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C Bokemeyer

Publications and source records attributed to C Bokemeyer.

At least 55 records · Page 3Linked to original sources
PubMed2003

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↗
PubMed2003

Current aspects of high-dose chemotherapy in germ-cell tumors.

The optimal treatment in patients with 'poor prognosis' germ-cell tumors (GCT) according to the 'International Germ Cell Cancer Collaborative Group' (IGCCCG)--classification and in patients with refractory or relapsed disease after cisplatin-based chemotherapy remains controversial. It is well known that the majority of these patients will suffer systemic relapses after primary or salvage treatment and most of them will ultimately die of their disease. Therefore, the optimizing of the standard treatment is clearly desirable. The question of using conventional-dose or high-dose chemotherapy (HDCT) in this high-risk patients is under discussion. However, HDCT as primary treatment in 'poor prognosis' patients and as first- or subsequent salvage therapy in patients with relapsed or refractory GCT remains to be a relevant curative option. Prognostic factors have recently been recognized to aid in this decision.

Antineoplastic Agents↗
PubMed2003

[Impact of tumor size on long-term survival of patients with organ-confined renal cell cancer].

PURPOSE: As a result of the observation that the potential biological aggressiveness of even early stage renal cell cancer (RCC) strongly correlates with tumor size, the 5th edition of the TNM system (1997), which classifies all renal tumors up to a maximum diameter of 7 cm as T1, was modified in the current classification to distinguish T1a and T1b tumors based on a cut-off of 4 cm. Only a few larger investigations supporting this cut-off are available in the literature and these are based on univariate statistical analysis. To determine whether this cut-off best reflects the correlation between aggressive potential and tumor size and thus differentiates patients at low or high risk of progression, this investigation was performed using both univariate and multivariate statistical analysis. MATERIALS AND METHODS: Between 1981 and 2000, a total of 652 patients underwent tumor nephrectomy for renal cell carcinoma. Of these, the 243 patients with local RCC not extending beyond the renal capsule were subjected to univariate (log rank test) and multivariate (Cox regression model) statistical analysis. RESULTS: It became evident that, while during univariate analysis the prognostic calue of a cut-off size of 4 cm was confirmed, multivariate analysis identified the highest relative risk of cause-specific death (2.93) in those patients with tumors larger than 5 cm maximum diameter. CONCLUSIONS: The 5 cm cut-off thus appears to best determine the clinical prognosis for patients undergoing tumor nephrectomy for early stage renal call cancer. Taking this into consideration, the present study clearly demonstrates the reed for a multivariate statistical approach when the current modification of the TNM classification system is critically reevaluated.

Adult↗
PubMed2003

Towards an understanding of the biological basis of response to cisplatin-based chemotherapy in germ-cell tumors.

Chemotherapy is far more successful in young male patients with germ-cell tumors than in adults suffering from almost any other solid tumor. Various attempts have been made to understand the sensitivity of these tumors towards cisplatin-based chemotherapy; however, to date no explanation has been generally accepted. Recent data underline the need to seek further explanations, other than the previously postulated high intrinsic level of wild-type P53 protein, for the exquisite curability of germ-cell tumors. In this regard, the DNA repair pathways, in particular the DNA mismatch repair and nucleotide excision repair pathways, have received attention. This review summarizes the data currently available on the cellular basis for chemotherapy response in these tumors by systematically following cisplatin-presumably the most active drug in the treatment of this disease-on its course from entering the cell to the execution of apoptosis. The emerging picture points towards a multifactorial explanation for the unique chemosensitivity of germ-cell tumors, including a lack of export pumps, an inability to detoxify cisplatin and repair the respective DNA damage, and an intact apoptotic cascade not disturbed by anti-apoptotic stimuli. Even though no uniform pattern of relevant resistance factors has been identified in patients suffering from refractory disease, a significant number of these cases may be caused by defects in the DNA mismatch repair pathway.

Animals↗
PubMed2003

[Chemotherapy of advanced colorectal carcinoma: treatment options for elderly patients].

