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Biomedical subjects

H Wilke

Publications and source records attributed to H Wilke.

At least 19 recordsLinked to original sources
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↗
PubMed2004

[Early and late complications of chemotherapy of solid tumors].

Treatment with cytostatic agents is associated with both acute side effects such as nausea, emesis, blood count changes, and allergic reactions, and late complications such as cardiac, renal or gastrointestinal toxicity. In addition to differences in substance groups, intra-individual variations on the part of patients, and their general and nutritional status, are of particular importance for the severity of such side effects. For improved treatment monitoring, side effects should be recorded and documented in accordance with common toxicity criteria. In view of the complexity of oncological treatment, including the optimal supporting measures, such treatments should remain in the hands of oncological specialists.

Antineoplastic Agents↗
PubMed2004

High-dose chemotherapy with autologous stem cell transplantation in patients with oligometastatic breast cancer.

The purpose of this prospective trial was to study a combined-modality treatment including local consolidation by surgery or radiotherapy and high-dose chemotherapy (HDC) followed by peripheral-blood stem-cell (PBSC) transplantation. In all, 48 patients with oligometastatic breast cancer amenable to local treatment after induction chemotherapy with epirubicin and cyclophosphamide or paclitaxel and cisplatin, depending on prior adjuvant chemotherapy, were enrolled. The median follow-up was 41 months (range, 7-85 months). PBSC were collected in 47 patients, and 40 received one or two courses of HDC. Local therapy was given in 37 patients. No treatment-related deaths occurred. Of 47 evaluable patients, 36 (75% of intention-to-treat population) had no evidence of disease or complete remission after completion of therapy. Six patients (12.5%) had partial response, two patients (4%) no change, and three patients (6%) progressive disease. The median time to progression and overall survival was 17.5 (95% confidence interval (CI), 14-21 months) and 42.2 months (95% CI, 33-52 months), respectively, and 27% of patients were progression free after 5 years. In conclusion, patients with oligometastatic breast cancer can be treated safely with this combined modality protocol with promising relapse-free survivals.

Adult↗
PubMed2003

[Patient with stomach cancer with metastases. What is the value of chemotherapy?].

In comparison with supportive measures alone, chemotherapy in advanced gastric carcinoma is associated with a significant increase in survival and improvement in quality of life. The following substances are considered to be effective and suitable for combination therapy: 5-FU +/- folic acid, cisplatin, irinotecan, etoposide, taxol, and taxotere. In contrast, the effect of doxorubicin and epidoxorubicin is only moderate. Although "second generation" combinations, such as FAMTX, ELF or cisplatin/5-FU, induced higher remission rates as the "first generation" combinations, they failed to improve survival times to any appreciable extent. Currently accepted standard treatment of metastatic gastric carcinoma is infusional 5-FU + cisplatin or ECF. The third generation combinations containing taxane, irinotecan, oxaliplatin appear to be at least equally effective.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Future treatment options with capecitabine in solid tumours.

The oral fluoropyrimidine, capecitabine is attracting great interest in the context of tumour-selective therapy and rationally designed combination regimens. Agents such as taxanes upregulate thymidine phosphorylase (TP), and there is therefore a clear rationale for their combination with capecitabine. Preclinical studies of capecitabine/taxane combination therapy demonstrated synergistic antitumour activity and phase I studies showed encouraging efficacy. Therefore, a randomised, phase III trial (docetaxel versus docetaxel/capecitabine) has been initiated in anthracycline-refractory metastatic breast cancer patients. Recruitment is complete. In colorectal cancer, capecitabine/oxaliplatin combination therapy is promising and a phase I, dose-finding trial has been conducted in patients with refractory metastatic solid tumours. A similar trial has evaluated capecitabine/irinotecan combination treatment. Capecitabine is also being investigated as adjuvant therapy for colorectal and breast cancers. The primary objective of the ongoing X-ACT trial in almost 2000 Dukes' C colon cancer patients is to demonstrate at least equivalent disease-free survival between capecitabine and the Mayo Clinic regimen. In addition, the CALGB is planning a randomised, phase III trial of capecitabine versus doxorubicin/cyclophosphamide or cyclophosphamide/methotrexate/5-fluorouracil (CMF) as adjuvant treatment in high-risk, node-negative breast cancer patients aged >65 years.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

[60-year-old patient with fever, jaundice and intra-abdominal lymphomas].

