Biomedical subjects

J T Hartmann

Publications and source records attributed to J T Hartmann.

At least 37 records · Page 2Linked to original sources

PubMed2004

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↗

PubMed2004

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↗

PubMed2004

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↗

PubMed2004

Hypersensitivity pneumonitis associated with the use of trofosfamide.

Trofosfamide (Ixoten; Baxter Oncology, Germany) is an alkylating agent that, as with other oxazaphosphorine derivatives, has to be activated by hepatic cytochrome P450 oxidases. The bioavailability is nearly 100% after oral application, and the main metabolites are 4-hydroxytrofosfamide, and 4-hydroxyifosfamide. The main side-chain metabolites ifosfamide and cyclophosphamide can be further activated by oxidation and formation of their respective phosphoramide mustards. Oral continuous low-dose therapy has been the most widely used schedule. The toxicity profile consists mainly of dose-dependent hematotoxicity and, rarely, hemorrhagic cystitis. Nausea and vomiting are infrequently seen. Higher grades of nephrotoxicity or neurotoxicity--side-effects that typically limit the use of ifosfamide-have not been reported with low-dose continuous trofosfamide treatment. We report herein a case of a 83-year-old female patient with a disseminated malignant peripheral nerve sheath tumor treated with trofosfamide developing pulmonal toxicity. To our knowledge, this is the first reported case of exogenous allergic alveolitis after exposure to this drug.

Administration, Oral↗

PubMed2003

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↗

PubMed2003

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↗

PubMed2003

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↗

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↗

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

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↗

PubMed2002

Phase II study of weekly paclitaxel plus 24-h continuous infusion 5-fluorouracil, folinic acid and 3-weekly cisplatin for the treatment of patients with advanced gastric cancer.

The aim of this study was to evaluate the toxicity and efficacy of combination chemotherapy with weekly 24-h continuous infusion of 5-fluorouracil (5-FU)/folinic acid, weekly paclitaxel and 3-weekly cisplatin in patients with unresectable, locally advanced or metastatic gastric adenocarcinoma. Between November 1999 and November 2001, 29 chemotherapy-naive patients (13 male and 16 female) with a median age of 56 years (range 22-72) were consecutively enrolled at three centers. 5-FU 2 g/m2 was given weekly over 24 h i.v. preceded by folinic acid 500 mg/m2 as a 2-h infusion. Paclitaxel 80 mg/m2 was administered as a 1-h infusion weekly and cisplatin 50 mg/m2 as 1-h infusion on days 8 and 29. Six weeks of therapy (days 1, 8, 15, 22, 29 and 36) followed by 1 week of rest was considered one cycle. A median of 3 cycles (range 1-5) was administered to 29 patients with a total of 73 cycles applied. All patients were assessable for toxicity and survival, 28 patients were assessable for response (one patient received less than one complete cycle and could not be evaluated for response). Four patients (14%) obtained a complete response and 10 patients (34%) a partial response (overall response rate 48%, 95% CI 29-68%). Seven patients (24%) had stable disease. Seven patients (24%) had progressive disease during or within 4 weeks after treatment. The median progression-free and overall survival times were 8 months (range 1-23) and 11 months (range 1-23), respectively. Overall toxicity was acceptable. Hematological toxicity was favorable with only one patient (3%) experiencing WHO grade 3/4 leukocytopenia and one patient (3%) WHO grade 3/4 anemia. Non-hematologic WHO grade 3/4 toxicities included alopecia in 19 (66%), nausea/vomiting in six (21%), diarrhea in six (21%), neurotoxicity grade 3 in three (10%) and infection in three (10%) patients. A total of 42 applications (10%) (range 0-5) had to be postponed and dose reductions of at least one drug was necessary in 37% of applications. In three patients (10%) treatment was stopped because of toxicity. All patients were treated on an outpatient basis. Thus, the combination of weekly paclitaxel, cisplatin and continuously infused 5-FU/folinic acid appears to be a highly active regimen for the treatment of patients with advanced gastric cancer. Compared with our previous experience with the same combination of drugs but using paclitaxel at 175 mg/m2 given every 3 weeks, the protocol with weekly application of paclitaxel 80 mg/m2 shows a reduced incidence of hematologic toxicity, particularly leukopenia. Other organ toxicities apart from a slightly higher incidence of peripheral neuropathy were comparable between the two treatment protocols. Efficacy with a response rate of 50% was well preserved by this weekly regimen.

Adenocarcinoma↗

PubMed2001

Incidence of metachronous testicular cancer in patients with extragonadal germ cell tumors.

