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C Bokemeyer

Publications and source records attributed to C Bokemeyer.

At least 145 records · Page 8Linked to original sources
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

Modulation of 5-fluorouracil with methotrexate and low-dose N-(phosphonacetyl)-L-aspartate in patients with advanced colorectal cancer. Results of a phase II study.

Methotrexate (MTX) and N-phosphonacetyl-L-aspartate acid (PALA) have been shown to modulate the cytotoxic effects of 5-fluorouracil (5-FU). A phase II study was initiated to evaluate the feasibility, toxicity and efficacy of PALA/MTX and 5-FU in patients with metastatic colorectal cancer. 26 patients received PALA 250 mg/m2 as an intravenous 15-min infusion plus MTX 200 mg/m2 as a 30-min intravenous (i.v.) infusion on day 1 and 5-FU 600 mg/m2 as i.v. push on day 2. Cycles were repeated every 14 days and the 5-FU dose was escalated in the individual patient in steps of 100 mg/m2 for the third, fifth and seventh cycle in the absence of toxicity. 7 patients had received prior 5-FU-based chemotherapy while 19 patients were chemotherapy naive. Objective responses occurred in 23% of patients (1 CR, 5 PR of which 2 were pretreated), no change in 13 patients (50%) and tumour progression (6 patients) or toxic death (one patient) in 27%. Responses lasted for a median of 7 months (range 6-9), the median time to progression was 4 months and median survival 13 months. Toxicity was mainly gastrointestinal with diarrhoea and mucositis, and severe or life threatening in only 3 patients. In 3 patients an increase in serum glucose levels occurred while being treated with PALA/MTX and 5-FU. 2 patients with insulin-dependent diabetes had a 33% increase in insulin requirement and 1 patient with dietary-controlled diabetes died due to a ketoacidotic coma. PALA/MTX/5-FU in this dose and schedule is active in patients with colorectal cancer. Hyperglycaemia may be a potential side-effect of PALA-containing regimens especially in patients with diabetes. Careful monitoring of serum glucose levels in these patients is indicated.

Adult↗
PubMed1997

Comparative cytotoxicity of oxaliplatin and cisplatin in non-seminomatous germ cell cancer cell lines.

Approximately 70-80% of patients with metastatic testicular cancer will become disease free with cisplatin-based chemotherapy and most of these patients will be long-term survivors. Despite these impressive results, the two limitations of cisplatin are its severe and potentially long-term side-effects, and the emergence of drug resistance which prevents a small proportion of these patients from achieving long-term remission. Oxaliplatin has an improved toxicity profile compared to cisplatin and contains the diaminocyclohexane (DACH) substituent known to be correlated with a lack of cross-resistance with cisplatin. A phase II study has shown interesting activity when used in combination with cisplatin in cisplatin-refractory testicular cancer patients. Here we report the results of the first in vitro study investigating whether oxaliplatin as a single agent exhibits cross-resistance to cisplatin in a panel of non-seminomatous germ cell tumor (NSGCT) cell lines using short and long-term drug exposures in a five-day sulfhodamine B in vitro cytotoxicity assay. Oxaliplatin cytotoxicity was significantly superior to cisplatin in cell lines with both acquired (H12DDP) and intrinsic (1777NRp Cl-A) intermediate level resistance to cisplatin. Following 24 h or 96 h drug exposure the fold resistance in H12DDP and 1777NRp Cl-A was 1.7-2.2 with oxaliplatin compared to 3.9-6.1 with cisplatin. The cytotoxic activity of oxaliplatin was not significantly different from that of cisplatin in cisplatin-sensitive cell lines or in cell lines with a high level (10-20 fold) of cisplatin resistance. The results of this study suggest that further preclinical studies in NSGCT are of interest, particularly in combination with cisplatin, ifosfamide and etoposide. Furthermore, the in vitro results support the use of an oxaliplatin administration schedule giving prolonged drug exposure, such as the flat or circadian rhythm-modulated schedule already under investigation for oxaliplatin.

Adult↗
PubMed1997

Pre-clinical activity of taxol in non-seminomatous germ cell tumor cell lines and nude mouse xenografts.