BACKGROUND: Infectious mononucleosis usually manifests in adolescents and young adults. Medical history in elderly patients is often atypical and severe. CASE REPORT: We report on the medical history of a 60-year-old woman, who came into our hospital with fever, icterus, decreasing performance status and abdominal pain. Splenomegaly and multiple abdominal lymph nodes could be found by ultrasound and CT scan. Endoscopically severe mucosal alterations could be found in the upper and lower gastrointestinal tract. Serologically, an acute EBV infection was diagnosed. With symptomatic treatment, the clinical course was without any problems. CONCLUSION: Casuistically, we described the atypical medical history of an elderly patient with infectious mononucleosis. In each undefined lymphadenopathy of elderly patients, an EBV infection should be included into the differential diagnosis.

Abdominal Neoplasms↗
PubMed2001

Intradiscal pressure together with anthropometric data--a data set for the validation of models.

OBJECTIVE: To provide a database of intradiscal pressure measurements together with anthropometric data as basis for the validation of models that predict spinal loads. DESIGN: Intradiscal pressure was measured in a non-degenerated L4-5 disc of a volunteer. The anthropometric characteristics of this subject were extensively determined. BACKGROUND: Since it is usually impossible to quantify the load in the spine directly, it is predicted by various biomechanical models. However, they often cannot be validated because of the few in vivo data and missing anthropometric characteristics pertaining to them. METHODS: A pressure transducer (diameter 1.5 mm) was implanted in the nucleus pulposus of a non-degenerated L4-5 disc of a volunteer. Pressure was determined during exercises while standing, lifting activities, sitting unsupported on a stool or an ergonomic sitting ball, sitting in different postures and others. The anthropometric characteristics were determined using different tools. RESULTS: Pressure values: relaxed standing 0.5 MPa; standing flexed forward 1.1 MPa; standing extended backward 0.6 MPa; sitting unsupported 0.46 MPa; maximum values during lateral bending 0.6 MPa, during axial rotation 0.7 MPa, lifting a 20 kg weight with a round flexed back 2.3 MPa, with flexed knees 1.7 MPa, close to the body 1.1 MPa; sitting unsupported relaxed 0.45 MPa, actively straightening the back 0.55 MPa, with flexion 0.9 MPa; non-chalant sitting 0.3 MPa and others. Anthropometric characteristics with emphasis on data for the trunk are provided in tables.Conclusions. Intradiscal pressure depends on the kind of preceding activity, posture, external loads and muscle activity. RELEVANCE: The data set can be used to verify a biomechanical model adjusted to the individual characteristics by a comparison of measured and predicted intradiscal pressures.

Anthropometry↗
PubMed2001

Answering patients' needs: oral alternatives to intravenous therapy.

Metastatic colorectal cancer has traditionally been treated with i.v. 5-fluorouracil (5-FU), with or without leucovorin (LV). 5-FU is administered as either an i.v. bolus or a protracted infusion. Although schedules using the latter method offer efficacy benefits (objective response rate, time to disease progression), protracted infusion schedules are often associated with medical complications, inconvenience, high costs, and poor quality of life. Issues such as quality of life and convenience have influenced treatment decisions, but the availability of oral fluoropyrimidines represents a new development in this domain. Studies have confirmed that the majority of patients prefer oral to i.v. chemotherapy. Questionnaire-based studies have also demonstrated a preference for home-based rather than hospital-/clinic-based therapy. This preference was one of the driving forces behind the development of the oral fluoropyrimidines capecitabine (Xeloda) and uracil plus tegafur (UFT). Oral agents offer patients a more convenient treatment option that can be administered at home, providing patients with a greater sense of control over their therapy, while avoiding the medical complications and psychological distress associated with venous access. This article highlights some of the problems associated with i.v. therapy and reviews the available data on patient preference, including results of a recent, randomized, phase II study. It also provides a critical evaluation of the efficacy and safety profiles of the only two oral fluoropyrimidines approved for prescription, capecitabine and UFT/LV (UFT/LV not available in Germany and the U.S.), compared with those of two infused, 5-FU-based regimens. Finally, the results of an interactive debate exploring the opinions of approximately 400 oncologists on the issues of oral versus i.v. therapy are presented.

Administration, Oral↗
PubMed2001

Oral fluoropyrimidine-based combination therapy in gastrointestinal cancer.

