PubMed Health⌕ Search

Biomedical subjects

J T Hartmann

Publications and source records attributed to J T Hartmann.

At least 73 records · Page 4Linked to original sources
PubMed1999

Diagnosis and treatment of patients with testicular germ cell cancer.

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

Antineoplastic Agents↗
PubMed1999

UFT/calcium folinate plus weekly paclitaxel for solid tumors.

Since cancer is incurable in many patients, palliation of symptoms and quality-of-life issues are important aspects of therapy. Uracil and tegafur (UFT) plus calcium folinate are the components of the oral agent known as Orzel, which offers activity comparable to intravenously administered 5-fluorouracil (5-FU) combined with calcium folinate. Paclitaxel (Taxol), administered intravenously on a weekly schedule, offers high dose intensity and high response rates with limited hematologic toxicity. It is the aim of this phase I study to define the dose-limiting toxicity, possible antitumor activity, and appropriate phase II study dose for the combination of UFT plus calcium folinate administered orally for 4 weeks plus weekly doses of paclitaxel. The daily dose will be fixed at UFT 300 mg/m2 plus calcium folinate 90 mg, both divided into three doses per day; paclitaxel will be escalated in each cohort of patients in 10-mg/m2 steps, starting with 50 mg/m2 weekly. This protocol will take the success of protracted 5-FU infusion--here achieved orally with UFT plus calcium folinate--in combination with paclitaxel one step further by using paclitaxel in a dose-dense, less toxic weekly schedule. It may be anticipated that an active outpatient therapy for a variety of solid tumors will result.

Adolescent↗
PubMed1998

[Prognostic relevance of vena cava thrombosis in renal cell carcinoma].

The independent prognostic value of neoplastic extension of renal cell cancer (RCC) into the vena cava inferior has been the subject of several investigations reported to date. However, the use of vena cava thrombosis as an independent prognosticator of a patient's long-term survival is still debated. We have therefore correlated the clinical course of 53 patients with RCC and vena cava thrombosis with a control group consisting of 47 patients with renal cell tumors without vena cava thrombosis (follow-up: 1-154 months). The median long-term survival of patients with and without vena cava thrombosis was 32 and 35 months, respectively. Neither the propagation of the tumor into the vena cava (P = 0.391) nor the cranial extension of the thrombosis (P = 0.158)--even in case of propagation into the right atrium--could be identified as parameters of any prognostic value during univariate or multivariate statistical analysis.

Adult↗
PubMed1998

Recent strategies for the use of paclitaxel in the treatment of urological malignancies.

Paclitaxel, a natural anticancer drug, has gained widespread acceptance as an active broad-spectrum antitumor agent, including its use in urological malignancies, particularly urothelial tract cancer and testicular cancer. The mechanism of action, based on the premature stabilization of the microtubule assembly with disruption of the cytoskeletal framework, is completely different from those of DNA-damaging agents, e.g., cisplatin and ifosfamide. As a single agent, paclitaxel is one of the most active drugs in metastatic bladder cancer, with an overall response rate of 40-50% being obtained in previously untreated patients. These promising single-agent results have prompted the use of combination regimens including, in particular, cisplatin and paclitaxel. A high degree of activity for the cisplatin-paclitaxel combination as reflected by responses in 50-80% of patients, including a substantial number of complete responses (> 30%), has been identified. The role of other agents such as vinorelbine, methotrexate, 5-fluorouracil, or ifosfamide as additions to this two-drug combination currently remains open. The combination of paclitaxel plus ifosfamide or vinorelbine in the absence of a platinum derivative has yielded rather disappointing results. Of particular interest may be the combination of paclitaxel and carboplatin. Both drugs can be given to patients with impaired renal function. Overall response rates of 45-60% have been reported in phase II studies. The so-called platelet-sparing effect of paclitaxel given in combination with carboplatin has resulted in a surprisingly low frequency of myelotoxicity, particularly thrombocytopenia. The combination of paclitaxel with carboplatin is being compared in an ongoing trial against the current standard MVAC regimen (methotrexate/vinblastine/Adriamycin/cisplatin) in patients with metastatic disease. Furthermore, the activity of paclitaxel-based combinations is currently being explored in the neoadjuvant setting in phase II studies, and the potential for the combination with the other new promising agent--gemcitabine--will be evaluated in a phase I setting. In prostate cancer, estramustine phosphate is widely used as palliative treatment for patients with hormone-refractory disease. In vitro synergistic activity has been observed between estramustine and paclitaxel in prostate-cancer cell lines, although paclitaxel has not demonstrated single-agent activity in patients with hormone-refractory prostate cancer. In clinical trials the combination of the two agents was associated with increased gastrointestinal toxicity. The addition of etoposide as a third drug has yielded prostate-specific antigen (PSA)-response rates of > 50%, but data on quality of life and survival time have not been reported for these combinations. A true clinical role for paclitaxel in prostate cancer has therefore not been established. Paclitaxel has finally demonstrated single-agent activity in relapsed and/or cisplatin-refractory testicular cancer in recent phase II trials, indicating different mechanisms of resistance to cisplatin and paclitaxel. These results have formed the rationale for the introduction of paclitaxel as part of combination chemotherapy regimens in patients with relapsed but chemosensitive testicular cancer. Preliminary results demonstrate that paclitaxel can be safely included into these conventional-dose combination regimens. When it is used prior to high-dose chemotherapy, sufficient numbers of peripheral blood stem cells (PBSCs) for high-dose therapy can be collected. The final role of paclitaxel in risk-adapted chemotherapeutic strategies in testicular cancer is not defined, but it appears that paclitaxel-based combinations can achieve a substantial response rate in patients with relapsed disease.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Risk of secondary myeloid leukemia and myelodysplastic syndrome following standard-dose chemotherapy or high-dose chemotherapy with stem cell support in patients with potentially curable malignancies.

