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Purpose: We investigated the incidence of secondary leukemia in patients treated with first-line highdose chemotherapy (HDCT) plus autologous stem cell transplantation (PBSCT) for advanced testicular cancer. Methods: Three hundred and twenty-three patients who were entered into two consecutive prospective Phase-II studies of the German Testicular Cancer Study Group were analyzed. A total of 221 patients had received HDVIP containing cisplatin, ifosfamide, and etoposide and 102 patients were treated with Tax-HD-VIP containing cisplatin, ifosfamide, etoposide, and paclitaxel, each cycle supported by autologous PBSCT. Results: Patients had received a median cumulative etoposide dose of 4.9 g/m2 (range, 2.2–9.4 g/m2). The median follow-up duration for all patients was 36 months (range, 0–128) with a median follow up time of 50 months (range, 0–128) for patients surviving at least 1 year after therapy. One patient developed a secondary acute myeloid leukemia (s-AML) involving a chromosomal translocation t(11;19)(q23;p13.3) 24 months after the start of chemotherapy resulting in a cumulative incidence of 0.48% [95% confidence interval (CI) 0–1.42]. Additionally, two patients with primary mediastinal germ cell cancer developed a myelodysplastic syndrome. No solid tumors had occurred. Conclusions: HDCT including high-dose etoposide with autologous PBSCT as first-line therapy for advanced testicular cancer was associated with an acceptably low risk of developing secondary leukemia. [ABSTRACT FROM AUTHOR]

The aim of this study was to define the maximum tolerated dose (MTD) of bolus mitomycin C (MMC) in combination with 24?h-continuous infusion of 5-flourouracil (FU) plus folinic acid, and to assess the toxicity and activity in patients with previously treated colorectal and gastric cancer. Escalating doses of MMC starting from 6?mg?m-2 in 2?mg?m-2-steps to a maximum of 10?mg?m-2 were applied on days 1 and 22, given to fixed doses of 5-FU (2.600?mg?m-2) as 24?h infusion and folinic acid 500?mg?m-2 prior to 5-FU weekly for 6 weeks. At least three patients were treated at each dose level. A total of 16 patients have been included in the phase I study. At the highest dose level (MMC 10?mg?m-2), grade III thrombocytopenia, dyspnoea, mucositis and diarrhoea were observed in one patient each (17 %). In the phase II study 45 patients, 33 with colorectal cancer and 12 with gastric cancer, 23 patients after failure of first- and 22 patients after at least second-line or subsequent chemotherapy have been treated. Seven partial responses (PR) were registered (16%), one (3%; CI95%, 0-16) in colorectal and six (50%; CI95%, 21-79%) in gastric cancer patients. In all, 17 (38%) achieved disease stabilisation, 15 colorectal (45%, CI95%, 28-64%) and two gastric cancer patients (17%; CI95%, 2-48%). The median progression-free survival was 3.1 months (range, 0.9-9.1) in colorectal and 4.6 months (range, 0.7-12.4) in gastric cancer. The median overall survival time was 6.6 months (range, 1.9-15.6) in colorectal and 7.1 months (range, 1.7-20.8) in patients with gastric cancer. This regimen was considered to be safe and well tolerated for pretreated patients with gastrointestinal adenocarcinoma. In gastric cancer,MMC plus infusional 5-FU/folinic acid may be a potential second-line regimen with promising antitumour activity.British Journal of Cancer (2003) 89, 2051-2056. doi:10.1038/sj.bjc.6601412 www.bjcancer.com [ABSTRACT FROM AUTHOR]