Significant emphasis has been placed recently on designing more effective fluorouracil (5-FU)-based combination protocols for gastrointestinal cancer. Promising results were seen with 5-FU/leucovorin in combination with irinotecan (Camptosar) or oxaliplatin (Eloxatin), especially in colorectal cancer. Clinical trials of UFT, with or without leucovorin, demonstrate the safety of this regimen and an efficacy comparable to that of bolus 5-FU/leucovorin in the treatment of gastrointestinal tumors. Two large randomized phase III trials of capecitabine (Xeloda) showed that capecitabine also offers a convenient alternative to bolus 5-FU/leucovorin with a superior safety profile and at least equivalent antitumor activity.

Administration, Oral↗
PubMed2001

[Multimodality therapy concepts in stomach carcinoma].

The prognosis of gastric cancer is still poor even after curative R0 resection. Therefore, among various multimodality treatments a lot of phase II/III studies have been carried out evaluating preoperative chemotherapy. Although some positive results have been obtained after this procedure, neoadjuvant chemotherapy is still an experimental approach. In the future the prediction and evaluation of response must be defined more exactly. Using intraoperative radio- or intraperitoneal (hyperthermal) chemotherapy reduction of regional relapse or peritoneal carcinomatosis could be obtained without increased survival in general. According to experience in Japan adjuvant (immuno-)chemotherapy can increase the overall survival rates and even in the Western hemisphere some actual studies with adjuvant chemo- +/- radiotherapy could demonstrate a benefit of survival in patients with lymph node metastases. Nevertheless, multimodality treatment strategies must be investigated in further uniform prospective study protocols.

Clinical Trials as Topic↗
PubMed2000

[Chemotherapy in colorectal carcinoma. From "one-drug-show" to therapeutic multiplicity].

Over the past decade, the chemotherapeutic options in the treatment of colorectal carcinoma have improved considerably. Up into the nineties, chemotherapy for this condition was purely a "one-drug show", while, today, a range of effective substances and combinations are available, and these have considerably improved the prognosis of this tumour entity. Both the first and second line treatments are today firmly established. Determination of the most appropriate sequence and combination of these new drugs (primary combination therapy, sequential administration of the substances, etc.) is the subject of ongoing and planned future studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Gemcitabine and cisplatin in the treatment of advanced or metastatic pancreatic cancer.

BACKGROUND: This phase II study was initiated to determine the efficacy and safety of gemcitabine plus cisplatin in patients with pancreatic cancer. PATIENTS AND METHODS: Gemcitabine 1000 mg/m2 was given on days 1, 8, and 15 of a 28-day schedule, and cisplatin 50 mg/m2 on days 1 and 15 to chemonaive patients with locally advanced or metastatic pancreatic cancer. RESULTS: Of the 41 patients enrolled (median age 57, and 61% male), median Karnofsky performance status was 80%. Patients received a median of 4.2 cycles (range 1-11). In 35 evaluable patients, one complete response (CR) and three partial responses (PR) were observed, for an overall response rate of 11% (95% confidence interval (95% CI): 3.2% -26.7%). Stable disease (SD) > 3 months occurred in 20 (57%) patients; 6 survived > or = 1 year. Median time to progressive disease was 4.3 months (95% CI: 3.0-5.7 months). For all patients, median survival was 8.2 months (95% CI: 6.1-10.6 months) with a one-year survival rate of 27%. Therapy was well tolerated. Grade 3-4 neutropenia (no grade 3-4 infection), thrombocytopenia (no bleeding), nausea/vomiting, and alopecia were reported in 29%, 13%, and 2.6% of patients, respectively. CONCLUSIONS: The combination of gemcitabine and cisplatin is a moderately active treatment for patients with locally advanced and metastatic pancreatic cancer without compromising tolerability.

Adult↗
PubMed2000

Decision-induced focusing in social dilemmas: give-some, keep-some, take-some, and leave-some dilemmas.

Previous research on asymmetric social dilemmas has suggested that public good dilemmas evoke different choice behaviors than do resource dilemmas. The authors propose that these differences reflect a differential focus that is dependent on the way decisions are generally presented in the dilemma types. In agreement with this, the results of 2 experimental studies suggest that, in public good dilemmas, group members are less focused on the consequences of their actions for the final outcome distribution when deciding how many endowments they give to the public good than when deciding how many endowments they keep for themselves. In resource dilemmas, group members are less focused on the final outcome distribution when deciding how many endowments they leave in the collective resource than when deciding how many endowments they take.