Secondary acute myeloid leukemia (s-AML) and secondary myelodysplastic syndrome (s-MDS) probably represent the worst possible long-term complications of cancer therapy in patients originally cured of their primary malignancy. The frequency and type of s-AML and s-MDS are reviewed for patients treated with standard and/or high-dose chemotherapy for Hodgkin's disease, non-Hodgkin's lymphoma (NHL), and breast or testicular cancer. Patients treated for Hodgkin's disease, have a 20- to 40-fold increased risk of developing s-AML, this risk increasing with the number of mechlorethamine-containing cycles given as well as following splenectomy and in patients more than 40-50 years of age. Generally, patients with NHL, breast or testicular cancer experience a lower, 2- to 15-fold, risk of developing s-AML. Epipodophyllotoxins appear to be the most important factor for s-AML in patients treated for testicular cancer. Doses of 2g/m2 or more are associated with an increased risk of s-AML and, with these high doses, a cumulative incidence of 2% 3% at 5 years is observed. Adjuvant cyclophosphomide, methobrexate, 5-Fu therapy in breast cancer patients does not appear to increase risk significantly as compared to the general population. The extent of the leukemogenic potential of anthracyclines remains to be defined. NHL patients receiving mechlorethamine, prednimustine or long-term maintenance therapy are also at an increased risk of s-AML. A considerably increased risk of developing AML, with a cumulative incidence of approximately 9% at 5 years, has been observed following allogenic bone marrow transplantation (ABMT) or peripheral stem cell transplantation (PBSCT) in patients with NHL. It is likely that the increased risk of s-AML/s-MDS following high-dose chemotherapy with ABMT or PBSCT is related to prior treatment rather than to high-dose chemotherapy itself. However, this issue remains to be conclusively addressed. s-AML or s-MDS rarely develops after allogenic bone marrow transplantation. s-AML and s-MDS increasingly represent a problem in modern cancer therapy because of better treatment strategies, which result in improved cure rates. Patients who receive chemotherapy must be informed about the potential risk of developing s-AML or s-MDS. Future studies should include a follow-up long enough to record the occurrence of all s-AML/s-MDS and all potential influencing factors reliably. These data would enable risk factors to be defined and risk/benefit analyses to be carried out, allowing the correct assessment of current and future therapy strategies.

Acute Disease↗
PubMed1998

Phase I pharmacological study of intra-arterially infused fotemustine for colorectal liver metastases.