First-line sequential high dose chemotherapy is under investigation in patients with "poor prognosis" metastatic germ cell tumours in order to improve survival. Despite the use of autologous peripheral blood stem cell transplantation and granulocyte colony stimulating factor chemotherapy dose intensification is associated with severe haematotoxicity including anaemia, which may significantly affect quality of life and tolerability of chemotherapy. This study investigates the frequency and degree of anaemia in patients receiving first-line sequential high dose chemotherapy for metastatic testicular cancer and the impact of anaemia on treatment outcome. A total of 101 newly diagnosed patients with "poor prognosis" metastatic nonseminomatous germ cell tumours were treated with one cycle of standard VIP followed by three cycles of HD-VIP-chemotherapy (etoposide, ifosfamide, cisplatin) within a large phase I/II study. Differential blood cell counts were taken prior, during and after every cycle of chemotherapy. Additionally, the numbers of red blood cell and platelet transfusions were recorded. Kaplan-Meier analyses were performed to correlate pre-treatment and post-treatment haemoglobin values to response and overall survival. Forty-eight per cent of the patients were classified anaemic (haemoglobin <12 g dl(-1)) prior to the start of chemotherapy. The application of sequential HD-VIP resulted in median haemoglobin nadirs between 7.8 g dl(-1) (range 5.5-11.1 g dl(-1)) in the first cycle and 7.6 g dl(-1) (range 6.0-11.4 g dl(-1)) in the third cycle despite the frequent use of red blood cell transfusions. Almost all patients (99%) had haemoglobin levels <10 g dl(-1) at some timepoint during first-line sequential high dose chemotherapy. Overall, 97 patients received red blood cell transfusions with a median of 10 units (range 2-25) per patient during the four consecutive cycles of therapy. The time to first transfusion was shortest in patients with the lowest initial haemoglobin values. While there was no prediction of response or outcome by baseline haemoglobin-levels, a significant survival difference in favour of patients with a haemoglobin value >10.5 g dl(-1) after completion of four cycles of therapy (at leukocyte recovery after the last cycle) compared to those with haemoglobin values <10.5 g dl(-1) was found with 3-year overall survival rates of 87% vs 68%, respectively (P<0.05). Severe anaemia is a very frequent side effect of sequential dose intensive therapy in patients with germ cell cancer, with almost all patients becoming transfusion dependent. Despite the frequent use of red blood cell transfusions, median haemoglobin nadirs remained about 7.5-8 g dl(-1) during therapy. A correlation of haemoglobin-values after completion of therapy to overall treatment outcome was found. [ABSTRACT FROM AUTHOR]

Testicular germ cell tumours are a highly curable malignancy even in the presence of metastases, with an overall survival rate of approximately 90 to 95% when all stages are considered. Current therapeutic strategies aim at risk-adapted therapy, trying to maintain favourable overall results while reducing treatment-related toxicity, particularly in non-advanced disease. In stage I disease, unilateral inguinal orchiectomy represents the standard diagnostic and therapeutic approach. For patients with clinical stage I seminoma, prophylactic para-aortic radiotherapy with 26Gy is commonly employed. In patients with nonseminomatous germ cell tumours (NSGCT) at clinical stage I, the 3 options are: (i) retroperitoneal lymphadenectomy; (ii) a wait-and-see strategy; or (iii) 2 cycles of adjuvant chemotherapy. The individual risk profile for tumour recurrence, mainly based on histopathological criteria such as vascular tumour invasion, should guide treatment decisions in this group of patients. Radiotherapy is still the standard approach in clinical stage IIA/B seminoma, whereas in patients with a low tumour burden of NSGCT, retroperitoneal lymphadenectomy is frequently used followed by surveillance or adjuvant chemotherapy. Primary chemotherapy in these stages of disease may be at least equally successful. Major progress has also been achieved in the treatment of NSGCT patients with metastatic disease greater than clinical stage IIB, for whom primary chemotherapy represents the standard approach. After cisplatin-based combination chemotherapy, between 70 and 90% of patients will achieve a durable remission. In patients with ‘good risk’ metastatic disease, 3 cycles of cisplatin, etoposide and bleomycin (PEB) remain the standard treatment, despite several randomised trials trying to avoid the lung-toxic bleomycin or substituting cisplatin by carboplatin. In patients with ‘intermediate’ and ‘poor prognosis’ disease, 4 cycles of PEB given at 3-week intervals are considered routine treatment. The role of high dose chemotherapy with peripheral autologous blood stem cell transplantation is currently being investigated for patients presenting initially with advanced (poor prognosis) metastatic disease and for patients with relapse after previous chemotherapy, in whom conventional-dose salvage regimens will only result in 20% long-term survival. Because of the large group of patients with metastatic disease being cured, the possible long-term adverse effects of treatment have become important. Only a slightly elevated risk for therapy-related secondary malignancies has been identified. Long-term adverse effects associated with cisplatin may affect a larger proportion of patients. Further research should focus on reducing the risk of chemotherapy-related chronic toxicity. [ABSTRACT FROM AUTHOR]