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J T Hartmann

Publications and source records attributed to J T Hartmann.

At least 19 recordsLinked to original sources
PubMed2006

Cystatin C--a marker for assessment of the glomerular filtration rate in patients with cisplatin chemotherapy.

BACKGROUND: Cystatin C has recently been proposed as an ideal marker for glomerular filtration rate (GFR). In this study, cystatin C serum levels were evaluated in comparison to serum creatinine concentrations and inulin clearances in patients with normal kidney function receiving cisplatin-based chemotherapy to assess the validity of cystatin C as an alternative endogenous marker of GFR. METHODS: Blood samples for the assessment of cystatin C, creatinine and inulin clearances were collected in patients before and after application of cisplatin in a clinical trial. Overall, 41 patients were included in the study, 35 of them were eligible receiving cisplatin in two different cisplatin-based chemotherapy schedules. RESULTS: A 21% increase of cystatin C serum levels was demonstrated in the placebo group after application of cisplatin. Analysis of inulin clearances revealed a 23% loss of inulin clearance in patients of the placebo arm. In contrast, significant changes could not be detected by analysis of serum creatinine levels. CONCLUSIONS: Cystatin C represents a more sensitive clinical marker than serum creatinine for the early assessment of GFR damage caused by cisplatin. Changes in cystatin C serum concentrations correlate well to GFR decrease as measured by inulin clearance.

Adult↗
PubMed2006

[Chemotherapy of testicular cancer].

Platinum-based polychemotherapy has increased the cure rate in testicular cancer dramatically: at first, chemotherapy was mainly used in advanced disease. Recently it has also become common in low-stage disease, though other therapeutic options are equivalent. Risk factors might help to find the right decision. The success of treatment in patients with metastatic disease results from the combination of chemotherapy and secondary surgery. High-dose chemotherapy for patients with poor prognosis or recurrent disease is being evaluated in clinical trials. Concerning the success in these stages prognostic factors are of special importance. Patients with advanced-stage nonseminoma need residual tumor resection after chemotherapy if no complete remission could be achieved. The therapist should be aware of the indication for and schedule of chemotherapy, its side effects, and supportive care.

Antineoplastic Agents↗
PubMed2006

An open label, non-comparative phase II study of gemcitabine as salvage treatment for patients with pretreated adult type soft tissue sarcoma.

BACKGROUND: The number of effective cytotoxic agents for the treatment of patients with metastatic adult type soft tissue sarcoma (STS) is limited, when patients have failed anthracyline-based chemotherapy. The aim of this trial was to evaluate the efficacy of gemcitabine in this setting. METHODS: Between August 2001 and March 2003 19 patients were eligible to enter. Gemcitabine was administered as a 30-minutes infusion at a dosage of 1 g/m2 on day 1, 8 and 15 every 4 weeks. All patients had progressive disease during (n = 12) or shortly after an anthracycline-based regimen (n = 3). RESULTS: Four of 19 patients did not start study treatment because of fulminant progression. Fifteen patients with a median age 47 years (32-72) were assessable. All patients had received at least one prior treatment regimen (range, 1-6) for metastatic disease containing anthracyclines (n = 15) and ifosfamide (n = 11). To date, a total of 72+ cycles have been applied (median; 3, 1-28+). Seven patients (47%) had progressive disease after completion of two cycles at the first response assessment. One patient (6%) attained a partial remission, and 7 patients (47%) achieved disease stabilisations. One patient is still on treatment after more than 2.5 years. The calculated progression-free rate at 3 and 6 months was 46.7% (CI(95%), 21.4-71.9) and 13.3% (CI(95%), (0-30.5). 95% of the cycles have been applied without any dose modification or treatment delay. CONCLUSIONS: Considering response and progression-free rate as the primary endpoints for phase II trials in pretreated STS, gemcitabine has moderate efficacy.

Adult↗
PubMed2006

Multiple skeletal metastases from a giant cell tumour of the distal fibula with fatal outcome.