BACKGROUND: The frequency of subsequent testicular cancer (referred to as metachronous testicular cancer) in men who have had previous testicular cancer is relatively high. The rate of metachronous testicular cancer in men with extragonadal germ cell tumors (EGCTs), however, is largely unknown. We conducted a retrospective study of EGCT patients to determine the incidence, cumulative risk, and specific risk factors for metachronous testicular cancers. METHODS: A standardized questionnaire about patient characteristics, the extent of EGCT disease, any second malignancies, and treatments received was completed for 635 patients with EGCTs identified from the medical records of 11 cancer centers in Europe and the United States from 1975 through 1996. Comparisons with age group-specific data from the Saarland, Germany, population-based cancer registry were used to calculate the standardized incidence ratio (SIR). The Kaplan-Meier method was used to analyze survival data and cumulative risk. All statistical tests were two-sided. RESULTS: Sixteen EGCT patients (4.1%) developed metachronous testicular cancers, with a median time between diagnoses of 60 months (range, 14-102 months). The risk of developing metachronous testicular cancers was statistically significantly increased in patients with EGCTs (observed = 16; expected = 0.26; SIR = 62; 95% confidence interval [CI] = 36 to 99) and in subsets of EGCT patients with mediastinal location (SIR = 31; 95% CI = 8 to 59), retroperitoneal location (SIR = 100; 95% CI = 54 to 172), and nonseminomatous histology (SIR = 75; 95% CI = 43 to 123). The cumulative risk of developing a metachronous testicular cancer 10 years after a diagnosis of EGCT was 10.3% (95% CI = 4.9% to 15.6%) and was higher among patients with nonseminomatous EGCTs (14.3%; 95% CI = 6.7% to 21.9%) and retroperitoneal EGCTs (14.2%; 95% CI = 5.6% to 22.8%) than among patients with seminomatous EGCTs (1.4%; 95% CI = 0.0% to 4.2%) and mediastinal EGCTs (6.2%; 95% CI = 0.1% to 12.2%). CONCLUSIONS: Patients with EGCTs, particularly those with retroperitoneal or nonseminomatous tumors, but also those with primary mediastinal EGCTs, are at an increased risk of metachronous testicular cancer.

Adolescent↗

PubMed2001

Viable malignant cells after primary chemotherapy for disseminated nonseminomatous germ cell tumors: prognostic factors and role of postsurgery chemotherapy--results from an international study group.

PURPOSE: To assess the value of postsurgery chemotherapy in patients with disseminated nonseminomatous germ-cell tumors (NSGCTs) and viable residual disease after first-line cisplatin-based chemotherapy. PATIENTS AND METHODS: The outcome of 238 patients was reviewed. Tumor markers had normalized in all patients before resection. A multivariate analysis of survival was performed on 146 patients. RESULTS: The 5-year progression-free survival (PFS) rate was 64% and the 5-year overall survival (OS) rate was 73%. Three factors were independently associated with both PFS and OS: complete resection (P <.001), < 10% of viable malignant cells (P =.001), and a good International Germ Cell Consensus Classification (IGCCC) group (P =.01). Patients were assigned to one of three risk groups: those with no risk factors (favorable group), those with one risk factor (intermediate group), and those with two or three risk factors (poor-risk group). The 5-year OS rate was 100%, 83%, and 51%, respectively (P <.001). The 5-year PFS rate was 69% (95% confidence interval [CI], 62% to 76%) and 52% (95% CI, 40% to 64%) in postoperative chemotherapy recipients and nonrecipients, respectively (P <.001). No significant difference was detected in 5-year OS rates. After adjustment on the three prognostic factors, postoperative chemotherapy was associated with a significantly better PFS (P <.001) but not with better OS. Patients in the favorable risk group had a 100% 5-year OS, with or without postoperative chemotherapy. Postoperative chemotherapy appeared beneficial in both PFS (P <.001) and OS (P =.02) in the intermediate-risk group but was not statistically beneficial in the poor-risk group. CONCLUSION: A complete resection may be more critical than recourse to postoperative chemotherapy in the setting of postchemotherapy viable malignant NSGCT. Immediate postoperative chemotherapy or surveillance alone with chemotherapy at relapse may be reasonable options depending on the completeness of resection, IGCCC group, and percent of viable cells. Validation is necessary.

Adult↗

PubMed2001

Extragonadal seminoma: an international multicenter analysis of prognostic factors and long term treatment outcome.

