Advances in our understanding of the biology, new diagnostic approaches and recent treatment strategies for testicular germ cell cancer.
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Germinoma↗
Biomedical subjects
C Bokemeyer
Publications and source records attributed to C Bokemeyer.
The role of high-dose chemotherapy in relapsed germ cell tumors.
Overall, patients with relapsed or progressive germ cell tumors after cisplatin-based chemotherapy have a low chance of cure. Using conventional-dose chemotherapy (CDCT) as salvage treatment, only 15-30% of the patients will become long-term survivors. It is well known that the majority of these patients will ultimately die of their disease. Therefore, improvement of the standard treatment is clearly desirable. In the last years, high-dose chemotherapy (HDCT) has been established as an effective salvage modality. A matched-pair analysis showed an advantage for HDCT compared with CDCT with an improvement in event-free and overall survival. Furthermore, due to increasing clinical experience in the management of side-effects, the use of peripheral blood progenitor cells and the availability of hematopoietic growth factors, HDCT has become relatively safe. Therefore, HDCT should be administered in patients with first relapse and unfavorable prognostic factors, and as second or subsequent salvage treatment followed by complete resections of tumor residuals. Patients with relapse or progressive disease after HDCT who do not qualify for desperation surgery could be salvaged with palliative chemotherapy combinations using gemcitabine, oxaliplatin and paclitaxel. This report reviews the current treatment strategies and recent developments with respect to HDCT given as salvage treatment and discusses the role of prognostic factors in the management of such situations.
Antineoplastic Agents↗
Combination chemotherapy with gemcitabine plus oxaliplatin in patients with intensively pretreated or refractory germ cell cancer: a study of the German Testicular Cancer Study Group.
PURPOSE: Long-term survival is rarely achieved in patients with cisplatin-refractory germ cell cancer (GCT). Both single-agent gemcitabine and oxaliplatin have shown activity in patients who experience relapse or are refractory to cisplatin treatment. This study investigates the activity of a gemcitabine plus oxaliplatin regimen in these patients. PATIENTS AND METHODS: Gemcitabine was administered at a dose of 1,000 mg/m(2) on days 1 and 8; oxaliplatin was administered at a dose of 130 mg/m(2) on day 1. Response was evaluated every 4 weeks. RESULTS: Thirty-five patients with a median age of 37 years (range, 21 to 54 years) were enrolled onto the study. Primary tumor localization was gonadal, retroperitoneal, or mediastinal in 30, one, and four patients, respectively. Patients had been pretreated with a median of six platinum-containing cycles (range, four to 13 cycles) and 89% of patients previously had experienced treatment failure after high-dose chemotherapy with peripheral-blood stem-cell transplantation. Sixty-three percent of patients were considered absolutely cisplatin-refractory or cisplatin-refractory. A median of two cycles (range, 1 to 6 cycles) per patient were applied. Toxicity consisted mainly of myelosuppression, with Common Toxicity Criteria grade 3 occurring in 54% of patients. Only 9% of patients developed neutropenic fever. Three patients attained a complete remission (CR), two patients attained a marker-negative partial remission, and 11 patients attained a marker-positive partial remission, resulting in an overall response rate of 46% (95% CI, 30% to 64%). All three patients with CR and one patient with a marker-negative partial remission remained disease free at 16+, 12+, 4+, and 2+ months of follow-up. Seven (44%) of these 16 responses, including one CR, occurred in cisplatin-refractory patients. CONCLUSION: Gemcitabine plus oxaliplatin demonstrates antitumor activity with acceptable toxicity in heavily pretreated patients with relapsed or cisplatin-refractory GCT, and may offer a chance of long-term survival for selected patients.
Adult↗
[Chemotherapy for germ cell cancer].