A giant cell tumour is a primary lesion of bone of intermediate severity. Its histogenesis is unclear. In a few cases pulmonary metastases have been described. Multiple skeletal metastases in the absence of sarcomatous change have been observed. We present a case report of a 25-year-old woman with a recurrent giant cell tumour of the distal fibula. After a second recurrence and six years after the initial diagnosis, she rapidly developed multiple bony metastases. The outcome was fatal.

Adult↗
PubMed2005

[Therapy for advanced colorectal carcinoma--new developments and standards].

Colorectal carcinoma is the second common cause of death from cancer. For a long period patients with metastatic disease were considered incurable except for a small subgroup with isolated surgically complete removable lesions in the lungs and the liver. Chemotherapy was a treatment of unproven value, beneficial in very few patients. However, in the last two decades it has become a well-documented survival prolonging treatment, postponing tumor symptoms in the majority of patients, and potentially curing some patients if combined with aggressive surgery.

Algorithms↗
PubMed2005

Adjuvant chemoradiation using 5-fluorouracil/folinic acid/cisplatin with or without paclitaxel and radiation in patients with completely resected high-risk gastric cancer: two cooperative phase II studies of the AIO/ARO/ACO.

BACKGROUND: The current two studies evaluate the feasibility, toxicity and efficacy of an adjuvant combined modality treatment strategy containing a three to four-drug chemotherapy regimen plus 5-fluorouracil (FU)-based radiochemotherapy. PATIENTS AND METHODS: Between December 2000 and October 2003, a total of 86 patients were included in both studies. Patients with completely resected gastric adenocarcinoma including a D1 or D2 lymph node dissection (LND) were eligible. Treatment consisted of two cycles of folinic acid 500 mg/m2, 5-FU 2000 mg/m2 continuous infusion over 24 h once weekly for 6 consecutive weeks, paclitaxel 175 mg/m2 in weeks 1 and 4 and cisplatin 50 mg/m2 in weeks 2 and 5 (FLPP; n=41) or two cycles of the same 5-FU/folinic acid schedule but with cisplatin 50 mg/m2 only in weeks 1, 3 and 5 (FLP; n=45). Radiation with 45 Gy plus concomitantly applied 5-FU 225 mg/m2/24 h was scheduled in between the two cycles. RESULTS: Patients characteristics were: D1/D2 LND FLP group 53%/42%; FLPP group 27%/68%; stage distribution: UICC stages III/IV(M0) FLP group 63% and FLPP group 66%. Median follow-up was 10 months (3-25) for FLP and 18 months (2-51) for FLPP patients. CTC grade 3/4 toxicities during the first cycle/chemoradiation/second cycle of FLP: granulocytopenia 3%/0/27%, anorexia 6%/10%/8%; diarrhea 8%/0/4%, nausea 3%/0/4%; FLPP: granulocytopenia 0/0/37%, anorexia 5%/11%/6%; diarrhea 5%/0/3, nausea 3%/8%/0%; early death in one patient due to Pneumocystis carinii pneumonia. Projected 2-year progression-free survival was 64% (95% CI 56% to 68%) for the FLP and 61% (95% CI 42% to 78%) for the FLPP group. CONCLUSIONS: Both chemoradiation regimens appear feasible with an acceptable toxicity profile indicating that cisplatin can be added to 5-FU/FA and that even a four-drug regimen can be investigated further in prospective clinical trials in completely resected gastric cancer patients. Treatment should be given in experienced centres in order to avoid unnecessary toxicity.

Adenocarcinoma↗
PubMed2005

Impact of tumor size on the long-term survival of patients with early stage renal cell cancer.

