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Biomedical subjects

H Wilke

Publications and source records attributed to H Wilke.

At least 91 records · Page 5Linked to original sources
PubMed1993

Perspectives of surgery and multimodality treatment in gastric carcinoma.

Surgery still represents the therapy of choice for patients with primary gastric adenocarcinoma. The best survival results can be achieved if a potentially curative (R0) resection can be performed whatever the extent of resection of the primary tumor (total versus subtotal distal gastrectomy). Either procedure should be accompanied by systematic lymph node dissection since lymphadenectomy has relevant diagnostic (i.e. staging) and therapeutic implications (i.e. improved survival in stage II/IIIA disease). Since most gastric carcinomas are diagnosed in advanced tumor stages, the number of patients to be treated curatively by surgery alone remains limited. Multimodality treatment, consisting of chemotherapy and surgery, may be an encouraging alternative strategy. With actual chemotherapy protocols (i.e. 5-FU/doxorubicin/methotrexate, etoposide/doxorubicin/cisplatin) high remission rates in locally advanced irresectable lesions without distant metastases can be induced. Survival in these patients has been significantly improved after chemotherapy and second-look surgery. The effectiveness of these protocols in an adjuvant setting seems a worthwhile study for the future. In addition, immunological and somatic gene therapy may be of therapeutic impact in the next decade.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Phase II study of single-agent etoposide in patients with metastatic squamous-cell carcinoma of the esophagus.

A total of 26 evaluable patients presenting with advanced or metastatic squamous-cell carcinoma of the esophagus were entered in a phase II trial to assess the single-agent activity of etoposide. Etoposide was given at a dose of 200 mg/m2 on 3 consecutive days every 3 weeks. Five patients (19%) achieved a partial response and seven (27%) experienced stabilisation of their disease. The median duration of response was 4 months (range 3-8 months). The major toxicity was leukopenia, which reached WHO grade 3 in 46% of patients and grade 4 in 11% of cases, with five instances of leukopenic fever and one therapy-associated death being recorded. Etoposide given at this dose and on this schedule seems to have considerable activity against non-pretreated metastatic esophageal carcinoma.

Adult↗
PubMed1992

Antitumour effect and symptomatic control with interferon alpha 2b in patients with endocrine active tumours.

26 patients with progressive neuroendocrine tumours received 3 x 10(6)U/m2 interferon alfa (IFN-alpha 2b) subcutaneously thrice weekly, until progression, as outpatients with moderate toxicity. 4/16 carcinoids and none out of 10 endocrine pancreatic tumours showed objective regression. Another 17 patients (68%) had no change. For a median of 34 weeks symptom control was excellent: 9 of 17 patients had major relief from pain, 11 of 13 from diarrhoea, and 7 of 7 from flushing. Thus, low-dose INF-alpha 2b given thrice weekly might be as effective as daily treatment with higher dosages. Treatment was only administered to patients with progression or major symptoms and this did not seem to adversely affect remission quality and survival.

Adult↗
PubMed1992

A phase II study of high dose tamoxifen in progressive, metastatic renal cell carcinoma.

Thirty-four patients with progressive advanced renal cell carcinoma (RCC) were treated with high-dose tamoxifen (HD-TAM) 100 mg/m2 p.o. daily until progression. The overall remission rate was 12%, including 1 complete remission. Seventeen of the thirty-four (50%) patients had minor remission or no change. Taking into consideration the documented progression prior to tamoxifen therapy, further tumour growth could be arrested in 62% (1 CR, 3 PR, 17 MR/NC) of the patients. Median response duration for CR/PR was 20 months (range 6-21+) and median progression-free survival for MR/NC was 6 months (range 2-15). The one-year survival rate was 41%. Patients with only pulmonary metastases, good performance status and prior nephrectomy seemed to have a better survival. Side effects were comparable to those of conventional doses of tamoxifen (20-30 mg p.o. daily). These data suggest that HD-TAM may be a useful therapeutic approach with low toxicity, considering that, in metastatic RCC, the treatment intent is at best palliative.

Adult↗
PubMed1992

Interferon alpha-2b, 5-fluorouracil, and folinic acid combination therapy in advanced colorectal cancer: preliminary results of a phase I/II trial.