Chemotherapy for germ cell cancer is usually indicated in patients who present with metastatic disease, suffer relapses, or progress after their initial treatment. Rarely is chemotherapy needed in the palliative treatment of refractory patients. However, more recently chemotherapy has been demonstrated to benefit also patients with early stages of seminoma as well as nonseminoma. Therefore, the most recent European consensus guidelines on treatment and diagnosis of germ cell cancer list chemotherapy as an alternative treatment option in the early tumor stages I and II. The application of chemotherapy represents a challenge for both patients and the treating physician who must be experienced with a broad array of chemotherapy regimens and competent in their application. Particularly the treatment of patients with advanced tumor stages requires good clinical skills on the part of the treating oncologist. If excessive toxicity is to be avoided and a curative treatment option maintained, overtreatment as well as undertreatment are notorious pitfalls.
Antineoplastic Agents↗
Late relapse after treatment for nonseminomatous testicular germ cell tumors according to a single center-based experience.
The introduction of cisplatin-based systemic chemotherapy into the clinical routine has resulted in a substantial improvement of the recurrence-free and long-term survival of patients with metastatic testicular germ cell tumors. Late relapses after the completion of first-line therapy, comprising systemic chemotherapeutic treatment in combination with a complete resection of residual tumor masses visible in about 25-50% of patients, have been reported to occur in 1-5% of patients later than 2 years following the initial treatment. It has been reported that the risk for the development of late recurrence is correlated to the tumor burden at first diagnosis and/or the presence of teratomatous components within the primary testicular cancer. Second-line chemotherapy in combination with surgery, although not very well standardized, has been recommended as the most effective therapeutic regimen during the treatment of patients suffering from late recurrent germ cell tumors. Herein, we report our single-center experience with 14 patients in different clinical stages who developed late relapse after successful first-line therapy. In the present series, the risk for late relapse was not correlated to the clinical stage at first diagnosis or the presence of teratomatous elements within the primary tumor. It became evident that in selected cases chemotherapy alone can be considered a curative treatment option.
Combined Modality Therapy↗
EORTC guidelines for the use of erythropoietic proteins in anaemic patients with cancer.
Anaemia is frequently diagnosed in patients with cancer, yet it is difficult to identify a single cause due to its multifactorial aetiology. We conducted a systematic literature review (1996-2003) to produce evidence-based guidelines on the use of erythropoietic proteins in anaemic patients with cancer (see ). Level I evidence exists for a positive impact of erythropoietic proteins on haemoglobin (Hb) levels when administered to patients with chemotherapy-induced anaemia or anaemia of chronic disease, when used to prevent cancer anaemia, in patients undergoing cancer surgery and following allogeneic bone marrow transplantation. The Hb level at which erythropoietic protein therapy should be initiated is difficult to determine as it varied between studies; a large number of Level I studies in patients with chemotherapy-induced anaemia or anaemia of chronic disease enrolled patients with a Hb concentration </=105 g/L, but none compared the effect of different baseline Hb levels on the response to treatment. Similarly, several studies defined the target Hb concentration as 120-130 g/L following treatment with erythropoietic proteins, but none specifically addressed the correlation between target Hb level and clinical benefit in a randomised fashion. Level I evidence shows that red blood cell (RBC) transfusion requirements are significantly reduced with erythropoietic protein therapy in patients with chemotherapy-induced anaemia or when used to prevent cancer anaemia (approximately 20% reduction compared with controls). We found indirect Level I and III evidence that patients with chemotherapy-induced anaemia or anaemia of chronic disease initially classified as non-responders to standard doses proceed to respond to treatment following a dose increase (absolute increases in response rate ranged from 8% to 18%). However, none of these studies examined the effect on response rates of a longer treatment period at the lower dose, or performed a randomised comparison of a dose increase versus an unchanged dose. There is Level I evidence to show that quality-of-life (QOL) is significantly improved in patients with chemotherapy-induced anaemia and in those with anaemia of chronic disease, particularly in patients achieving a Hb response to erythropoietic protein therapy. There are insufficient data to determine the effect on