Fotemustine was investigated in 17 patients with progressive hepatic metastases from colorectal carcinoma to define the maximally tolerated dose for a daily hepatic intra-arterial infusion (HAI) schedule. Haematotoxicity was delayed, dose-dependent and related to pretreatment, with thrombo- and leucocytopenia being dose-limiting. Local side-effects at the liver were mild. Infection (WHO grade III) occurred in 1 patient due to neutropenia. Other side-effects, particularly renal, pulmonal, neurological or cardiac toxicity, mucositis and diarrhoea, hair loss or allergic reactions did not occur. Pharmacokinetic analysis indicated a short plasma half-life (t1/2 = 25.8 +/- 11.5 min) and a high body clearance (CL = 2193 +/- 870 ml/min) with large inter- and intra-individual variations. Of 15 evaluable patients, one complete and three partial responses were observed (ORR = 27%; CI95% [4.5-49.5%]). All tumour remissions appeared at higher dose levels in previously untreated patients. Considering the absence of mucosal side-effects, such as mucositis/diarrhoea and of hepatic toxicity, this agent was well tolerated. The recommended intra-arterial dose for consecutive phase II trials is 125 mg/m2/day1-3.

Adolescent↗
PubMed1998

Analysis of risk factors for cisplatin-induced ototoxicity in patients with testicular cancer.

This study evaluates the degree and relevance of persisting ototoxicity after cisplatin-based standard-dose chemotherapy for testicular cancer, with emphasis on identification of potential factors for an increased risk of this late sequel. Hearing thresholds of 86 patients with a median age of 31 years (range 21-53 years) and a median follow-up time of 58 months (range 15-159 months) were assessed by conventional pure-tone audiometry. Interviews were conducted evaluating the patients' history with special regard to audiological risk factors, as well as circumstances of ototoxic symptoms. Details concerning treatment and patient variables were extracted retrospectively from the patients' charts. An additional screening programme assessed current body functions, blood parameters and other late toxicities. Symptomatic ototoxicity persisted in 20% of patients (59% tinnitus, 18% hearing loss, 23% both), while 10% had experienced completely reversible ototoxic symptoms for a duration of 1-18 months after treatment. Symptoms were bilateral in 81% of patients. Hearing thresholds were compatible with cisplatin-induced hearing loss in 42% of audiograms performed. Subjective (history) and objective (audiogram) findings were not always consistent. The following statistically significant risk factors for ototoxicity were established: high cumulative dose of cisplatin (P < 0.0001); history of noise exposure (P = 0.006). Additionally, high doses of vincristine (P = 0.001) seemed to result in reversible ototoxic symptoms. No other independent risk factors were identified. In conclusion, persisting ototoxicity represents a clinical sequel for approximately 20% of testicular cancer patients treated at standard dose but may affect more than 50% of patients receiving cumulative doses of cisplatin > 400 mg m(-2). Previous noise exposure may also result in a threefold increased risk for cisplatin ototoxicity. Future studies should use these risk factors as important stratification criteria for trials aiming at the evaluation and prevention of cisplatin-induced ototoxicity.

Adult↗
PubMed1998

Phase II study of continuous 120 h infusion of mitomycin C as salvage chemotherapy in patients with progressive or rapidly recurrent colorectal cancer.

We evaluated the therapeutic activity and safety of continuously infused mitomycin C in patients with metastatic colorectal cancer who had recurred (less than 3 months) or progressed following first- or second-line 5-fluorouracil-based chemotherapy. Treatment consisted of mitomycin C 20 mg/m2 i.v. given over 120 h (5 days) followed by a 3 week rest period. Fifty-two consecutively enrolled patients were assessable for toxicity and 49 for response evaluation (three patients evaluable but not measurable), completing at least one full course of chemotherapy. Previous chemotherapy regimens consisted of bolus 5-fluorouracil/folinic acid (5-FU/FA) (Machover) n=26 (50%) or continuous (24 h) 5-FU+/-FA+/-interferon n=26 (50%). Forty-two percent of patients had received one previous chemotherapy regimen and 58% more than one. One partial remission (2%) lasting 7 months and 11 disease stabilizations (23%) with a median duration of 3.2 months (range 1-8) were achieved in 49 patients. Median survival time since start of mitomycin C was 4.7 months (1.2-28.1) resulting in a 6 month survival rate of 36%. The progression-free interval was 10 weeks (range 4-36). Delayed and cumulative thrombo- and leukocytopenia (WHO grade III/IV) were observed in 19 and 6%, and anemia in 2% of patients. WHO grade I/IV mucositis, diarrhea and fever/infection occurred each in 6% of patients. Treatment delays and dose reductions were necessary in 11 (21%) and 21 (40%) patients, respectively. In three cases treatment was stopped due to cumulative thrombocytopenia (6%). Continuous infusion of single-agent mitomycin C displays modest activity in heavily pretreated 5-FU refractory colorectal cancer patients combined with a low toxicity level.