We conducted a phase I/II trial of 5-fluorouracil (5-FU)/folinic acid (FA) and alpha-2b interferon (IFN) in 43 previously untreated patients with measurable metastatic colorectal cancer. Patients had disease progression prior to therapy consistent of 5-FU 500 mg/m2 (level A) or 600 mg/m2 (level B) as starting dose administered as a 2-hour infusion, FA 200 mg/m2, and alpha-2b IFN 5MU/m2 subcutaneously. All drugs were given on days 1 to 5 and cycles were repeated after 3 to 4 weeks. The aim of the study was to define the maximal tolerable dose (MTD) of 5-FU for this schedule. In the absence of toxicity above MTD, defined as diarrhea and mucositis of World Health Organization grade 2 and leukopenia of World Health Organization, grade 3 5-FU was increased in increments of 100 mg/m2 for further cycles. Twenty-four patients were started on level A; 18 were started on level B. Forty-two patients were evaluable for toxicity, 32 for response. Three of 32 patients achieved a partial response; in 22 of 32 patients, tumor stabilization occurred. Forty percent of patients started on level A developed grade 2 diarrhea; 28% of patients developed grade 2 or 3 mucositis. Of 18 patients on level B, two patients experienced grade 4 mucositis (11%) and grade 3 or 4 diarrhea (11%). One drug-related death in the presence of sepsis occurred. Due to 11% of patients with grade 4 toxicity when started on 600 mg/m2 5-FU and 40% of patients with grade 2 diarrhea when started on level A, MTD as starting dose for 5-FU is 500 mg/m2 as a 2-hour infusion when used in combination with FA and IFN on a day 1 to 5 active schedule. We observed a wide range of 5-FU dose tolerated by individual patients. While some patients experienced severe, mainly gastrointestinal, toxicity on lower levels of 5-FU, others tolerated much higher 5-FU doses (11 patients, 700 mg/m2; 5 patients, 800 mg/m2; and one patient, 900 mg/m2). Our data suggest that double modulation of 5-FU by FA and IFN may not be superior to modulation of 5-FU with either drug alone.

Adult↗
PubMed1992

Biochemical modulation of 5-fluorouracil by folinic acid or alpha-interferon with and without other cytostatic drugs in gastric, esophageal, and pancreatic cancer.

5-Fluorouracil (5-FU) is one of the important antineoplastic agents for the treatment of gastrointestinal cancers. The biochemical modulation of 5-FU by various drugs has brought about the two combinations of 5-FU/folinic acid (FA) and 5-FU/alpha-interferon (IFN), which have shown clinical activity in phase II and III trials, especially in colorectal cancer. The experience with both combinations in upper gastrointestinal cancers, however, is limited. In esophageal cancer, two phase II studies with 5-FU/IFN reported seven (27%) objective remissions in 26 patients, indicating superiority of 5-FU/IFN over 5-FU monotherapy. Trials with 5-FU/FA alone are lacking in esophageal cancer. The modulation of 5-FU by IFN or FA failed to show clinically significant activity in pancreatic cancer. However, in gastric cancer, 5-FU/FA and 5-FU/IFN seem to induce higher complete and overall remission rates in advanced gastric cancer compared with 5-FU alone. With the daily times five schedule of 5-FU/FA, 27% objective remissions were achieved; in combination with other cytotoxic drugs, such as etoposide, anthracyclines, cisplatin, mitomycin, or methotrexate, objective response rates up to 50% and more were reported.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

New developments in the treatment of gastric carcinoma.

The recent successes being achieved with combination chemotherapy regimens strongly indicate that gastric cancer is chemosensitive. With these regimens, objective remission rates of more than 50% were recorded, including approximately 10% complete remission (CRs). The finding that locally advanced disease (LAD) and technically unresectable disease could be rendered resectable by preoperative chemotherapy (EAP) was important. The median survival time was 18 months for all patients and 24 months for disease-free patients. At 30+ months, 21% of all patients are still living disease free. The expected survival of patients with unresectable LAD is approximately 4-6 months without any treatment and 6-9 months with standard chemotherapy. Compared with the latter results, the preoperative use of etoposide, adriamycin, and platinum (EAP) seems to improve the prognosis of patients with LAD. Moreover, such a multimodal approach may increase the number of long-term survivors among patients with resectable gastric cancer, especially those whose stage indicates a high risk of relapse (stage IIIa or IIIb). However, partly because of the severe toxicities (myelo-suppression, nausea/vomiting), a considerable number of patients cannot be treated with these new regimens. Considering the predominantly palliative treatment intentions in far-advanced (metastasized) gastric cancer, regimens with low toxicities and acceptable activity should be preferred. For these reasons, we developed and investigated the combination etoposide, leucovorin, and 5-FU (ELF) in a phase II trial in elderly patients (greater than 65 years) and in patients with cardiac risks who could not be treated with anthracyclines. The overall response rate in 51 evaluable patients was 53%, including six clinical CRs (12%). The median remission duration was 9.5 months and the median survival time was 11 months. Tolerability was excellent. The high remission rate and long medical survival time achieved with ELF, plus its good tolerability, make this combination a valuable alternative to anthracycline-containing regimens. In addition to developing new treatment plans and strategies, it is also desirable to predict treatment outcome with an acceptable degree of certainty. Combinations of variable defined patient subgroups with significantly different probabilities for achieving objective response and for survival. The results of this analysis may contribute to a more patient-oriented and risk-adapted chemotherapy and to better comparability of future studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Etoposide, folinic acid, and 5-fluorouracil in carboplatin-pretreated patients with advanced gastric cancer.