survival following treatment with erythropoietic proteins in conjunction with chemotherapy or radiotherapy. There is Level I evidence that dosing of erythropoietic proteins less frequently than three times per week (TIW) is efficacious when used to treat chemotherapy-induced anaemia or prevent cancer anaemia. There is Level III evidence that initial doses of erythropoietic proteins considered to be higher than current standard practice produce higher haematological responses in patients with chemotherapy-induced anaemia or anaemia of chronic disease. Level I evidence demonstrates that several baseline patient parameters (e.g., low endogenous erythropoietin [EPO] concentration, age <60 years, Hb concentration >/=90 g/L) impact upon the response to erythropoietic proteins when used to treat chemotherapy-induced anaemia or prevent cancer anaemia. Evidence indicates that endogenous EPO concentration impacts on response in patients with lymphoproliferative malignancies, but is not a valid parameter in patients with solid tumours. There is Level I evidence that fixed doses of erythropoietic proteins can be used at the start of therapy to treat patients with chemotherapy-induced anaemia, but maintenance doses should be titrated individually. There is no evidence that pure red cell aplasia (PRCA) occurs following treatment with erythropoietic proteins in patients with chemotherapy-induced anaemia or when used prophylactically in patients with cancer. There is Level I evidence that the risk of thromboembolic events and hypertension are slightly elevated in patients with chemotherapy-induced anaemia receiving erythropoietic proteins. Level I evidence supports the effectiveness of erythropoietic proteins to prevenroteins to prevent anaemia in non-anaemic cancer patients receiving chemotherapy or radiotherapy or in those undergoing cancer surgery. However, these are non-licensed indications and we do not currently recommend the prophylactic use of erythropoietic proteins to prevent anaemia in patients who have normal Hb values at the start of treatment. Additional trials are warranted, especially on the issues of iron replacement and cost-effectiveness of erythropoietic protein therapy, as well as on tumour response/progression and survival.
Anemia↗
[Early prediction of treatment response to high-dose chemotherapy in patients with relapsed germ cell tumors using [18F]FDG-PET, CT or MRI, and tumor marker].
PURPOSE: To assess the ability of [(18)F]FDG-PET, CT/MRI and serum tumor marker (TM) for the early prediction of response in patients with metastatic germ cell tumors (GCT) undergoing salvage high-dose chemotherapy (HD-CTX). MATERIALS AND METHODS: Before commencement of HD-CTX, 19 patients with metastases from GCT were evaluated with [(18)F]FDG-PET, CT or MRI and TM after 2-3 cycles of induction chemotherapy and the results compared with those of the baseline examinations. PET was analyzed visually and quantitatively by calculating the standard uptake value (SUV). CT or MRI was evaluated for changes in tumor size (progressive disease/stable disease PD/SD = viable lesion; partial remission/complete remission PR/CR = nonviable lesion), density or signal intensity, homogeneity and contrast enhancement. For the prognosis, the worse case, i.e., the most vital lesion detected in a patient, was considered. The reference standard was the result of the histology after resection of any residual masses (N = 10) and/or the clinical-radiological follow-up for at least 6 months after completion of the treatment (N = 9). RESULTS: Six of nineteen patients (32 %) remained progression-free for over 6 months following treatment, whereas 13 (68 %) progressed. The outcome of HD-CTX was correctly predicted by PET, CT and TM in 89 %, 67 % and 88 %, respectively. In 5 of 6 patients with successful HD-CTX, PET was negative (mean SUV = 1.8), with CT or MRI showing a partial regression of the tumor in 4 of 5 patients. Of the 13 patients not cured by HD-CTX, the PET data were positive in all (mean SUV = 2.7), and the CT/MRI results were true positive (PD or SD) in 8 and false negative (PR) in 5 patients. The combined assessment of CT and TM corrected 3 false negative prognoses and 1 false positive CT prognosis. Two patients with unfavorable outcome despite a favorable response by CT and TM criteria were exclusively identified by PET. The resultant sensitivities and specificities for the prediction of therapy response are as follows: PET 100% and 67%; CT/MRI 62% and 80%; TM 83% and 100%; CT+TM 85% and 83%. CONCLUSION: FDG-PET has a high prognostic value for predicting the response to chemotherapy in patients with metastatic GCT early in the course of treatment and may improve patient selection for subsequent HD-CTX protocols. Especially in patients with response to induction chemotherapy according to CT or TM evaluation, PET offers additional information to detect patients with an overall unfavorable outcome.
Adult↗
European consensus on diagnosis and treatment of germ cell cancer: a report of the European Germ Cell Cancer Consensus Group (EGCCCG).