At present, approximately 70% of patients with colorectal cancer are older than 65 years at the time of diagnosis. This cancer population needs to be thoroughly assessed for the benefits of adjuvant or palliative chemotherapy. A comprehensive geriatric assessment may allow subdividing the population of elderly cancer patients into three groups thus helping to guide treatment decisions. It has been demonstrated that the use of 5-fluorouracil (5-FU) based adjuvant chemotherapy in elderly patients effectively reduces mortality and can be applied with acceptable toxicity. Systemic chemotherapy for patients with metastatic disease will have palliative effects and lead to prolongation of survival. While several data exist for the combination of 5-FU and folinic acid in elderly patients, data about combination chemotherapy with 5-FU and new drugs such as irinotecan or oxaliplatin is still limited. There appears to be an age-associated increase in drug-specific toxicity when these agents are used. However, for carefully selected elderly patients receiving adequate monitoring throughout therapy these new treatment approaches can be made available. Clinical studies also indicate that treatment effectiveness in selected elderly patients is comparable to that observed in the younger patient population. Future trials need to further redefine treatment strategies in elderly patients with colorectal cancer.

Aged↗
PubMed2002

Treatment-induced anaemia and its potential clinical impact in patients receiving sequential high dose chemotherapy for metastatic testicular cancer.

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.

Anemia↗
PubMed2002

Irinotecan in patients with relapsed or cisplatin-refractory germ cell cancer: a phase II study of the German Testicular Cancer Study Group.

Despite generally high cure rates in patients with metastatic germ cell cancer, patients with progressive disease on first-line cisplatin-based chemotherapy or with relapsed disease following high-dose salvage therapy exhibit a very poor prognosis. Irinotecan has shown antitumour activity in human testicular tumour xenografts in nude mice. We have performed a phase II study examining the single agent activity of irinotecan in patients with metastatic relapsed or cisplatin-refractory germ cell cancer. Refractory disease was defined as progression or relapse within 4 weeks after cisplatin-based chemotherapy or relapse after salvage high-dose chemotherapy with autologous stem cell support. Irinotecan was administered at a dose of 300 (-350) mg m(-2) every 3 weeks. Response was evaluated every 4 weeks. Fifteen patients have been enrolled. Median age was 35 (19-53) years. Primary tumour localisation was gonadal/mediastinal in 12/3 patients. Patients had been pretreated with a median of six (4-12) cisplatin-containing cycles and 13 out of 15 patients had previously failed high-dose chemotherapy with blood stem cell support. Median number of irinotecan applications was two (1-3). Fourteen patients are assessable for response and all for toxicity. In one patient, no adequate response evaluation was performed. Toxicity was generally acceptable and consisted mainly of haematological side effects with common toxicity criteria 3 degrees anaemia (two patients), common toxicity criteria 3 degrees leukocytopenia (one patient) and common toxicity criteria 3 degrees thrombocytopenia (three patients). Common toxicity criteria 3/4 degrees non-haematological toxicity occurred in five patients (33%): 1 x diarrhoea, 2 x alopecia, 1 x fever and in one patient worsening of pre-existing peripheral polyneuropathy from 1 degrees to 4 degrees. No response was observed to irinotecan therapy. Currently, 13 patients have died of the disease and two patients are alive with the disease. The patients included in our study exhibit similar prognostic characteristics as patients treated in previous trials evaluating new drugs in this setting. Irinotecan at a dose of 300-350 mg m(-2) every 3 weeks appears to have no antitumour activity in patients with cisplatin-refractory germ cell cancer and, thus, further investigation in this disease is not justified.

Adult↗
PubMed2002

Absence of c-KIT and members of the epidermal growth factor receptor family in refractory germ cell cancer.