Taxol (Paclitaxel) is a novel anti-cancer drug which has shown excellent clinical activity in a variety of solid tumors, particularly in metastatic breast and ovarian cancer. 70-80% of patients with metastatic non-seminomatous germ cell tumor (NSGCT) attain disease-free status with standard cisplatin-based combination chemotherapy but the emergence of drug resistance still prevents a small proportion of these patients from achieving long-term remission. Here we report the results of pre-clinical studies investigating whether taxol exhibits cross-resistance to cisplatin or ifosfamide in human NSGCT cell lines and in a cisplatin refractory xenograft model of human NSGCT. Following 96-h drug exposure in a 5-day sulphohodamine B (SRB) in vitro assay, taxol demonstrated potent cytotoxicity in cell lines which were cisplatin sensitive (577 LM, H32, H12.1; mean IC50s 1.5-3.0 nM) or those with acquired or intrinsic cisplatin resistance (H12DDP, H23.1; mean IC50s 2.5 nM). Compared to the drug-sensitive cell line, H12.1, the IC50 values of taxol were increased in cell line 1777NRp Cl-A with intermediate level resistance to cisplatin and ifosfamide (4.7 nM; p > 0.05) and significantly elevated in cell line 1411HP, with a high level of cisplatin resistance (6.9 nM; p < 0.01). The latter 2 cell lines may represent models corresponding to patients relapsing after high-dose platinum-based chemotherapy who seem to be resistant to taxol therapy. The IC50s of taxol in H32 and H12DDP were approximately 100-fold lower following drug exposure times exceeding 24 hours compared with short exposure times (1-6 h). Dose-dependent anti-tumor activity was observed with taxol in a cisplatin-refractory xenograft model of NSGCT (H23.1), with significant anti-tumor activity observed at a dose of 15 mg/kg/d injected intravenously on days 1 through 5. The results of this study are in accordance with the most recent clinical data which showed that taxol is a useful drug in relapsed or cisplatin-refractory testicular germ cell cancer, with significant anti-tumor activity being observed in 25% of patients, but poor activity in patients previously treated with high-dose therapy. Further pre-clinical research, especially using models such as 1411HP and 1777NRp Cl-A, on the combinations of taxol with other regimens are required to enable successful treatment of the most drug-resistant relapsed germ cell tumors.

Animals↗
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

Chemotherapy for germ cell tumors relapsing after high-dose chemotherapy and stem cell support: a retrospective multicenter study of the Austrian Study Group on Urologic Oncology.

BACKGROUND: In most patients with advanced refractory germ cell tumors undergoing high-dose chemotherapy with stem cell support (HDCT) the disease progresses after HDCT. This study was designed to shed light on the unestablished role of post-HDCT chemotherapy. PATIENTS AND METHODS: In a retrospective multicenter study data of 47 evaluable patients from nine centers subjected to post-HDCT chemotherapy for progression of their germ cell tumors were collected in a questionnaire survey and analyzed for treatment response and survival. RESULTS: Of 191 patients pretreated by HDCT, 48 (25%) were subjected to post-HDCT chemotherapy for disease progression. Remission was achieved in 17 (36%) and marker-negative remission in eight (17%). The median survival time was 26 weeks, 65 weeks for responders and 13 weeks for non-responders. Only one of 47 evaluable patients achieved sustained complete remission. Remissions significantly correlated with the post-HDCT interval, the use of ifosfamide and the combination regimens of cisplatin + etoposide i.v. or ifosfamide and of paclitaxel + ifosfamide or cisplatin. On univariate analysis a longer post-HDCT interval, the use of cisplatin, paclitaxel and ifosfamide and the combined use of paclitaxel + ifosfamide and/or cisplatin significantly improved the chances of survival. On multivariate analysis only treatment with paclitaxel and ifosfamide retained independent prognostic significance for survival. CONCLUSIONS: One third of the patients considered to be candidates for further chemotherapy once progressive after HDCT went into remission with a gain in survival time. Sustained remissions may occur, but are rarely seen. Paclitaxel and ifosfamide appear to be the most effective drugs in these heavily pretreated patients.

Adult↗
PubMed1997

Prognostic relevance of intracaval neoplastic extension for patients with renal cell cancer.