Germ cell tumour is the most frequent malignant tumour type in young men with a 100% rise in the incidence every 20 years. Despite this, the high sensitivity of germ cell tumours to platinum-based chemotherapy, together with radiation and surgical measures, leads to the high cure rate of > or = 99% in early stages and 90%, 75-80% and 50% in advanced disease with 'good', 'intermediate' and 'poor' prognostic criteria (IGCCCG classification), respectively. The high cure rate in patients with limited metastatic disease allows the reduction of overall treatment load, and therefore less acute and long-term toxicity, e.g. organ sparing surgery for specific cases, reduced dose and treatment volume of irradiation or substitution of node dissection by surveillance or adjuvant chemotherapy according to the presence or absence of vascular invasion. Thus, different treatment options according to prognostic factors including histology, stage and patient factors and possibilities of the treating centre as well may be used to define the treatment strategy which is definitively chosen for an individual patient. However, this strategy of reduction of treatment load as well as the treatment itself require very high expertise of the treating physician with careful management and follow-up and thorough cooperation by the patient as well to maintain the high rate for cure. Treatment decisions must be based on the available evidence which has been the basis for this consensus guideline delivering a clear proposal for diagnostic and treatment measures in each stage of gonadal and extragonadal germ cell tumour and individual clinical situations. Since this guideline is based on the highest evidence level available today, a deviation from these proposals should be a rare and justified exception.
Europe↗
Elderly patients with acute myeloid leukaemia: characteristics in biology, patients and treatment. Recommendations of the Working Group Geriatric Oncology of the German Society for Haematology and Oncology (DGHO), the Austrian Society for Haematology and Oncology (OGHO) and the German Society for Geriatrics (DGG).
While the incidence rate of acute myeloid leukaemia (AML) is increasing with the age of the patients, the 5-year-survival rates are decreasing in an age-dependent manner. Patients with AML are considered to be old when they have reached the age of 60. This consideration is due to patient- and disease-specific parameters, which reveal differences between older and younger patients with AML. Standard of therapy is a dose-intensive chemotherapy aiming at the induction of complete remission, followed by different kinds of post-remission therapies. A small percentage of patients can be cured by this approach. However, most patients will die within the first 2 years after diagnosis due to resistance or relapse of the disease or therapy-related complications. The improvements achieved in the treatment of patients with AML are mainly restricted to the group of younger patients. The small percentage of patients who are cured, and the high rate of treatment-related mortality in elderly patients with AML give rise to the question which patients benefit from a primarily curative approach, and which should be treated with a palliative approach. The value of a palliative approach has not yet been consistently assessed in clinical trials. Geriatric assessment will be an important tool in clinical trials for elderly patients with AML to be used in the decision making process. There is hope that new classes of drugs and treatment modalities such as inhibitors of signal transduction, monoclonal antibodies, inhibitors of angiogenesis, or allogenic blood stem cell therapy after non-myeloablative conditioning regimens will improve the therapy of elderly patients with AML in the near future.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Chemotherapy in elderly patients with advanced lung cancer. Part I: General aspects and treatment of small cell lung cancer (SCLC).
There is much uncertainty whether chemotherapy is beneficial for elderly patients with advanced lung cancer. Whereas age alone is not an adverse prognostic factor, decline of physiological function and comorbidity can result in higher rates of treatment-related toxicity, in particular myelosuppression. The higher incidence of comorbid conditions, frequently sharing the risk profile of the malignancy, can translate into worse survival. Therefore, a geriatric assessment of the patient's overall situation should guide decision-making. Mainstay of treatment of small cell lung cancer (SCLC), also in the elderly, is combination therapy. Several retrospective analyses reveal that in elderly patients often lower drug doses are delivered. However, the treatment outcome of these patients does not appear to be worse compared to younger patients. For functionally independent elderly patients, combination chemotherapy with carboplatin and etoposide, supported by optimized supportive care, possibly including hematopoietic growth factors (G-CSF) to minimize toxicity, should be considered. Special attention to renal function should be given and individualized drug dosing, adapted to the glomerular filtration rate, is mandatory. For patients with some functional dependence or showing a certain degree of comorbidity, preliminary data indicate that single-agent therapy with carboplatin can confer the same benefit as combination chemotherapy, but with reduced toxicity. Single agent oral etoposide, however, seems to be inferior to combination treatment and should not be given routinely in the treatment of this cohort. Further evaluation of these topics is needed, and can be achieved by trials specifically designed for elderly patients or patients with reduced performance status.