As the biological behaviour of even early stage renal cell cancer (RCC) strongly correlates with tumor size, it has been argued that the inclusion of RCC up to a maximum diameter of 7 cm into a common subgroup classified as T1 according to the 5th edition of the TNM system would not adequately represent the different biological aggressiveness of these malignancies. Taking this into account, the TNM classification, which now categorizes T1 RCC as T1a and T1b according to a cutoff size of 4 cm, was recently modified. However, only a few larger investigations, mainly based on univariate statistical analyses, that support the suitability of this cutoff are at present available from the literature. Therefore, it was the aim of the present investigation to determine the tumor size that best separates patients with low responses from those with high risk for tumor progression by univariate (log rank test) and multivariate (Cox regression model) statistical analyses. Between 1981 and 2000, 652 patients (443 males and 209 females) underwent tumor nephrectomy in our clinic for the diagnosis of RCC. Of these, 243 patients revealed primary tumors with a local growth not extending beyond the renal capsula at the time of surgery. For the different cutoff levels (starting from 2 cm in increments of 1 cm up to 8 cm) that were selected to subdivide the patients into groups according to the maximum tumor diameter, the correlation between tumor size and overall survival was determined by univariate and multivariate statistical analyses. It became evident that although during univariate analysis the prognostic value of a cutoff size of 4 cm was confirmed, multivariate analysis identified the highest relative risk for cause-specific death (2.93) for patients having tumors larger than 5 cm in maximum diameter. Therefore, the 5 cm cutoff seems to best determine the clinical prognosis of patients undergoing tumor nephrectomy for early stage RCC. The present study demonstrates the need for multivariate statistical approaches when the latest modification of the TNM classification system is critically evaluated.

Adult↗
PubMed2005

[Neuro-endocrine tumors of the gastrointestinal tract: epidemiology, classification, prognosis, diagnosis and therapeutic modalities].

The neuro-endocrine tumors of the gastrointestinal tract comprise a heterogeneous group of slow-growing malignancies with great differences regarding their localization, tissue of origin and their entopic and ectopic production of hormones. They can be subdivided in carcinoid tumors and endocrine tumors of the pancreas. According to their secreted products they manifest as endocrinological syndromes or as local space-occupying tumors. This review focuses, besides summarizing the available epidemiological data and describing tumor localization and classification, on the differing symptom complexes and the prognosis of the various tumor entities. Furthermore, the value of available diagnostic techniques and the role of different therapeutic modalities like surgery, radiation, biotherapy and cytostatic chemotherapy are discussed.

Carcinoid Tumor↗
PubMed2005

[Platinum compounds: metabolism, toxicity and supportive strategies].

Although the leading platinum compounds, cisplatin, carboplatin, and oxaliplatin, share some structural similarities, there are marked differences between them in therapeutic uses, pharmacokinetics, and adverse effects profiles. Compared with cisplatin, carboplatin has inferior efficacy in germ-cell tumors, head and neck cancers, and bladder and esophageal carcinomas, whereas the two drugs appear to have comparable efficacy in ovarian cancer, extensive small-cell lung cancers (SCLC), and advanced non-small-cell lung cancers (NSCLC). Oxaliplatin belongs to the group of diaminocyclohexane (DACH) platinum compounds. It is the first platinum-based drug that has marked efficacy in colorectal cancer when given in combination with 5-fluorouracil and folinic acid. Nedaplatin has been registered in Japan, whereas other derivatives, like JM216 (which is the only orally available platinum derivative), ZD0473, BBR3464, and SPI-77 (a liposomal formulation of cisplatin), are still under investigation. The adverse effects of platinum compounds are reviewed together with possible prevention strategies.

Antineoplastic Agents↗
PubMed2004

Secondary leukemia after first-line high-dose chemotherapy for patients with advanced germ cell cancer.

PURPOSE: We investigated the incidence of secondary leukemia in patients treated with first-line high-dose chemotherapy (HDCT) plus autologous stem cell transplantation (PBSCT) for advanced testicular cancer. METHODS: Three hundred and twenty-three patients who were entered into two consecutive prospective Phase-II studies of the German Testicular Cancer Study Group were analyzed. A total of 221 patients had received HD-VIP containing cisplatin, ifosfamide, and etoposide and 102 patients were treated with Tax-HD-VIP containing cisplatin, ifosfamide, etoposide, and paclitaxel, each cycle supported by autologous PBSCT. RESULTS: Patients had received a median cumulative etoposide dose of 4.9 g/m(2) (range, 2.2-9.4 g/m(2)). The median follow-up duration for all patients was 36 months (range, 0-128) with a median follow up time of 50 months (range, 0-128) for patients surviving at least 1 year after therapy. One patient developed a secondary acute myeloid leukemia (s-AML) involving a chromosomal translocation t(11;19)(q23;p13.3) 24 months after the start of chemotherapy resulting in a cumulative incidence of 0.48% [95% confidence interval (CI) 0-1.42]. Additionally, two patients with primary mediastinal germ cell cancer developed a myelodysplastic syndrome. No solid tumors had occurred. CONCLUSIONS: HDCT including high-dose etoposide with autologous PBSCT as first-line therapy for advanced testicular cancer was associated with an acceptably low risk of developing secondary leukemia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Residual tumor resection after high-dose chemotherapy in patients with relapsed or refractory germ cell cancer.

