Cerebral metastases in non-seminomatous germ cell tumour patients undergoing primary high-dose chemotherapy.

BACKGROUND: Retrospective analysis of characteristics and outcome of germ cell tumour (GCT) patients with cerebral metastases (CM) undergoing high-dose chemotherapy (HD-CTX) or relapsing with CM. PATIENTS AND METHODS: Patients initially presenting with CM (N=50 pts) or at first relapse (n=19 pts) after primary HD-CTX (434 pts) were analysed. RESULTS: Patients with primary CM (N=50) had elevated ss-human chorion gonadotropin (ss-HCG) in 88% and lung metastases in 90%. Eighty six percent responded to HD-CTX and 40% underwent CNS radiotherapy. Forty four percent achieved long-term survival after primary and 16% after salvage treatment (60% in total). All patients relapsing with CM (n=19) presented initially with ss-HCG-elevation and pulmonary metastases. Treatment consisted of CTX in 78%, irradiation in 90% and surgery in 63%. Twenty six percent achieved long-term survival. CONCLUSION: An interdisciplinary approach of HD-CTX, radiotherapy and surgery leads to long-term survival in 60% of patients with CM at initial diagnosis and 26% relapsing with CM.

Adjuvant chemoradiation using 5-fluorouracil/folinic acid/cisplatin with or without paclitaxel and radiation in patients with completely resected high-risk gastric cancer: two cooperative phase II studies of the AIO/ARO/ACO.

BACKGROUND: The current two studies evaluate the feasibility, toxicity and efficacy of an adjuvant combined modality treatment strategy containing a three to four-drug chemotherapy regimen plus 5-fluorouracil (FU)-based radiochemotherapy. PATIENTS AND METHODS: Between December 2000 and October 2003, a total of 86 patients were included in both studies. Patients with completely resected gastric adenocarcinoma including a D1 or D2 lymph node dissection (LND) were eligible. Treatment consisted of two cycles of folinic acid 500 mg/m2, 5-FU 2000 mg/m2 continuous infusion over 24 h once weekly for 6 consecutive weeks, paclitaxel 175 mg/m2 in weeks 1 and 4 and cisplatin 50 mg/m2 in weeks 2 and 5 (FLPP; n=41) or two cycles of the same 5-FU/folinic acid schedule but with cisplatin 50 mg/m2 only in weeks 1, 3 and 5 (FLP; n=45). Radiation with 45 Gy plus concomitantly applied 5-FU 225 mg/m2/24 h was scheduled in between the two cycles. RESULTS: Patients characteristics were: D1/D2 LND FLP group 53%/42%; FLPP group 27%/68%; stage distribution: UICC stages III/IV(M0) FLP group 63% and FLPP group 66%. Median follow-up was 10 months (3-25) for FLP and 18 months (2-51) for FLPP patients. CTC grade 3/4 toxicities during the first cycle/chemoradiation/second cycle of FLP: granulocytopenia 3%/0/27%, anorexia 6%/10%/8%; diarrhea 8%/0/4%, nausea 3%/0/4%; FLPP: granulocytopenia 0/0/37%, anorexia 5%/11%/6%; diarrhea 5%/0/3, nausea 3%/8%/0%; early death in one patient due to Pneumocystis carinii pneumonia. Projected 2-year progression-free survival was 64% (95% CI 56% to 68%) for the FLP and 61% (95% CI 42% to 78%) for the FLPP group. CONCLUSIONS: Both chemoradiation regimens appear feasible with an acceptable toxicity profile indicating that cisplatin can be added to 5-FU/FA and that even a four-drug regimen can be investigated further in prospective clinical trials in completely resected gastric cancer patients. Treatment should be given in experienced centres in order to avoid unnecessary toxicity.

Secondary leukemia after first-line high-dose chemotherapy for patients with advanced germ cell cancer.

PURPOSE: We investigated the incidence of secondary leukemia in patients treated with first-line high-dose 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 HD-VIP 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/m(2) (range, 2.2-9.4 g/m(2)). 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.

First-line sequential high-dose VIP chemotherapy with autologous transplantation for patients with primary mediastinal nonseminomatous germ cell tumours: a prospective trial.

To determine the efficacy of first-line sequential high-dose VIP chemotherapy (HD-VIP) in patients with primary mediastinal nonseminomatous germ cell tumours (GCT), 28 patients were enrolled on a German multicentre trial. High-Dose VIP chemotherapy consisted of 3-4 cycles of dose-intensive etoposide and ifosfamide plus cisplatin, q22days, each cycle followed by autologous peripheral blood stem cell transplantation plus granulocyte-colony stimulating factor (G-CSF) support. One cycle of standard-dose VIP was applied to harvest peripheral blood stem cells. Ten patients had mediastinal involvement as the only manifestation (36 %), 18 of 28 patients had additional metastatic sites, such as lung (n=17; 61%), liver (n=7; 25%), bone (n=5; 18%), lymph nodes (n=3; 11%) and CNS (n=3; 11%). Median follow-up was 43 months (range, 7-113) for all patients and 52 months (range, 22-113) for surviving patients. Nineteen of 28 patients obtained a disease-free status; 11 with HD-VIP alone and eight with adjunctive surgery. In addition, one of the four patients with marker negative partial remission after HD-VIP without resection of residual masses is currently alive. Two patients developed recurrence of GCT or teratoma. Two patients have died due to an associated haematologic disorder. The 2-year progression-free survival and overall survival rates are 64 and 68%, respectively. This report represents a subgroup analysis of 28 patients with mediastinal nonsemina within the German first-line study for 'poor prognosis' GCT. Compared to data of an international database analysis including 253 patients with mediastinal nonseminoma treated with conventional chemotherapy, the results may indicate that HD-VIP results in an approximately 15% survival improvement.

A phase I study of oral uracil-ftorafur plus folinic acid in combination with weekly paclitaxel in patients with solid tumors.

INTRODUCTION: Ftorafur is an orally available prodrug of 5-fluorouracil (5-FU). Its combination with uracil in a molar ratio of 1:4 (UFT) increases the 5-FU concentration in tumor cells compared with ftorafur alone. Paclitaxel has a broad spectrum of activity against solid tumors and synergic effects with UFT have been demonstrated in vitro. A phase I study was performed to determine the maximum tolerated dose of the combination of UFT and paclitaxel in patients with advanced solid tumors. STUDY DESIGN: UFT and folinic acid were applied at 300 mg/m2/day and 90 mg/day, respectively, on days 1-28, repeated on day 36. Paclitaxel was applied on days 1, 8, 15 and 22 of each cycle. The starting dose of paclitaxel was 50 mg/m2 and escalation in 10 mg/m2 steps was performed up to 100 mg/m2 weekly. RESULTS: Forty-seven consecutive patients with various solid tumors have been included in six different dose levels. One hundred and thirty cycles have been applied. The treatment was well tolerated overall. Most frequently encountered adverse effects were gastrointestinal and hematological toxicity (diarrhea CTC 3/4 in 6% of patients, anemia in 11%, leukocytopenia in 9%, polyneuropathy in 9%, fatigue in 11%, other in 6%). Partial remissions were observed in 28% of patients. CONCLUSION: Owing to the lack of overlapping toxicities, UFT/folinic acid plus paclitaxel can be combined at doses of proven single agent activity. Side effects are mainly attributable to the gastrointestinal toxicity of UFT and to the neuro- and hematotoxicity of paclitaxel. The recommended doses for phase II studies are 300 mg/m2 of UFT plus 90 mg of folinic acid on days 1-28, and 90 mg/m2 of paclitaxel weekly.