Aged↗
Chemotherapy in elderly patients with advanced lung cancer. Part II: Treatment of non-small cell lung cancer (NSCLC).
Increasing interest in the treatment of elderly patients or patients with poor performance status (PS) with non-small cell lung cancer (NSCLC) has led to a number of subgroup analyses of clinical trials, and even more importantly, the conduction of trials specifically designed for this cohort. These studies allow some important conclusions. Data from retrospective studies and meta-analyses indicate that the use of platinum-based two-drug combinations in selected, fit elderly patients may produce response rates, survival, and toxicity comparable to those in younger patients. This excludes a per se inferior effectiveness of chemotherapy in the population of elderly patients with NSCLC. A number of more recently introduced agents with a favourable toxicity profile have significantly increased treatment options. Single- agent therapy with vinorelbine, when compared to best supportive care, has been shown to give a statistically significant survival benefit and improve quality of life. Conflicting data from phase II/III trials in elderly patients with NSCLC exist regarding a potential benefit of combination chemotherapy over single-agent treatment in the total cohort of elderly patients, including those with comorbidities or declining functional reserve. A review of the most important trials, assessing treatment options in elderly patients with lung cancer, either prospectively or retrospectively, is provided, and still unresolved issues are addressed.
Aged↗
Efficacy of cytotoxic agents used in the treatment of testicular germ cell tumours under normoxic and hypoxic conditions in vitro.
Platinum-based chemotherapy is the main treatment element to achieve cure for patients with metastatic germ cell tumours. Drug resistance in testicular germ cell tumours (TGCTs) is rare and the reasons are not fully understood. While recent investigations have indicated decreased efficacy of chemotherapy in several tumour types under hypoxic conditions, this aspect has not been investigated in TGCTs so far. Furthermore, for cisplatin - the most active drug in this disease - controversial effects of hypoxia on cytotoxic efficacy have been reported. The relative efficacy of cytotoxic agents for the treatment of TGCT patients was studied in three different cell lines derived from human embryonal carcinomas (EC) in an in vitro hypoxia model. NT2, 2102 EP, and NCCIT were tested for their sensitivity towards cisplatin, etoposide, bleomycin, 4-OOH-ifosfamide, carboplatin, paclitaxel, gemcitabine, oxaliplatin, irinotecan, and mitomycin C under normoxic and hypoxic conditions using the MTT assay. Inhibitory concentrations IC(50) of the tested agents under both conditions were compared. Selected results were confirmed by flow-cytometric assessment of the apoptotic index. In all cells, doubling times were prolonged in hypoxia (NT2<NCCIT<2102 EP). All drugs were less effective under hypoxic conditions, including mitomycin C (eg, 1.6-fold increase of IC(50) in hypoxia compared to normoxia for NT2) and cisplatin (eg, NT2: two-fold increase). The relative effect of hypoxia on the IC(50) depended mainly on the cell line, and to a lesser extent on the drug. The results indicate that the reduced cell proliferation in hypoxia might be an important factor, but not the only determinant of a reduced cytotoxicity. In view of the broad spectrum of drugs with different modes of action tested, the relative resistance cannot be mediated by substance-specific resistance mechanisms like hypoxia-induced upregulation of P-glycoprotein or increased DNA-repair capacity, since many unrelated drugs were affected to a comparable extent in their efficacy by hypoxia. This study also provides the rationale to test the hypothesis whether improving tumour oxygenation by raising haemoglobin concentrations, for example, with erythropoietin in patients with TGCTs receiving chemotherapy may improve the outcome.
Antineoplastic Agents↗
Protracted infusional 5-fluorouracil plus high-dose folinic acid combined with bolus mitomycin C in patients with gastrointestinal cancer: a phase I/II dose escalation study.