A group of 20 patients with gastric cancer, refractory to or with no change after two or three cycles of carboplatin were treated with etoposide/folinic acid/5-fluorouracil (ELF). An objective remission rate of 45% (9/20), a median remission duration of 8 months and a median survival time of 11 months were achieved. Toxicities were mild to moderate only. These results are comparable to those being achieved with ELF in previously untreated gastric cancer patients and confirm its efficacy and good tolerability.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Cisplatin, etoposide, and ifosfamide salvage therapy for refractory or relapsing germ cell carcinoma.

Thirty patients with metastatic progressive germ cell carcinoma who failed to be cured with first-line cisplatin chemotherapy were treated with a salvage regimen consisting of cisplatin 20 mg/m2, etoposide 100 mg/m2, and ifosfamide 1.2 g/m2 (PEI) intravenously (IV), days 1 to 5 every 3 weeks. Ten patients (33%) were tumor-free at the end of therapy. Complete response (CR) was achieved with chemotherapy alone in four patients and with additional surgery in six patients (two necroses, two mature teratomas, two carcinomas). Six patients (20%) had normalization of tumor markers but unresectable residual disease (Rm-), and the remaining 14 patients (46%) failed to respond. Of 10 patients with CR, nine (90%) relapsed again (eight carcinomas, one mature teratoma). The median duration of CR was 3.5 months. The median survival of the whole group was 311 days (range, 110 to 996+). Currently, seven of 30 patients are alive, and five of them are without signs of progressive tumor. The response to prior cisplatin therapy predicted for response and survival after PEI salvage therapy. Of 14 patients with prior CR, eight (57%) achieved a second CR compared with one of 11 (9%) with prior unfavorable response (P = .039). The median survival for patients with prior favorable response was 400 days, compared with 251 days for patients with prior unfavorable response (P less than .001). Myelosuppression was dose-limiting, with leukopenia greater than grade 2 in 84% and thrombocytopenia greater than grade 2 in 51% of all cycles. This three-drug regimen can induce a second CR in one third of patients with relapsed or refractory germ cell carcinoma. Only those patients with prior favorable responses can expect to be cured by this salvage regimen, while patients with prior unfavorable response should be considered for alternative salvage approaches.

Adult↗
PubMed1991

Megestrol acetate in cancer cachexia.

This randomized, controlled trial assessed the activity, tolerance, and degree of weight gain and anorexia of two doses of megestrol acetate in patients with advanced cancer and cachexia. Patients received either 480 mg/d or 960 mg/d megestrol acetate or placebo for 8 weeks. As of June 1990, 55 patients had been randomized; 16 died during the 8-week study, and it was too early to evaluate another 5 patients. The remaining 34 patients were included in analyses. The median initial weight loss ranged from 15% to 22% of usual body weight, which shows the severe degree of malnutrition. Further weight loss was seen in 6 of 8 patients in the placebo group compared with only 5 of 15 and 3 of 11 patients in the low-dose and high-dose megestrol acetate groups, respectively. The median further weight loss was comparable in all groups. Six of 15 and 6 of 11 patients in the low-dose and high-dose groups, respectively, gained weight with a median of 3 kg and 4 kg, respectively. A trend showed beneficial effects of megestrol acetate. Appetite improvement was similar in all groups. Due to the small sample size, however, there were no statistically significant differences among the three groups. Side effects of megestrol acetate were mild. In a subgroup of 15 patients, measurement of body water content indicated a decrease of body fat after 8 weeks in the placebo and low-dose groups. Only the high-dose megestrol acetate group showed an increase in both fat and lean body mass, suggesting a positive effect.

Adult↗
PubMed1990

Mitoxantrone, cytosine arabinoside, and VP-16 in 36 patients with relapsed and refractory acute myeloid leukemia.