Adult↗
PubMed1998

Secondary leukemia following high cumulative doses of etoposide in patients treated for advanced germ cell tumors.

PURPOSE: High cumulative epipodophyllotoxin dosages are reported to be associated with an elevated risk for secondary acute myeloid leukemia (s-AML). This study examined the risk of s-AML following cumulative etoposide doses greater than 2 g/m2 in patients with metastatic germ cell tumors (GCT). PATIENTS AND METHODS: The incidence of s-AML was retrospectively assessed in patients treated within clinical trials between January 1986 and February 1996 at four university centers. All patients received high-dose chemotherapy (HDCT) plus autologous stem-cell support for metastatic GCT, including high cumulative etoposide doses (> 2 g/m2). Minimum patient follow-up was 12 months. Standardized morbidity ratio (SMR) was calculated to estimate the risk associated with high cumulative etoposide doses, as compared with the general population. RESULTS: A total of 302 patients with a median age of 29 years (range, 15 to 55) received a median cumulative etoposide dose of 5 g/m2 (range, 2.4 to 14 g/m2). Four cases of s-AML were observed, which resulted in a cumulative incidence of 1.3% (95% confidence interval [CI], 0.38% to 3.59%) at 52 months of median follow-up (range, 12 to 198). Two cases of secondary myelodysplasia (s-MDS) developed in patients with primary mediastinal GCT. Based on the observed four cases of AML, which are most likely etoposide-related, the risk for developing s-AML (SMR, 160 [95% CI, 43.7 to 411.2]) is significantly increased in comparison to the age-matched general population. CONCLUSION: Due to the low incidence of AML in the general population, the significantly elevated risk for developing s-AML affects only 1.3% of all patients who receive etoposide doses greater than 2 g/m2. HDCT, including etoposide doses greater than 2 g/m2, is associated with an acceptably low incidence of s-AML in patients with advanced GCT.

Acute Disease↗
PubMed1998

The use of dose-intensified chemotherapy in the treatment of metastatic nonseminomatous testicular germ cell tumors. German Testicular Cancer Study Group.

With the use of a cisplatin-based chemotherapy, metastatic testicular cancer has become a model for a highly curable malignant disease. Current data show that 70% to 80% of patients with this disease will achieve long-term survival following cisplatin/etoposide/bleomycin therapy. The role of high-dose chemotherapy with autologous stem cell support is being investigated in metastatic germ cell cancer in attempts to improve outcome for patients whose disease relapses after standard-dose chemotherapy and for those who present initially with advanced metastatic disease. Prognostic categories for patients receiving high-dose salvage chemotherapy have recently been developed: cisplatin-refractory disease, beta-human chorionic gonadotropin values greater than 1,000 U/L, and primary mediastinal germ cell tumors are factors characterizing patients who will derive less benefit from high-dose chemotherapy than those with chemosensitive disease at relapse. While standard-dose salvage chemotherapy achieves only a 20% long-term survival rate, high-dose salvage chemotherapy may yield a cure rate of approximately 40%. A randomized study comparing high-dose therapy with conventional-dose therapy (IT94 coordinated by the European Group for Blood and Marrow Transplantation) in patients with relapsed disease is ongoing to substantiate this observation. The use of dose-intensive therapy as first-line treatment is currently being studied by several institutions. High-dose therapy may be better tolerated when used first line compared with its use in the salvage situation, and may also achieve a rapid initial cell kill before cytostatic drug resistance develops. The German Testicular Cancer Study Group has developed a sequential high-dose combination regimen of cisplatin/etoposide/ifosfamide given with granulocyte colony-stimulating factor and peripheral blood stem cell support for four cycles every 3 weeks. This ongoing study, started in 1990, had accrued 218 patients with advanced testicular germ cell tumors as of June 1997. Of 141 evaluable patients receiving dose levels 1 through 5, 82 (58%) have achieved complete remission with no evidence of disease and 32 (23%) have achieved partial remission with marker normalization. The early death rate was 8%. Overall and event-free survival rates at 2 years are 78% and 73%, respectively, with a projected 5-year overall survival rate of 74%. Despite favorable preliminary results, this approach cannot be considered standard treatment. Currently, high-dose chemotherapy with peripheral blood stem cell transplantation should be administered to patients with testicular cancer only within controlled clinical trials to allow long-term cure rates and treatment-related late side effects to be evaluated.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