OBJECTIVE: To assess the diagnosis of vena caval thrombosis (VCT) in patients with renal cell carcinoma (RCC) as an independent indicator of prognostic importance and when combined with additional tumour characteristics in a controlled multivariate analysis. PATIENTS AND METHODS: The clinical course of 53 patients (41 men and 12 women, mean age 60 years, range 35-79) with RCC and VCT was compared with that of a control group of 47 patients (37 men and 10 women, mean age 57 years, range 32-76) with RCC but no neoplastic extension into the vena cava. RESULTS: With a follow-up of 1-154 months and a mean long-term survival of 32 and 35 months, respectively, for patients with and without VCT, neither the propagation of the tumour into the vena cava (P = 0.391) nor the cranial extension of the thrombosis (P = 0.158) were identified as having any prognostic value during univariate or multivariate statistical analysis. The presence of regional lymph node (P < 0.001) or distant metastases (P = 0.009) was an independent prognostic variable for patients with RCC, with a significant decrease in long-term survival (13 and 14 months for patients with lymph node and distant metastases, respectively). CONCLUSION: A radical surgical approach is essential as standard therapy for the treatment of patients with RCC and neoplastic extension into the vena cava. Because they have a significantly decreased life expectancy, asymptomatic patients with lymph node or distant metastases should be treated conservatively.

Adult↗
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↗
PubMed1997

Paclitaxel and weekly 24-hour infusion of 5-fluorouracil/folinic acid in advanced gastric cancer.

The current phase II study evaluates the safety and efficacy of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and 5-fluorouracil (5-FU) plus folinic acid in patients with advanced gastric cancer. Paclitaxel 175 mg/m2 was given intravenously over 3 hours on days 1 and 22; folinic acid 500 mg/m2 given intravenously over 2 hours followed by 5-FU 2,000 mg/m2 given intravenously over 24 hours was administered on days 1, 8, 15, 22, 29, and 36. Six weeks of treatment were considered one cycle, and each cycle was followed by 2 weeks off treatment. Twenty-two patients (six women and 16 men) with advanced/metastatic gastric cancer were entered on trial. All patients are evaluable for response and toxicity. None had received prior chemotherapy. Radiologically metastatic sites included gastric lymph nodes (64%), liver (36%), lungs (18%), peritoneum (18%), bone (9%), and skin (5%). No complete responses were observed. Seven patients (32%; 95% confidence interval, 12% to 52%) had a partial response. Sites of partial responses included the lungs, skin, lymph nodes, and locally advanced tumor. Twelve patients (55%) had stable disease and three (14%) had disease progression. At a median follow-up of 12 months (range, 1 to 17+ months), the median overall survival for all patients was 11 months (range, 1 to 17+ months; 95% confidence interval, 6.8 to 18.2) and the median progression-free interval was 8 months (range, 1 to 13+ months; 95% confidence interval, 4.7 to 9.8). Severe nonhematologic toxicities were alopecia (45%), fever/infection (9%), diarrhea (5%), and nausea/vomiting (5%). Grade 3/4 neutropenia occurred in three patients (14%). In summary, paclitaxel given every 3 weeks in combination with once-weekly, 24-hour continuous infusions of 5-FU/folinic acid is active in advanced gastric cancer and appears to achieve response rates comparable to regimens like etoposide/folinic acid/5-FU or 5-FU/doxorubicin/methotrexate. The toxicity of this new combination is moderate and allows treatment in an outpatient setting. Ongoing studies are evaluating the activity of paclitaxel combined with weekly continuous infusions of 5-FU/folinic acid with or without cisplatin.

Adult↗
PubMed1996

Alterations of the p53 tumor suppressor gene in carcinoma in situ of the testis.