BACKGROUND: Germ cell tumors (GCTs) in adolescent and young males are very sensitive to cisplatin-based chemotherapy. However, 10-20% of the patients cannot be cured by currently available therapeutic options. Once a tumor does not respond to cisplatin, current therapeutic modalities offer only a chance for short palliation. Recently, new treatment options that interfere with various receptor tyrosine kinases, including c-KIT and members of the epidermal growth factor receptor (EGFR) family, have been used successfully in chemotherapy-resistant tumors overexpressing c-KIT, ERB-B2, or EGFR. METHODS: We studied the presence of c-KIT and the four members of the EGFR family by immunohistochemistry, as well as by ERB-B2 gene amplification using fluorescent in situ hybridization, in a series of 22 patients with cisplatin-resistant GCTs in search of new treatment targets. The results in these refractory tumors were compared with those of 12 patients with chemosensitive GCTs diagnosed in an advanced metastatic stage. RESULTS: The data obtained in both groups did not differ in any of the investigated biologic markers. c-KIT was detected in the one case of pure seminoma studied and in the seminomatous components of combined tumors. The presence of EGFR was restricted to trophoblastic giant cells and the syncytiotrophoblastic elements of four nonseminomas including one pure choriocarcinoma and to a secondary non-germ cell malignancy, which had developed most likely from a mature teratoma. ERB-B2 was moderately positive in the secondary non-germ cell malignancy, in one mature teratoma component of a mixed nonseminoma, and together with EGFR in the syncytiotrophoblastic cells of a pure choriocarcinoma. Of all samples investigated, this latter case was the only one showing an amplification of the ERB-B2 gene in the syncytiotrophoblasts. ERB-B3 and ERB-B4 were detected rarely. CONCLUSION: The majority of refractory GCTs do not qualify for treatment with new biologic agents targeting the receptor tyrosine kinases EGFR, ERB-B2, or c-KIT. The lack of differences between the tumors of refractory and the responsive patients indicates that overexpression of any of these receptor tyrosine kinases does not contribute to a resistant phenotype in GCTs.

Adolescent↗
PubMed2002

Surgical bladder preserving strategies in the treatment of muscle-invasive bladder cancer.

Single modality bladder-sparing therapy for muscle-invasive bladder cancer, including transurethral resection (TUR), partial cystectomy, systemic chemotherapy or radiotherapy, have been demonstrated to result in insufficient local control of the primary tumour, as well as decreased long-term survival in the patients when compared to radical cystectomy. Therefore, multimodality treatment protocols that aim at bladder preservation and involve all of the aforementioned approaches have been established. Arguments for combining systemic chemotherapy with radiation are to sensitise tumour tissue to radiotherapy and to eradicate occult metastases that have already developed in as many as 50% of patients at the time of first diagnosis. It has been shown that the clinical outcome observed with this approach approximates that after radical cystectomy. Additionally, a substantial number of patients survive with an intact bladder. However, bladder-sparing approaches are costly, and require close co-operation between different clinical specialists as well as careful follow-up. The good long-term results that are observed after cystectomy and the creation of an orthotopic neobladder make the substantial advantage of a bladder preservation strategy questionable when the patient's quality of life is addressed. Additionally, bladder-sparing therapy-related side effects might result in an increased morbidity and mortality in those patients who need to undergo surgery due to recurrent or progressive disease. Multimodality bladder-sparing treatment is a therapeutic option that can be offered to the patient at centres that have a dedicated multidisciplinary team at their disposal. However, radical cystectomy remains the standard of care for muscle-invasive bladder cancer.

Humans↗
PubMed2002

Activity of oxaliplatin in patients with relapsed or cisplatin-refractory germ cell cancer: a study of the German Testicular Cancer Study Group.

PURPOSE: To investigate the efficacy and toxicity of oxaliplatin, a diaminocyclohaxane platinum derivative with incomplete cross-resistance to cisplatin in patients with relapsed or cisplatin-refractory germ cell cancer. PATIENTS AND METHODS: Thirty-two patients with nonseminomatous cisplatin-refractory germ cell cancer or relapsed disease after high-dose chemotherapy (HDCT) plus autologous stem-cell support were treated with single-agent oxaliplatin 60 mg/m(2) on days 1, 8, and 15 repeated every 4 weeks (group 1; n = 16) or oxaliplatin 130 mg/m(2) given on days 1 and 15 of a 4-week cycle (group 2; n = 16). Patients were pretreated with a median of seven (range, three to 13) cisplatin-containing treatment cycles; 78% had received carboplatin/etoposide-based HDCT before oxaliplatin therapy. Twenty-seven patients (84%) were considered refractory (n = 20; 63%) or absolutely refractory (n = 7; 22%) to cisplatin therapy. RESULTS: Overall, four patients achieved a partial remission (13%; 95% confidence interval, 1% to 24%). Two additional patients achieved disease stabilization. All responses were observed in cisplatin-refractory patients, including three who had not responded to previous HDCT. Patients received a median two cycles of oxaliplatin with a median cumulative dose of 350 mg/m(2). Hematologic toxicity was generally mild, with five patients developing grade 3/4 thrombocytopenia. Nonhematologic side effects consisted mainly of nausea/vomiting. One patient developed grade 3 neurotoxicity. CONCLUSION: Considering the particularly unfavorable prognostic characteristics of this patient population compared with patients from previous trials for new drugs in germ cell cancer, eg, paclitaxel and gemcitabine, a 13% overall response rate and a 19% response rate in the group treated with oxaliplatin 130 mg/m(2) seems to be of interest. Oxaliplatin may be a palliative treatment option for this patient population, and evaluation in combination regimens is warranted.