A phase I/II study of sequential, dose-escalated, high dose ifosfamide plus doxorubicin with peripheral blood stem cell support for the treatment of patients with advanced soft tissue sarcomas.

BACKGROUND: This Phase I/II study investigates increasingly high doses of ifosfamide combined with full dose doxorubicin chemotherapy supported with peripheral blood stem cells (PBSC) and granulocyte-colony stimulating factor (G-CSF) in patients with metastatic soft tissue sarcoma (STS). METHODS: Patients with histologically proven metastatic or advanced adult STS without prior treatment received doxorubicin, 75 mg/m2, on Day 1 followed by 4-day continuous infusion of ifosfamide at 5 consecutive dose levels starting with 8 g/m2 and escalating to 16 g/m2 in increments of 2 g/m2. Three patients per dose level and a maximum of 5 treatment cycles per level at 3-week intervals were planned. Each cycle was followed by G-CSF and retransfusion of PBSC. PBSC separation was performed prior to chemotherapy by steady state mobilization with G-CSF. RESULTS: Eighteen patients (median age, 45 years, range, 25-57 years) were included, with 4, 3, 4, 4, and 3 patients assigned to Levels 1-5, respectively. Metastatic sites included the lungs in 12 patients (67%), lymph nodes in 8 patients (44%), and the liver in 5 patients (28%). Nine patients (50%) achieved objective responses with 4 complete responses (22%) and 5 partial responses (28%). Lung metastases and a histology of synovial sarcoma or malignant fibrous histiocytoma were favorable features for response to therapy. The median survival for all patients was 13+ months (range, 3-19+ months). Hematotoxicity was manageable and treatment could be administered at a median interval of 24 days. One case of World Health Organization Grade 3 neurotoxicity occurred. Nephrotoxicity was dose-limiting, with 1 patient in Level 4 (WHO Grade 2) and 2 patients in Level 5 (WHO Grade 3). CONCLUSIONS: Multiple cycles of dose-intensive therapy with doxorubicin and high dose ifosfamide can be administered safely with PBSC support. Nephrotoxicity is dose-limiting for ifosfamide at total doses of 16 g/m2. Multiple cycles of high dose chemotherapy at short treatment intervals using ifosfamide at a dose of 14 g/m2 should be investigated further in a neoadjuvant setting in patients with STS.

Adult↗
PubMed1997

[Current aspects of adjuvant and palliative chemotherapy in colorectal carcinoma].

With an annual incidence rate of 30 to 40 per 100,000 colorectal carcinoma is the second most frequent malignancy in Germany. Despite the poor outcome of patients suffering from this disease important advances have been made in the standardisation and improvement of palliative and adjuvant treatment in patients with colorectal cancer. For the systemic chemotherapy 5-fluorouracil (5-FU) remains the most important cytotoxic agent and biomodulation of the therapeutic activity of 5-FU with methotrexate or particularly folinic acid has been clinically established, yielding response rates in 20 to 35% of patients. Current investigations of systemic treatment are aiming into three directions: 1. investigation of high-dose continuous (24-hours) 5-FU application (with or without modulation by folinic acid); 2. evaluation of new, effective cytotoxic agents, among which the camphotecin derivative CPT-11 (irenotecan) and the specific thymidilate synthase inhibitor Tomudex appear to be the most promising drugs as single agents and/or in combination with 5-FU; 3. use of orally available fluoropyrimidine derivatives with high bioavailability which may substantially improve the quality of life in palliative therapy. The postoperative adjuvant treatment of patients with Dukes C colorectal cancer is established clinical practice and the combination of 5-FU and levamisol given for one year will result in an improved overall survival of about 15% at five years compared to surgery alone. Although this regimen remains the current standard treatment, alternatives for the adjuvant treatment may be the use of 5-FU and folinic acid given for only half a year post surgery, locoregional perfusion of the liver with 5-FU alone via the portal vene by 7-day continuous application or the use of 17-1A monoclonal antibody immunotherapy after curative resection. Further improvement may be achieved by the combination of immunotherapy and chemotherapy which is currently tested in clinical studies. Future recommendations for the adjuvant treatment of colorectal cancer will not only be based on therapeutic efficacy but will also have to take costs of treatment into account. Better definition of high-risk patient groups for adjuvant treatment is needed.