Mitoxantrone in combination with VP-16 proved to be effective in refractory and relapsed acute myeloid leukemia (AML), with 42% of patients achieving complete remission (CR). The aim of this study was to assess whether the addition of cytosine arabinoside increased the response rate at a tolerable toxicity. The regimen consisted of mitoxantrone (M) 10 mg/m2 i.v. days 4-8, cytosine arabinoside (A) 100 mg/m2 continuous infusion days 1-8, and etoposide (VP-16) (V) 100-120 mg/m2 i.v. days 4-8 (MAV protocol) for relapsed and refractory AML. Thirty-six patients were treated, with a median age of 51 (20-73) years. For induction therapy one to two MAV cycles and for consolidation therapy two courses were scheduled. Twenty-one (58.3%) patients attained a complete remission (CR), with a median duration of 4.5 (1-12+) months. The median survival of all patients was 5.5 (0.5-15.5+) months. Four patients died in CR from chronic infections or after consolidation therapy with MAV. In evaluable patients, times to greater than 500 granulocytes/microliters and greater than 25,000 platelets/microliters were 23 (7-46) and 23 (6-44) days, respectively. In 54 evaluable MAV courses the following toxicity was observed (WHO grades 3/4): 26%, nausea and vomiting: 9%, hemorrhage; 6%, bilirubinemia; 11%, diarrhea; 22%, mucositis; 6%, local infection; 20%, septicemia; 13%, fever of unknown origin; 2%, cardiac arrhythmia; 7%, congestive heart failure. We conclude that MAV therapy is a highly active antileukemic combination with acceptable toxicity, which is recommended for further clinical trials in untreated AML.

Adult↗
PubMed1990

Comparative activity of four anthracyclines against heterotransplanted germ cell tumor lines.

Though the majority of patients with metastatic nonseminomatous germ cell tumors can be cured by modern combination chemotherapy, for those patients who do not respond to standard therapy additional drugs are needed. The activity of three new anthracycline derivatives, 4-epidoxorubicin, THP-doxorubicin and mitoxantrone against two established human testicular cancer cell lines in comparison to doxorubicin and to cisplatin, vinblastine, bleomycin and ifosfamide was studied in a xenograft model. All drugs were given at equitoxic doses. There were no differences in antitumor activity between the four anthracycline derivatives. In line H 12.1, which is very sensitive to the standard drugs cisplatin, vinblastine, bleomycin and ifosfamide, all four anthracycline derivatives were inferior to these agents. In contrast, in line H 23.1, where all four standard agents showed a significant lower antitumor activity when compared to line H 12.1, the anthracyclines preserved their activity, indicating a lack of cross resistance. Thus the anthracycline derivatives seem to be inferior to the standard drugs as first line treatment but because of apparent lack of cross resistance they deserve further evaluation in refractory germ cell tumors.

Animals↗
PubMed1990

High dose folinic acid/etoposide/5-fluorouracil in advanced gastric cancer--a phase II study in elderly patients or patients with cardiac risk.

Thirty-four consecutive patients with measurable advanced gastric cancer were treated in a disease oriented Phase II study with high-dose folinic acid (HDFA) 300 mg/m2 10 min. inf., followed immediately by etoposide 120 mg/m2 50 min. inf., followed immediately by 5-fluorouracil (5-FU) 500 mg/m2 10 min. inf., given on day 1,2,3 (ELF). Courses were repeated every 22-28 days. All patients who entered this study were older than 65 years or had underlying cardiac disease. Thirty-three patients were evaluable for response and toxicity (greater than or equal to 1 course). One patient was lost to follow up. The overall response rate was 48% (16/23) including 12% (4/33) complete remissions. Eight patients had minor responses or no change and 9 had progressive disease. Five of six patients with locally advanced and non-resectable disease had an objective response (1 CR, 4 PR's). The response rate in patients with metastatic disease was 41% (11/27). After a median observation time of 6.5 months, the median survival time was 10.5 months, with a median remission (CR + PR) duration of 8 months. Toxicity was manageable and included mild to moderate myelosuppression and gastrointestinal toxicities. One episode of life-threatening (Grade IV) leukopenia, and two episodes of severe diarrhea requiring hydration were noted. No treatment related death occurred. ELF is an effective combination in advanced gastric cancer and can be safely administered to elderly patients and patients with cardiac risk.

Aged↗
PubMed1990

Activity of cytostatic drugs in two heterotransplanted human testicular cancer cell lines with different sensitivity to standard agents.

Two established human testicular cancer cell lines were used in a mouse xenograft model to assess the antitumour activity of 15 anticancer agents. Line H 12.1 was highly sensitive to cisplatin, bleomycin and vinblastine, resembling non-pretreated testicular tumours, whereas line H 23.1 showed resistance to cisplatin and vinblastine, comparable to tumours with acquired or intrinsic drug resistance. In line H 12.1 several drugs were highly active, including cyclophosphamide, ifosfamide, nimustine and vincristine; carmustine, vindesine, doxorubicin, epidoxorubicin, pirarubicin, mitoxantrone, carboplatin and iproplatin had only moderate activity. In line H 23.1 only cyclophosphamide, ifosfamide, nimustine, vincristine and bleomycin had antitumour activity. These two cell lines represent a useful model for preclinical evaluation of new agents with presumed activity in testis cancer.

Animals↗