BACKGROUND: Carcinoma in situ (CIS) is regarded as the precursor of all histologic variants of testicular germ cell tumors except spermatocytic seminoma. For a variety of human malignancies, alterations of the p53 tumor suppressor gene have been identified as prognostic factors for a poor clinical course. Discussions of the occurrence of p53 gene alterations in testicular carcinoma have been controversial. Immunohistochemical detection of the p53 oncoprotein has been reported in four of eight CIS cell areas adjacent to mature teratoma. The majority of investigations have failed to demonstrate p53 gene alterations on the DNA level in testicular carcinoma specimens. However, the genetic analysis of testicular carcinoma is complicated by the histologic variety of tumors, resulting in a mixture of subtypes undergoing moleculargenetic analysis. In the present study, CIS cells identified in normal testicular tissue adjacent to different testicular tumors were examined for alterations of the p53 tumor suppressor gene. The authors believed that the detection of p53 alterations in CIS of the testis would not only support the idea of malignant potential in CIS but might also demonstrate the involvement of the p53 tumor suppressor gene in the development of germ cell cancers. METHODS: CIS cells were identified in the normal testicular tissue adjacent to 18 seminomatous and nonseminomatous germ cell tumors by histopathologic criteria and the immunohistochemical staining reaction for placental-like alkaline phos phase, a highly specific marker for testicular CIS. About 20-50 CIS cells per tumor were collected by a microdissection technique and were subjected to RNA. SSCP analysis and additional DNA-sequence analysis. RESULTS: In 12 of 18 cases (66%), RNA-SSCP analysis of the microdissected CIS cells revealed mutational band shifting at the p53 gene locus. In 7 of 18 cases (39%). the results of SSCP analysis were confirmed by DNA sequencing. DNA-sequence analysis revealed missense point mutations in the p53 gene in four cases (exon 5, codons 158, 170, and 176; exon 6, codon 213) and silent mutations in two cases (exon 5, codon 178; exon 6, codon 213). In one case, the identical missense point mutation (exon 5, codon 176) was detected in the CIS cells and also in the associated germ cell tumor. In two of six cases, different mutations were found in the CIS cells and the testicular tumor. In three cases in which DNA sequencing revealed point mutations in CIS cells, alterations of the p53 gene could not be detected in the examination of the associated tumor specimen. CONCLUSIONS: These findings appear to support the concept that malignant biologic characteristics are present in the in situ stage of testicular germ cell tumors. This is the first report demonstrating monoclonal development of a manifested testicular carcinoma from associated CIS cells on the basis of a certain mutational event in the p53 gene sequence. The involvement of p53 gene alterations in precursor cells of testicular carcinoma appears likely.

Alkaline Phosphatase↗
PubMed1996

[Late damage of curative oncologic therapy. Results of a patient sample with Hodgkin's disease and testicular tumors at the Hannover Medical School].

BACKGROUND: The present analysis deals with 2 main problems among therapy-associated late toxicities in patients after curative treatment for malignant tumors, such as Hodgkin's disease and testicular cancer: gonadal late toxicities in young patients after treatment for lymphomas and the risk of secondary neoplasia after curative treatment for malignant male germ cell tumors. PATIENTS/RESULTS: In 66 patients with Hodgkin's disease and 24 patients with non-Hodgkin's lymphomas ( < 45 years), who were in complete remission for more than 2 years after chemo- and/or radiotherapy, gonadal damages were analysed based on hormone levels (FSH, LH, testosterone, estrogen), clinical examination and patients' histories. 50% of female patients with Hodgkin's disease suffered from premature ovarian failure and 65% of men were either sub- or infertile. In contrast, only 18% of patients treated for non-Hodgkin's lymphoma showed signs of gonadal toxicity. The risk for gonadal toxicity in patients with Hodgkin's disease was related to the use of procarbacine as a part of the COPP-regimen and to infradiaphragmatic radiotherapy. Sperm conservation should be offered to male patients prior to therapy. In female patients with Hodgkin's disease hormone levels should be evaluated after therapy and substitution should be initiated early in order to avoid osteoporosis, an increased cardiovascular risk and psychological problems. In patients with testicular cancer it could be demonstrated that current therapeutic strategies are associated with a small but identifiable risk for secondary neoplasia: radiotherapy causes a 2- to 3-fold increased risk for solid cancers and chemotherapy, particularly the use of etoposide-based regimens, is associated with secondary leukemias. However, a risk-benefit analysis shows that cure rates above 80% for patients with metastatic disease will outweigh the risk of secondary neoplasia. CONCLUSION: The investigation of therapy-associated late toxicities will remain an important issue even with the use of new treatment approaches such as high-dose therapy. Prospective evaluation of late toxicities needs to be incorporated into new studies for the curative treatment of malignant tumors.

Adult↗
PubMed1996

[Cytokine therapy and the endocrine system: is it necessary to monitor more than the thyroid gland?].