Antineoplastic Agents↗
PubMed1997

Comparison of histological results from the resection of residual masses at different sites after chemotherapy for metastatic non-seminomatous germ cell tumours.

Cisplatin-based combination chemotherapy is considered standard treatment for patients with metastatic testicular cancer. However, despite the normalisation of serum tumour markers, 25-50% of patients will demonstrate residual neoplastic masses on radiological examination after completion of chemotherapy. The management of patients presenting with multiple residual masses at different localisations remains particularly difficult. This report summarises the histological findings and the clinical outcome of 27 patients with metastatic non-seminomatous germ cell tumours who underwent multiple resections for residual masses at different localisations after first-line cisplatin-based chemotherapy at Hannover University Medical School between 1980 and 1995. Fifty-six resections were performed (27 retroperitoneal interventions, 21 thoracotomies, 4 resections of hepatic lesions, 3 neck dissections, 1 craniotomy). No surgery-related mortality was observed. 8 patients (30%) showed dissimilar histological findings at sequential or one-stage resections. 5 of these demonstrated less favourable pathological features (mature teratoma or undifferentiated tumour) at the second operation, while only necrosis (n = 3) or teratoma (n = 2) had been found following the first operation. Tumour necrosis was documented more frequently at thoracotomy (n = 15/21) compared to retroperitoneal lymph node excision (n = 17/27). By univariate analysis, completeness of surgery (R0 resection) and the histological finding of necrosis or differentiated teratoma were associated with improved relapse-free and overall survival. After a median follow-up period of 33 months (range 1-167), 19 of 26 (73%) evaluable patients are alive; 18 of 27 (67%) patients have continuous no evidence of disease (1 patient with recurrent disease was lost to follow-up). Since the histological findings in postchemotherapy residuals may vary between different anatomical sites and no prediction seems possible, patients are best managed by excision of all present tumour masses if technically feasible. Necrosis identified at thoractomy should not lead to omission of retroperitoneal lymph node resection since there was, in accordance to other authors, a trend that the retroperitoneum harbours unfavourable histological findings more frequently.

Adolescent↗
PubMed1997

Postchemotherapy resections of residual masses from metastatic non-seminomatous testicular germ cell tumors.

PURPOSE: To analyse the frequencies of histological findings, predictive factors for the presence of undifferentiated tumor and variables influencing the survival of patients with non-seminomatous germ cell tumors who underwent secondary resection of residual masses after cisplatin-based combination chemotherapy. PATIENTS AND METHODS: 134 patients with a median age of 26 years (15-47) undergoing at least one surgical intervention at Hannover University Medical School were included. One hundred nine patients had received first-line chemotherapy and 25 underwent surgery after second-line chemotherapy. RESULTS: After first-line chemotherapy the distribution of histological findings was 52% necrosis, 27% differentiated teratoma and 21% undifferentiated tumor for 82 patients with marker negative PR (PRm-). Incompletely resected mass and failure to achieved complete tumor marker normalisation were significantly associated with the finding of undifferentiated tumor. Five-year progression-free survival rates according to histological findings were 78%, 67% and 66% for necrosis, differentiated teratoma and undifferentiated tumor. Patients with undifferentiated tumor in the resected specimen routinely received postoperative additional chemotherapy. Factors associated with a worse overall survival were progressive disease within three months, persistent AFP elevation prior to surgery, prechemotherapy elevated LDH levels or mediastinal lymph node involvement at primary diagnosis. In 8 of 27 patients (30%) undergoing multiple resections at different sites a dissimilar histology was found. In the 25 patients operated after salvage chemotherapy undifferentiated tumor was found in 80%. A five-year survival of 44% compared to 80% after first-line chemotherapy was achieved. CONCLUSIONS: Resection of residual tumors after first-line chemotherapy remains essential in the treatment of metastatic testicular cancer. Undifferentiated tumor may still be found in 20% of patients despite achieving PRm-after first-line chemotherapy. Necrosis is found in only 50% of marker normalized patients after first-line and approximately 30% after second-line chemotherapy. Future studies have to prove whether the combination of clinical prognostic factors and the use of PET-scanning will allow to spare subsets of patients from secondary resection.