BACKGROUND: The objectives of this study were to evaluate the long term outcome of patients with extragonadal seminomatous germ cell tumors (GCT) so that prognostic variables for disease recurrence and patient survival could be identified and to access the efficacy of different treatment modalities. METHODS: Six hundred thirty-five patients with extragonadal GCT who were treated consecutively at 11 centers in the United States and Europe during the cisplatin-based chemotherapy era between 1975 and 1996 were evaluated retrospectively. RESULTS: Fifty-two patients with primary retroperitoneal GCT (50%) and 51 patients with primary mediastinal GCT (49%) of pure seminomatous histology were identified (n = 1 patient with a primary cervical lymph node) representing 16.4% of 635 patients with extragonadal GCT who were included in the data base. The median age was 37 years (range, 18-70 years). Treatment consisted of platin-based chemotherapy in 77 patients (74%), radiotherapy in 9 patients (9%), and combined modality in 18 patients (17%). Ninety-two percent of patients (95% confidence interval, 87-97%) achieved a favorable response to primary therapy. After a median follow-up of 61 months (range, 1-211 months), 18 patients (17%) have had recurrent disease: 14% of those who received chemotherapy and 67% of those who received radiation therapy. The 5-year progression free survival rate favored the chemotherapy group, with 87% compared with 33% for irradiated patients (P = 0.006), whereas the overall survival rates were equal (90% vs. 67%; P = 0.13). No differences in overall survival or progression free survival were observed among patients with primary retroperitoneal and mediastinal seminoma. Prognostic factors that were identified to influence survival negatively were liver metastases (P = 0.01) and two or more metastatic sites (P = 0.04). CONCLUSIONS: In patients with extragonadal seminoma, a survival rate of > 90% at 5 years is achieved with adequate cisplatin-based chemotherapy. Compared with patients with nonseminomatous extragonadal GCT, no difference in long term survival exists between patients with primary retroperitoneal or mediastinal seminoma location. Primary radiotherapy seems to be associated with a significantly higher rate of disease recurrence, although most patients will be salvaged by subsequent chemotherapy.

Adolescent↗

PubMed2001

Second-line chemotherapy in patients with relapsed extragonadal nonseminomatous germ cell tumors: results of an international multicenter analysis.

PURPOSE: Relapsed extragonadal germ cell tumors patients (EGGCT) are treated with identical salvage chemotherapy regimens, as are patients with metastatic testicular cancer. This investigation evaluates the results of second-line chemotherapy in nonseminomatous EGGCT and tries to identify prognostic factors for survival. PATIENTS AND METHODS: We conducted a retrospective review of 142 patients treated at eleven European and American centers between 1975 and 1996. All had received cisplatin-containing regimens as induction treatment. RESULTS: Twenty-seven of 142 patients (19%) were long-term disease-free, 11% with primary mediastinal and 30% of patients with primary retroperitoneal disease. Median follow-up since start of salvage treatment was 11 months (range, 1 to 157) for all patients and 45 months (range, 6 to 157) for surviving patients. Forty-eight patients (34%) received high dose chemotherapy with autologous bone marrow transplant at relapse, and 10 of these patients (21%) are continuously disease-free. Primary mediastinal location (P =.003), sensitivity to cisplatin (P =.003), elevated beta-HCG at relapse (P: =.04), and normal LDH at diagnosis (P =.01) were shown to be significant negative prognostic factors for overall survival in univariate; mediastinal location [relative risk ratios (HR) = 1.9; 95% confidence intervals (CI), 1.2 to 3.0] and sensitivity to cisplatin [HR = 2.4; 95% CI, 1.1 to 5.2] were significant negative prognostic factors in multivariate analysis. CONCLUSION: Although current salvage strategies will cure between 20% and 50% of recurrent metastatic testicular cancer, relapsed nonseminomatous EGGCT patients appear to have an inferior survival rate, in particular in case of primary mediastinal location. Mediastinal primary tumor and inadequate response to cisplatin-based induction chemotherapy have been identified as independent negative prognostic factors, both associated with an approximately two-fold higher risk for failure of salvage treatment.

Adolescent↗

PubMed2001

A randomized trial of amifostine in patients with high-dose VIC chemotherapy plus autologous blood stem cell transplantation.