Adult↗
PubMed2002

Early prediction of treatment response to high-dose salvage chemotherapy in patients with relapsed germ cell cancer using [(18)F]FDG PET.

To assess the ability of [(18)F]fluorodeoxyglucose positron emission tomography for the early prediction of response in patients with relapsed metastatic germ cell tumours undergoing salvage high-dose chemotherapy. The role of positron emission tomography was compared with established means of tumour response assessment such as CT scans/MRI and serum tumour marker changes. In addition, positron emission tomography was compared with a current prognostic score which differentiates three prognostic groups with failure-free survival rates ranging from 5-50%. [(18)F]fluorodeoxyglucose uptake of metastases from germ cell tumours as well as CT scans and serum tumour marker were acquired after 2-3 cycles of induction chemotherapy but before the start of high-dose chemotherapy and CT scans/serum tumour marker were compared with the baseline examinations in 23 patients with relapsed germ cell tumours. To evaluate the validity of early response prediction by positron emission tomography, radiological monitoring and serum tumour marker decline, histopathologic response after resection of residual masses and/or the clinical course over 6 months after the end of treatment (relapse vs freedom of progression) were used. Overall, 10 patients (43%) achieved a marker-negative partial remission, three (13%) a marker-positive partial remission, five (22%) a disease stabilization and five (22%) progressed during treatment. Nine patients (39%) remained progression-free over 6 months following treatment, whereas 14 (61%) progressed. The outcome of high-dose chemotherapy was correctly predicted by positron emission tomography/CT scan/serum tumour marker in 91/59/48%. Eight patients with a favourably predicted outcome by CT scans plus serum tumour marker but a positive positron emission tomography prior to high-dose chemotherapy, failed treatment. This results in the following sensitivities/specificities for the prediction of failure of high-dose chemotherapy: positron emission tomography 100/78%; radiological monitoring 43/78%; serum tumour marker 15/100%. The positive and negative predictive values of positron emission tomography were 88 and 100%, respectively. As compared with the prognostic score, positron emission tomography was correctly positive in all patients of the three risk groups who failed treatment. In addition, a negative positron emission tomography correctly predicted a favourable outcome in the good and intermediate group. [(18)F]fluorodeoxyglucose positron emission tomography imaging can be used to assess response to chemotherapy in patients with relapsed germ cell tumours early in the course of treatment and may help to identify patients most likely to achieve a favourable response to subsequent high-dose chemotherapy. In patients with response to induction chemotherapy according to CT scans or serum tumour marker evaluation, positron emission tomography seems to add information to detect patients with an overall unfavourable outcome. It may also be a valuable addition to the prognostic model particularly in the good and intermediate group for further selection of patients who will profit from high-dose chemotherapy.

Adult↗
PubMed2002

The need for routine adrenalectomy during surgical treatment for renal cell cancer: the Hannover experience.

OBJECTIVES: To further clarify the need for routine adrenalectomy during the surgical treatment of renal cell cancer, as in the absence of clinically overt metastatic disease, tumorous lesions within the adrenal gland are found in only 2-10% of patients, with most being over-treated by adrenalectomy. PATIENTS AND METHODS: The medical records of 819 patients undergoing adrenalectomy combined with nephrectomy, irrespective of the local extension of the primary tumour or the clinical stage at first diagnosis, were reviewed to determine the reliability of currently available imaging methods in predicting adrenal gland metastases. Several patient and tumour characteristics were correlated with the presence of intra-adrenal metastases, and their possible independent prognostic value was determined by a multivariate logistic regression model. RESULTS: There was metastatic spread into the adrenal gland in 27 of 819 (3.3%) patients. In only three of eight patients in whom the adrenal was identified as the only metastatic site were preoperative abdominal computed tomography scans interpreted as false-negative. On multivariate statistical analysis only the presence of distant metastases, vascular invasion within the primary tumour and multifocal growth of renal cell cancer within the tumour-bearing kidney were identified as independent predictors of the presence of intra-adrenal metastases. CONCLUSIONS: None of the patient or tumour characteristics evaluated reliably predicted the likelihood of adrenal metastases in patients with no evidence of disseminated metastatic spread. However, previously published data indicate that the frequency of metachronous metastases within the contralateral kidney (1.8-3.8%) is significantly higher than the risk of a preoperatively undetected isolated intra-adrenal metastatic lesion when currently available imaging modalities are applied. Therefore, routine adrenalectomy should not be recommended if the preoperative radiological examinations are normal.