PURPOSE: To assess the role of residual tumor resection performed after high-dose chemotherapy (HDCT) in patients with relapsed or refractory germ cell tumors (GCT). PATIENTS AND METHODS: Between July 1987 and October 1999, postchemotherapy resections of residual tumors were performed in 57 patients who had been treated with HDCT for relapsed or refractory GCT and who had achieved a partial remission to this treatment. RESULTS: Complete resections of residual masses were achieved in 52 (91%) of 57 patients who were rendered disease free; in five (9%) of 57 patients, the resections were incomplete. Resection of a single site was performed in 39 (68%) of 57 patients, and the remaining 18 (32%) of 57 patients required interventions at two or more residual tumor sites. Necrosis was found in 22 (38%) of 57 patients, mature teratoma with or without necrosis was found in nine (16%) of 57 patients, and viable cancer with or without additional necrosis or mature teratoma was found in 26 (46%) of 57 patients. Viable cancer consisted either of residual germ cell or undifferentiated cancer in 22 (85%) of 26 patients, with additional non-GCT histologies in the remaining four patients. Patients with viable cancer had a significantly inferior outcome after surgery compared with patients with necrosis and/or mature teratoma even if all cancer was completely resected. Pulmonary lesions with a diameter of more than 2 cm were the only predictive variable for viable cancer in univariate analysis. CONCLUSION: Resections of all residual tumors should be attempted in patients with relapsed or refractory GCT and partial remissions after HDCT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Capecitabine in combination with mitomycin C in patients with gastrointestinal cancer: results of an extended multicentre phase-I trial.

The aim of this study was to determine the dose-limiting toxicity (DLT) and establish the recommended dose for mitomycin C added every 3 weeks to the standard combination dose of capecitabine. Cohorts of at least three patients with pretreated gastrointestinal carcinoma received capecitabine 1000 mg m(-2) orally twice daily on days 1-14 plus i.v. bolus mitomycin C on day 1 at doses of 4, 6, 8 or 10 mg m(-2) (corresponding to dose levels I-IV). Cycles were repeated every 3 weeks. Two treatment cycles were considered for the evaluation of DLTs. Of the 53 patients enrolled, the majority had colorectal (n=27) or gastric (n=14) cancers. Patients had received a median of two lines of prior chemotherapy (34% with >/=3 lines and 87% with prior 5-FU-based therapy). At the recommended dose level (IV, n=30), grade 3 adverse events during cycles 1 and 2 were: anaemia (10%); leukopenia (3%); thrombocytopenia (3%); stomatitis/mucositis (3%); hand-foot syndrome (3%). Two patients experienced DLTs (mucositis, n=1; neutropenic fever, n=1), but there were no grade 4 events. The median dose intensity for capecitabine and mitomycin C was 100% during cycles 1 and 2 and only four patients required postponement of therapy. Of the 43 patients evaluable for efficacy, seven achieved partial and minor remissions (16%; 95% CI, 5-28%), and 12 patients (28%) had stable disease. The favourable safety profile and promising activity of the capecitabine/mitomycin C combination, even in heavily pretreated patients, warrant further evaluation in patients with advanced colorectal and gastric cancers.

Adult↗
PubMed2004

Metastatic seminoma treated with either single agent carboplatin or cisplatin-based combination chemotherapy: a pooled analysis of two randomised trials.