This pilot study evaluates the degree of side effects during high-dose chemotherapy (HD-VIC) plus autologous bone marrow transplant (HDCT) and its possible prevention by the cytoprotective thiol-derivate amifostine. Additionally, the in-patient medical costs of both treatment arms were compared. 40 patients with solid tumours were randomized to receive HD-VIC chemotherapy with or without amifostine (910 mg/m(2)at day 1-3) given as a short infusion prior to carboplatin and ifosfamide. Patients were stratified according to pretreatment. HDCT consisted of an 18 h infusion of carboplatin (500 mg/m(2/)d over 18 h), ifosfamide (4 g/m(2)/d over 4 h) and etoposide (500 mg/m(2)/d) all given for 3 consecutive days. All patients received prophylactic application of G-CSF (5 microg kg(-1)subcutaneously) to ameliorate neutropenia after treatment. Patients were monitored for nephrotoxicity, gastrointestinal side effects, haematopoietic recovery, as well as frequency of fever and infections. The median fall of the glomerular filtration rate (GFR) was 10% from baseline in the amifostine group (105 to 95 ml min(-1)) and 37% in the control patient group (107 to 67 ml min(-1)) (P< 0.01). Amifostine-treated patients revealed a less pronounced increase in albumin and low molecular weight protein urinary excretion. Stomatitis grade III/IV occurred in 25% without versus 0% of patients with amifostine (P = 0.01). Acute nausea/vomiting was frequently observed immediately during or after the application of amifostine despite intensive antiemetic prophylaxis consisting of 5-HT3-receptor antagonists/dexamethasone/trifluorpromazine. However, delayed emesis occurred more often in the control patients. Engraftment of neutrophil (> 500 microl(-1))and thrombocytes (> 25 000 microl(-1))were observed at days 9 versus 10 and 10 versus 12, respectively, both slightly in favour of the amifostine arm. In addition, a lower number of days with fever and a shortened duration of hospital stay were observed in the amifostine arm. The reduction of acute toxicity observed in the amifostine arm resulted in 30% savings in costs for supportive care (Euro 4396 versus Euro 3153 per patient). Taking into account the drug costs of amifostine, calculation of in-patient treatment costs from the start of chemotherapy to discharge revealed additional costs of Euro 540 per patient in the amifostine arm. This randomized pilot study indicates that both organ and haematotoxicity of HD-VIC chemotherapy can be ameliorated by the use of amifostine. Additionally, a nearly complete preservation of GFR was observed in amifostine-treated patients which may be advantageous if repetitive cycles of HDCT are planned. Larger randomized trials evaluating amifostine cytoprotection during high-dose chemotherapy are warranted.

Adult↗

PubMed2001

Salvage treatment with paclitaxel, ifosfamide, and cisplatin plus high-dose carboplatin, etoposide, and thiotepa followed by autologous stem-cell rescue in patients with relapsed or refractory germ cell cancer.

PURPOSE: To study feasibility and efficacy of a new salvage regimen in patients with relapsed and/or refractory germ cell tumors. PATIENTS AND METHODS: Between May 1995 and February 1997, 80 patients were entered onto a phase II study. Conventional-dose salvage treatment with three cycles of paclitaxel 175 mg/m(2), ifosfamide 5 x 1.2 g/m(2), and cisplatin 5 x 20 mg/m(2) (TIP) was followed by one cycle of high-dose chemotherapy (HDCT) with carboplatin 500 mg/m(2) x 3, etoposide 600 mg/m(2) x 4, and thiotepa 150 to 250 mg/m(2) x 3 (CET). In 23 patients, one additional cycle of paclitaxel 175 mg/m(2) and ifosfamide 5 g/m(2) (TI) was given immediately before TIP to improve stem-cell mobilization. RESULTS: Fifty-five (69%) of 80 patients responded to TIP, 24 (30%) of 80 patients had stable disease (n = 5) or tumor progression (n = 19), and one patient died. Only 62 (78%) of 80 patients received subsequent HDCT. Among those, 41 (66%) of 62 patients responded and 20 (32%) of 62 patients had stable disease (n = 3) or tumor progression (n = 17). One patient died after HDCT from multiorgan failure. Survival probabilities at 3 years were 30% for overall and 25% for event-free survival. Peripheral neurotoxicity with sensorimotor impairment grade 2 through 4 in 29%, paresthesias grade 2 through 4 in 24%, and skin toxicity grade 2 through 3 in 15% of patients were the most relevant side effects. CONCLUSION: Treatment with TIP followed by high-dose CET is feasible and can induce long-term remissions in 25% of patients with relapsed or refractory germ cell tumors. Peripheral nervous toxicity in approximately one third of patients is a disadvantage of this salvage strategy.

Antineoplastic Combined Chemotherapy Protocols↗