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%; CI(95%), 0-16) in colorectal and six (50%; CI(95%), 21-79%) in gastric cancer patients. In all, 17 (38%) achieved disease stabilisation, 15 colorectal (45%, CI(95%), 28-64%) and two gastric cancer patients (17%; CI(95%), 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.
Adenocarcinoma↗
Long-term results of first-line sequential high-dose etoposide, ifosfamide, and cisplatin chemotherapy plus autologous stem cell support for patients with advanced metastatic germ cell cancer: an extended phase I/II study of the German Testicular Cancer Study Group.
PURPOSE: Patients with disseminated germ cell cancer and poor prognosis (International Germ Cell Cancer Collaborative Group [IGCCCG] classification) achieve only a 45% to 50% long-term survival by standard chemotherapy. First-line high-dose chemotherapy might be able to improve the result. This analysis reports toxicity and long-term results of a large phase I/II study of sequential high-dose etoposide, ifosfamide, and cisplatin (VIP) in patients with advanced germ cell tumors. PATIENTS AND METHODS: Between July 1993 and November 1999, 221 patients with either Indiana "advanced disease" (n = 39) or IGCCCG "poor prognosis" criteria (n = 182) received one cycle of VIP followed by three to four sequential cycles of high-dose VIP chemotherapy plus stem cell support, every 3 weeks, at six consecutive dose levels. RESULTS: Dose limiting toxicity occurred at level 8 (100 mg/m2 cisplatinum, 1750 mg/m2 etoposide, 12 g/m2 ifosfamide) with grade 4 mucositis (three of eight patients), grade 3 CNS toxicity (one of eight patients), grade 4 renal toxicity (one of eight patients), and prolonged granulocytopenia (one of eight patients). After 4-year median follow-up, progression-free survival and disease-specific survival rates in the poor prognosis subgroup were 69% and 79% at 2 years and 68% and 73% at 5 years, with 76% for gonadal/retroperitoneal versus 67% for mediastinal primaries. Severe toxicity included treatment related death (4%), treatment-related acute myeloid leukemia (1%), long-term impared renal function (3%), chronic renal failure (1%), and persistent grade 2-3 neuropathy (5%). CONCLUSION: Repetitive cycles of high-dose VIP with peripheral stem cell support can be successfully applied in a multicenter setting. Dose level 6 with cisplatin 100 mg/m2, etoposide 1500 mg/m2, and ifosfamide 10 g/m2 is recommended for further investigation in randomized trials. An ongoing randomized trial within the European Organization for Research and Treatment of Cancer evaluates this protocol against four cycles of standard cisplatin, etoposide, and bleomycin.
Adolescent↗
Randomized phase III study of high-dose fluorouracil given as a weekly 24-hour infusion with or without leucovorin versus bolus fluorouracil plus leucovorin in advanced colorectal cancer: European organization of Research and Treatment of Cancer Gastrointestinal Group Study 40952.
PURPOSE: This trial was conducted to determine whether high-dose fluorouracil (FU) given as a weekly 24-hour infusion is more active than bolus FU + leucovorin (LV), and whether high-dose infusional FU can be modulated by LV. PATIENTS AND METHODS: A total of 497 patients with previously untreated metastatic colorectal cancer were randomly assigned to receive bolus FU 425 mg/m2 intravenously + LV 20 mg/m2 on days 1 to 5 and repeated on day 28 (FU + LV), or FU 2600 mg/m2 as a 24-hour infusion alone (FU24h) or in combination with 500 mg/m2 LV (FU24h + LV)-all given weekly x6 followed by a 2-week rest period. Survival was the major study end point. RESULTS: With a median follow-up of more than 3 years, survival did not differ among the treatment groups (median FU + LV, 11.1 months [95% CI, 10.2 to 15.0 months]; FU24h, 13.0 months [95% CI, 10.4 to 15.4 months]; FU24h + LV, 13.7 months [95% CI, 12.0 to 16.4 months]; P =.724). Progression-free survival (PFS) was significantly longer for FU24h + LV (median FU + LV, 4.0 months [95% CI, 3.4 to 4.9]; FU24h, 4.1 months [95% CI, 3.4 to 5.0]; FU24h + LV 5.6 months [95% CI, 4.4 to 6.7]; P =.029). The response rates in the subgroup of patients with measurable disease were 12%, 10%, and 17% for FU + LV, FU24h, and FU24h + LV, respectively (not significant). Occurrence of grade 3 and 4 diarrhea was higher in the FU24h + LV arm (22%) compared with the FU24h (6%) or FU + LV (9%) arms; however, stomatitis (11% in FU + LV v 3% in FU24h v 5% in FU24h + LV arms) and hematologic toxicity were higher in the bolus FU + LV arm. Global quality of life did not differ within the three arms. CONCLUSION: Neither FU24h + LV nor FU24h prolong survival, relative to bolus FU + LV. Leucovorin increases PFS if added to FU24h, but increases toxicity.