Adult↗
PubMed2000

Colorectal cancer and metastasectomy: treatment of advanced disease.

Systemic therapy of advanced colorectal cancer has become a well established and widely accepted approach for advanced colorectal cancer. The results of prospective randomised trials have demonstrated that first and second line chemotherapy improves the outcome compared with best supportive care. With modern chemotherapy concepts, objective response rates of 30-50% and median survival times of 14-17 months can be achieved which is a step ahead in the management of this disease. Moreover, first experiences with 'preoperative' chemotherapy in technically or prognostically not curatively resectable metastases indicate that active chemotherapy regimens may offer a chance for cure in some subsets of patients with liver metastases. It is still a matter of debate whether combination chemotherapy should be used upfront in all patients or whether the same outcome can be achieved with the sequential use of the available drugs. Ongoing and planned trials dedicated to these issues (preoperative therapy, sequential or combination chemotherapy, etc.) will hopefully contribute to a more differentiated and individualised use of the available treatment options.

Antineoplastic Agents↗
PubMed2000

Induction chemotherapy followed by concurrent chemotherapy and high-dose radiotherapy for locally advanced squamous cell carcinoma of the upper-thoracic and midthoracic esophagus.

The purpose of this study was to evaluate the efficacy and toxicity of an induction chemotherapy schedule followed by high-dose radiotherapy and concurrent chemotherapy for locally advanced squamous cell carcinomas of the upper and midthoracic esophagus. Patients were treated with three courses of fluorouracil, leucovorin, etoposide, and cisplatin-containing induction chemotherapy followed by high-dose external beam radiotherapy to 65 Gy in 6 weeks for T4 and obstructing T3 tumors. Transversable T3 tumors received 60 Gy in 6 weeks by external radiotherapy, followed by two high-dose-rate esophageal brachytherapy fractions of 4 Gy in 5-mm tissue depth. Concurrent to radiotherapy, cisplatin and etoposide were given. Long-term survival of 22 patients was 41% and 31% at 2 and 3 years, respectively, with a median follow-up of 39 months. The probability of locoregional tumor recurrence was 60% at 3 years for all patients and 30% for those with a partial or complete response to induction chemotherapy. Acute toxicity of this schedule was moderate. Long-term survivors had a good swallowing function. This schedule offers a considerable chance of long-term survival for patients with locally advanced squamous cell carcinomas of the upper and midthoracic esophagus. Local in-field recurrences are the main risk after definitive radiochemotherapy. Dose escalation of radiotherapy is possible because of the observed low late toxicity.

Adult↗
PubMed2000

Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: A trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group.

PURPOSE: To compare the efficacy and tolerability of etoposide, leucovorin, and bolus fluorouracil (ELF) or infusional fluorouracil plus cisplatin (FUP) with that of the reference protocol of fluorouracil, doxorubicin, and methotrexate (FAMTX) in advanced gastric cancer. PATIENTS AND METHODS: A total of 399 patients with advanced adenocarcinoma of the stomach were randomized and analyzed for toxicity, tumor response, and progression-free and overall survival. Only reviewed and confirmed responses were considered. The analysis of remission was based on assessable patients with documented measurable lesions. The intent-to-treat principle, log-rank test, and Cox regression model were used for the statistical analysis of time-to-event end points. RESULTS: The overall response rate for 245 eligible patients with measurable disease was 9% with ELF, 20% with FUP, and 12% with FAMTX, with no significant differences. One hundred twelve patients were eligible for efficacy in assessable, nonmeasurable disease. No change was observed in 66% of patients treated with ELF, 56% with FUP, and 55% with FAMTX. Two patients achieved a complete tumor regression (one each for ELF and FAMTX). With a median follow-up time of 4.5 years, the median survival times were 7.2 months with ELF, 7.2 months with FUP, and 6.7 months with FAMTX, respectively, with no significant differences. Nonhematologic and hematologic toxicities of ELF, FUP, and FAMTX were acceptable, with neutropenia being the major toxicity for all three regimens. Seven treatment-related deaths occurred (two with FUP and five with FAMTX). CONCLUSION: All three investigated regimens demonstrate modest clinical efficacy and should not be regarded as standard treatment for advanced gastric cancer. New strategies should be considered to achieve a better clinical efficacy in the treatment of advanced gastric cancer.

Adenocarcinoma↗