Adolescent↗
PubMed1997

A phase II trial of paclitaxel and weekly 24 h infusion of 5-fluorouracil/folinic acid in patients with advanced gastric cancer.

A phase II trial was performed to evaluate the efficacy and toxicity of the combination of paclitaxel and 5-fluorouracil (5-FU)/folinic acid in patients with advanced gastric carcinoma. Twenty-two patients (six female and 16 male) with advanced or metastatic disease were enrolled. None of them had received prior chemotherapy. Paclitaxel was administrated as a 3 h infusion of 175 mg/m2 at days 1 and 22, 5-FU 2000 mg/m2 i.v. over 24 h and folinic acid 500 mg/m2 i.v. 2 h prior to 5-FU weekly from days 1 to 36. Seven patients (32%) had partial remissions including the lungs, skin, lymph nodes and locally advanced primary tumor. The median overall survival was 11 months (range 1-17+) and the median progression-free interval was 8 months (range 1-13+). Neutropenia (WHO grade III/IV) occurred in 14% of patients. Other main toxicities were alopecia in 45%, fever/infection in 9%, and nausea/vomiting and diarrhea in 5%. In conclusion, the combination of paclitaxel and continuously infused 5-FU/folinic acid appears to be an active regimen for advanced gastric carcinoma with a remission rate comparable to ELF or FAMtx. The moderate toxicity allows treatment on an outpatient basis.

Adult↗
PubMed1997

Treatment of brain metastases in patients with testicular cancer.

PURPOSE: Despite improved cure rates for patients with metastatic testicular cancer with cisplatin-based combination chemotherapy, patients who develop brain metastases are generally considered to possess a poor prognosis. This report summarizes the long-term results in 44 patients with brain metastases from testicular cancer treated between 1978 and 1995 at Hannover University Medical School. PATIENTS AND METHODS: Histologically, 42 patients (95%) had a nonseminomatous germ cell cancer and two patients (5%) a seminoma. Thirty-nine patients (89%) had lung metastases and 37 (84%) fulfilled the criteria for advanced disease according to the Indiana University classification even without considering the brain metastases. Eighteen patients (41%) presented with brain metastases at primary diagnosis (group 1), four (9%) developed brain metastases at relapse after a previous favorable response to combination chemotherapy (group 2), and 22 (50%) developed brain metastases during or directly after cisplatin-based chemotherapy. Chemotherapy consisted of cisplatin-based combination treatment and radiotherapy was given as whole-brain irradiation of 30 to 40 Gy and in single cases combined with a boost of 10 Gy to single lesions. RESULTS: Overall, 10 patients achieved long-term survival (23%; 95% confidence interval [CI], 10.1% to 35.4%). The prognosis was significantly better for patients in groups 1 and 2, with six of 18 (33%) and three of four (75%) patients alive, compared with only one of 22 (5%) in group 3 (P < .01). Patients treated with either chemotherapy or radiotherapy alone did not achieve long-term survival, while nine of 28 (32%) who received treatment with both modalities with or without surgery achieved sustained long-term survival. During univariate analysis, patients with the diagnosis of brain metastases at first presentation (P < .01), patients with a single brain lesion (P < .02), and patients who received combined chemotherapy and radiotherapy (P < .03) had a significantly improved outcome. CONCLUSIONS: Long-term survival can be achieved in approximately 25% of patients with brain metastases from testicular cancer by combined treatment with brain irradiation and aggressive cisplatin-based chemotherapy. Patients who develop brain metastases during systemic treatment should receive only palliative radiation therapy, since sustained survival will not be reached.

Adolescent↗