UNLABELLED: Cytokines and Endocrine System: Is it Meaningful to Monitor More than the Thyroid Gland? AIM: It was the aim of this study to evaluate the occurrence, the degree, and clinical relevance of immunological phenomena in endocrine and non-endocrine organs as seen under therapy with interferon-alpha (IFN-alpha) and/or interleukin-2 (Il-2). PATIENTS AND METHODS: In 61 patients (age: 50.2 +/- 12.8 years) receiving cytokines as treatment for hepatological or hemato-oncological diseases, parameters of the thyroid gland, the gonadal system, the adrenal gland the pituitary gland, parameters of water and electrolyte-balance, and of bone metabolism were measured. All patients were treated with interferon in a mean dosage of 15.3 +/- 10.5 mio U subcutaneously per week. Additionally, 15 patients were treated with interleukin-2 (36.5 +/- 22.3 mio U subcutaneously per week). Among other assays, patients "sera were screened for the existance of autoantibodies against 30 different antigenic substrates using an indirect immunofluorescence technique (IIF). RESULTS: Pts, treated with IFN-alpha and IL-2 (n = 13) showed a significant induction of thyroid antibodies against thyroglobulin (anti-TG): 61 +/- 82 U/ml vs. 1000 +/- 2352 U/ml (p < 0.05) and against thyroid-peroxidase (anti-TPO): 162 +/- 538 vs. 468 +/- 1071 U/ml (p < 0.05). In pts, only treated with IFN-alpha (n = 26), the increase of anti-TG from 69 +/- 97 to 134 +/- 178 U/ml and of anti-TPO from 20 +/- 21 to 21 +/- 19 U/ml was insignificant. Patients with a combined treatment of IFN-alpha and Il-2 were mainly affected: 2 patients developed hypo- and 5 hyperthyroidism. Thus, regular controls of thyroid function during the entire duration of therapy is justified. We were unable to show any influence of the duration of treatment or dosage of cytokines on the endocrine and non-endocrine parameters investigated. In addition, 8 different AAB (against smooth/striated muscles, parietal cells, nuclear parts, myelin, keratin, endothel, and neuroendothel) were detected by IIF which did not change under therapy. Two patients newly developed AAB during therapy, however none of them suffered from clinical symptoms. AAB against endocrine organs other than the thyroid gland were not detected. No other endocrine system showed alterations of its function. CONCLUSION: Based on the data of this study we conclude that the thyroid gland should be regularly monitored for immunological and functional changes during cytokine therapy. The results do not support a general recommendation for a routine screening of other, non-thyroidal endocrine systems for autoimmune phenomena and alterations of function in each patient.

Adult↗
PubMed1996

The role of paclitaxel in chemosensitive urological malignancies: current strategies in bladder cancer and testicular germ-cell tumors.

Recent results demonstrate an emerging role for paclitaxel in patients with urothelial-tract cancer and in patients with testicular cancer. Yielding response rates in the range of 40-50% as a single agent, paclitaxel is one of the most active drugs in metastatic bladder cancer. Ongoing trials of paclitaxel combination chemotherapy with cisplatin or cisplatin and ifosfamide demonstrate substantial objective remission rates above 70% and, in addition, a high range of complete responses. Thus, paclitaxel appears to be an important drug when used as part of first-line combination chemotherapy for metastatic bladder cancer. Ongoing clinical trials focus on the combination of paclitaxel with cisplatin, ifosfamide, gemcytabine, and carboplatin. Furthermore, paclitaxel administration has been demonstrated to be easily applicable to patients with reduced renal function, requiring no dose reduction and producing no increase in toxicity. Future strategies will have to compare the most active paclitaxel combination regimen with first-line MVAC (methotrexate, vinblastine, adriamycin, cisplatin) chemotherapy. Finally, the role of paclitaxel combination regimens needs to be explored in the adjuvant and neoadjuvant setting in patients with bladder cancer. In testicular cancer, paclitaxel has initially been tested in patients with cisplatin-refractory disease. Among 4 consecutive trials involving a total of 83 patients a response rate of 26% has been observed using dose schedules varying from 3-h to 24-h infusions and doses ranging from 175 to 250 mg/m2. The major toxicities of paclitaxel include neutropenia, neurotoxicity, and fatigue syndrome. Currently, combinations of paclitaxel with cisplatin +/- ifosfamide are used as first- or second-line salvage therapy in patients with relapsed metastatic testicular cancer. The German Testicular Cancer Study Group uses a paclitaxel (Taxol, ifosfamide, cisplatin; TIP) combination regimen as salvage treatment. Following the TIP regimen and the application of granulocyte colony-stimulating factor (G-CSF), peripheral blood stem cells (PBSC) are harvested and the patients subsequently receive high-dose chemotherapy with PBSC rescue. Since only a few drugs have demonstrated substantial activity in cisplatin-refractory disease, paclitaxel will be used in early salvage strategies and, possibly, as first-line chemotherapy as a part of platinum-based combination regimens in patients with testicular cancer. Further trials confirming the important role of paclitaxel in this highly curable malignancy and a thorough investigation of its acute and long-term toxicity will be the future tasks.

Antineoplastic Agents, Phytogenic↗