Adult↗
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.
Adult↗
[Is adrenalectomy an indispensable part of nephrectomy? Results of a multivariate statistical analysis].
Since in the absence of clinically overt metastatic disease tumorous lesions within the adrenal gland are found in only 2-10% of cases, the majority of renal cell cancer patients are overtreated by adrenalectomy as an integral part of nephrectomy. The medical records of 847 patients undergoing adrenalectomy in combination with nephrectomy irrespective of the local extent of the primary tumor or the clinical stage at first diagnosis were reviewed to determine the reliability of currently available imaging modalities regarding the prediction of adrenal gland metastases. Several patient and tumor characteristics correlated with the presence of intra-adrenal metastases, and their prognostic value was determined by a multivariate logistic regression model. Metastatic spread into the adrenal gland was observed in 27 of 847 (3%) patients. In only three of eight patients in whom the adrenal was identified as the only metastatic site, preoperative abdominal CT scans were interpreted as false negative. During multivariate statistical analysis, only the presence of distant metastases, vascular invasion within the primary tumor, and multifocal growth of renal cell cancer within the tumor-bearing kidney were identified to independently predict the likelihood for the presence of intra-adrenal metastases. None of the patient or tumor characteristics evaluated reliably predicted the likelihood for the presence of adrenal metastases in patients without evidence of disseminated metastatic spread. As we believe and as the current investigation demonstrates, routine adrenalectomy should not be recommended in cases of preoperatively normal radiological examinations.
Adrenal Gland Neoplasms↗
Analysis of salvage treatments for germ cell cancer patients who have relapsed after primary high-dose chemotherapy plus autologous stem cell support.
The aim of this study was to identify treatment strategies and therapeutic or clinical factors that predict for response to salvage therapy and survival in patients with metastatic 'Indiana advanced' or International Germ-Cell Cancer Collaborative Group (IGCCCG) poor prognosis' germ cell cancer (GCT) failing first-line sequential high-dose chemotherapy plus autologous stem cell support (HD-CT). A total of 58 'poor prognosis' patients who had relapsed after HD-CT were identified within two large prospective German first-line HD-CT trials (n=286) performed between March 1993 and March 2001. Salvage treatment consisted of the following: cisplatin-based conventional dose CTx+/-resection (19/58; 33%), non-cisplatin based CTx (16/58; 28%) or salvage HD-CT (14/58; 24%)+/-resection; resection (n=3) and/or radiation (n=5) only: 7 patients (12%); no specific therapy: 2 patients. 21 (38%) patients responded favourably (Complete Response (CR)/Partial Response (PR) marker-negative) to salvage therapy. The use of salvage HD-CT (2-year survival 48%; P=0.03, the complete resection of residual masses (2-year survival 42%; P=0.015) as well as a favourable response to salvage therapy (2-year survival: 31%, P=0.014) were the only variables on univariate analysis associated with an improved survival. The estimated 2-year overall survival rate is 32% (95% Confidence Interval CI: 29-45%). Approximately 30% of patients relapsing after first-line HD-CT will survive>2 years, particularly those patients who can be treated with a second HD-CT +and/or surgical resection. If feasible, complete surgical resection of residual tumours appears to be the most efficient treatment.
Adolescent↗