Adrenal Gland Neoplasms↗
PubMed2002

[Therapy of elderly patients with colorectal carcinoma].

Treating elderly patients with colorectal cancer is a challenging task for which many aspects have to be taken into account. Almost 70% of patients with colorectal cancer are 65 years or older and the number of elderly patients is expected to increase. As elderly patients frequently exhibit adverse physical or socio-economic conditions, a thorough geriatric assessment of the patient's suitability for therapy is essential before making a decision. The first line treatment for colorectal cancer is surgery. Complete resection of the tumor should also be attempted in elderly patients, as there are little differences in cancer--specific survival in selected elderly patients compared to younger patients. Surgery with palliative intention can be attempted for symptom control or to prevent later local complications caused by the primary tumor. At present, adjuvant 5-FU based chemotherapy (in colon cancer) and adjuvant radio-chemotherapy (in rectal cancer) in the elderly is recommended for locally advanced or node positive tumor after tumor resection, since the benefit seems to be comparable to that achieved in younger patients. There is also enough data to support the use of 5-FU based chemotherapy in elderly patients in the palliative setting. New drugs have recently been added to the armentarium for the treatment of metastatic colorectal cancer. However, there is as yet not sufficient data to guide the use of these new drugs (such as oxaliplatin or irinotecan) in elderly patients. However, first clinical studies seem to indicate a comparable efficacy and toxicity in elderly patients to that observed in younger patients. Further clinical trials of chemotherapy in elderly patients with colorectal cancer are necessary to gain information about treatment recommendations. It is the aim of this manuscript to summarize the current knowledge about the management of colorectal cancer in elderly patients.

Aged↗
PubMed2002

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.

Administration, Oral↗
PubMed2002

Prognostic variables for response and outcome in patients with extragonadal germ-cell tumors.

BACKGROUND: This investigation evaluates prognostic variables in patients with seminomatous and non-seminomatous extragonadal germ-cell tumors (EGCT) in order to identify relevant factors for long-term outcome following cisplatin-based chemotherapy. PATIENTS AND METHODS: Patients from six countries treated at 11 centers in Europe and the USA from 1975 to 1996 were evaluated retrospectively. Uni- and multivariate analyses of prognostic variables for survival and for response to chemotherapy were performed. RESULTS: Data were available for 635 EGCT patients, 104 with seminomatous and 524 with non-seminomatous EGCT (n = 7 not specified). For non-seminomatous EGCT the following independent adverse factors were identified: presence of either liver, lung or central nervous system metastases, primary mediastinal tumor or elevation of pretreatment beta-human gonadotropin; for extragonadal seminoma (only univariate) adverse factors were: presence of liver metastases, two or greater metastatic sites or International Germ Cell Cancer Collaborative Group (IGCCCG) grouping (intermediate versus good). Integration of these variables produced the following prognostic risk groupings: 'excellent prognosis', all seminomatous EGCT (89% 5-year survival rate); 'intermediate low', 'intermediate high' and 'poor', all non-seminomatous EGCT with a 69, 55 and 17% 5-year survival rate, respectively. The decreased survival among the different groups was due to a lower rate of favorable objective remissions and a higher rate of relapses. Classification and regression tree (CART) modeling confirmed histology and location of primary tumor as the major prognosticators. For the subgroup of patients with mediastinal non-seminoma, the 2-year survival rate ranged from 34 to 84%. Multivariate testing for the probability to respond to chemotherapy revealed non-seminomatous histology, primary mediastinal tumor site, and the presence of liver, lung or CNS metastases as independent adverse factors. CONCLUSIONS: In EGCT, prognostic variables for the outcome and for the response to chemotherapy could be identified, which in part differ from gonadal GCT. The proposed model might help to better understand the specific prognosis of EGCT and to tailor risk-adapted treatment strategies. In addition, CART analysis demonstrated the heterogenous prognosis of patients with mediastinal non-seminoma.

Abdominal Neoplasms↗