To study the role of single agent carboplatin chemotherapy in patients with metastatic seminoma based on the data from two randomised trials. In subgroup analyses in patients with different disease characteristics, the outcome treated with either single agent carboplatin or cisplatin-based combination chemotherapy was compared. Individual patient data from two randomised European trials involving patients with metastatic seminoma were gathered. The primary endpoint for all analyses was progression-free survival. The source data of 361 patients, 184 treated with cisplatin-based combinations and 177 treated with carboplatin single agent therapy, were entered into the analysis. Patient characteristics were comparable among the cisplatin-based and the carboplatin single agent treated patient groups with lymph nodes and lungs being the most frequent metastatic sites in 92 and 8% of patients, respectively. Overall, patients treated with single agent carboplatin had an inferior 5-year overall (89 and 94%; P=0.09) and progression-free survival rate (72 and 92%; P< 0.0001) compared with patients receiving cisplatin-based combinations. For all investigated subgroups (based on age, prior radiation therapy, metastatic sites), carboplatin single agent therapy was found to be inferior to cisplatin-based combination chemotherapy. In conclusion, carboplatin single agent therapy cannot be recommended as standard treatment for any patient subgroup with advanced metastatic seminoma and cisplatin-based combination regimens remain the standard of care.

Adolescent↗
PubMed2004

Pegylated liposomal doxorubicin in combination with mitomycin C, infusional 5-fluorouracil and sodium folinic acid. A phase-I-study in patients with upper gastrointestinal cancer.

Mitomycin C (MMC) in combination with infusional 5-fluorouracil (FU) plus folinic acid (FA) is an effective treatment for metastatic gastrointestinal cancer. Anthracyclines are commonly used in the treatment of upper gastrointestinal cancer. The aim of this study was to determine the maximum tolerated dose of liposomal, pegylated doxorubicin (Caelyx) in combination with infusional 5-FU/sodium FA and MMC. Escalating doses of Caelyx (15-25-30-35 mg m(-2) corresponding to dose levels I-IV) were applied on days 1 and 29, given to fixed doses of 24-h 5-FU (2000 mg m(-2)) and sodium FA (500 mg m(-2), mixed with 5-FU in one pump) weekly for 6 weeks, and MMC 7 mg m(-2) on days 8 and 36. At least three patients were treated at each dose level. A total of 25 patients are evaluable. No dose-limiting toxicity (DLT) was observed on level I (n=3). On level II, DLT occurred in three out of five patients (mucositis and leucopenia). Owing to the early DLTs at this dose, we added a 20 mg m(-2) Caelyx dose level (Ia). In total, 17 patients were treated at this dose level. Among these, only two patients experienced DLT in cycle one and 37 complete cycles have been administered in association with a low toxicity profile. The median dose intensity was 100% for each drug during the first course and no treatment delay exceeding 7 days was required. The recommended dose of 4-weekly Caelyx in combination with weekly 24-h 5-FU/sodium FA and 4-weekly MMC is 20 mg m(-2). Preliminary antitumour activity has been observed in patients with pretreated pancreatic cancer and in untreated gastric cancer.

Adenocarcinoma↗
PubMed2004

The role of high-dose chemotherapy in relapsed germ cell tumors.

Overall, patients with relapsed or progressive germ cell tumors after cisplatin-based chemotherapy have a low chance of cure. Using conventional-dose chemotherapy (CDCT) as salvage treatment, only 15-30% of the patients will become long-term survivors. It is well known that the majority of these patients will ultimately die of their disease. Therefore, improvement of the standard treatment is clearly desirable. In the last years, high-dose chemotherapy (HDCT) has been established as an effective salvage modality. A matched-pair analysis showed an advantage for HDCT compared with CDCT with an improvement in event-free and overall survival. Furthermore, due to increasing clinical experience in the management of side-effects, the use of peripheral blood progenitor cells and the availability of hematopoietic growth factors, HDCT has become relatively safe. Therefore, HDCT should be administered in patients with first relapse and unfavorable prognostic factors, and as second or subsequent salvage treatment followed by complete resections of tumor residuals. Patients with relapse or progressive disease after HDCT who do not qualify for desperation surgery could be salvaged with palliative chemotherapy combinations using gemcitabine, oxaliplatin and paclitaxel. This report reviews the current treatment strategies and recent developments with respect to HDCT given as salvage treatment and discusses the role of prognostic factors in the management of such situations.

Antineoplastic Agents↗