over the 8 years during which the MDT has been operating. However, there has not achieve any significant improvement in outcome for the population of patients with SCLC.

Pixantrone: a novel aza-anthracenedione in the treatment of non-Hodgkin's lymphomas.

Pixantrone (BBR-2778) is a novel mitoxantrone-like drug, which lacks the 5,8-dihyroxy substitution groups thought to be responsible for the cardiac toxicity associated with mitoxantrone. In Phase I/II single-agent pixantrone clinical trials, neutropenia was the dose-limiting toxicity and the maximum tolerated dose was 150 mg/m(2)/week for 3 weeks every 4 weeks. In relapsed aggressive non-Hodgkin's lymphomas, weekly single-agent pixantrone 85 mg/m(2) for 3 weeks every 4 weeks was associated with a 27% overall response and a 15% complete response. When intensively pretreated patients with relapsed aggressive non-Hodgkin's lymphoma were treated with a cyclophosphamide, pixantrone, vincristine and prednisolone regimen (pixantrone substituted for doxorubicin in standard regimen [cyclophosphamide, doxorubicin, vincristine and prednisolone regimen (CHOP)]), the overall response was 74% and complete response 57%. In the BBR-2778, methylprednisolone, cisplatin and cytosine arabinoside (BSHAP) regimen, 58% overall response and 37% complete response were achieved. A number of randomised studies of pixantrone (BBR-2778) in patients with relapsed indolent or aggressive lymphomas are ongoing.

Treatment of metastatic gestational trophoblastic neoplasia.

Treatment of persistent gestational trophoblastic neoplasia (GTN) has been one of the success stories of modern day chemotherapy; however, occasional patients with metastatic disease still die. A potential difficulty in assessing published studies is that patient groups can be selected for treatment differently according to how risk categories are defined. The involvement of a specialist team from the outset is essential. Patients with low-risk metastatic GTN are treated successfully with single-agent chemotherapy using methotrexate or dactinomycin. Patients with high-risk metastatic disease receive combination chemotherapy regimens from the start. Worldwide experience has been accrued by use of regimens devised and tested by large centres. The high response rate and good long-term survival, as well as the tolerable acute and cumulative toxic effects, associated with use of etoposide, methotrexate and dactinomycin, alternating with cyclophosphamide and vincristine, make this protocol, or one of its variants, the current initial treatment of choice for patients. In view of the success of these regimens difficulty would be encountered in mounting a worthwhile randomised controlled trial; however, further well-designed studies are needed of novel approaches in very-high-risk and multiresistant disease.

High-dose chemotherapy with haematopoietic stem-cell support in patients with poor prognosis, relapsed or refractory germ cell tumours.

OBJECTIVE: To report our experience of high-dose chemotherapy (HDC) with haematopoietic stem-cell support (HSC) in patients with poor risk, relapsed or refractory germ cell tumours (GCTs), as this treatment might offer effective salvage for patients with disseminated GCTs. PATIENTS AND METHODS: We retrospectively reviewed the medical records and database for 33 patients with GCT who were treated with HDC with HSC in our centres. RESULTS: Thirty-three patients were treated with either one or two cycles of carboplatin and etoposide-based HDC with HSC support, between March 1990 and October 2003. Twenty-six patients (79%) had nonseminomatous GCT, six seminoma (18%), and one (3%) a combined seminoma and teratoma. Twenty patients (60%) had previously had a clinical complete response after previous chemotherapy +/- surgery for residual disease. Most patients were treated with HDC for relapsing (49%) or relative refractory disease (30%), but seven (21%) had HDC in the first partial remission. The complete response rate to HDC was 58%. There were two treatment-related deaths (6%). As of April 2005, 18 patients were alive and disease-free with a median (range) follow-up of 72 (0.5-174) months. The 5-year overall and progression-free survival probabilities were 57% and 56%, respectively. The median (range) times to absolute neutrophil count recovery (> or = 500/microL) were 13 (9-24) and 12 (10-15) days, and for platelet count recovery ( > or = 20,000/microL) were 16 (7-50) and 13 (11-17) days, in the first and second cycles, respectively. CONCLUSION: The role of HDC with HSC support in metastatic GCTs remains controversial, and data from randomized controlled trials are needed. Our experience suggests that, in selected patients, this approach might be a useful form of salvage therapy.