Search PubMed⌕ Search

Biomedical subjects

H Kühnle

Publications and source records attributed to H Kühnle.

At least 19 recordsLinked to original sources
PubMed1997

Randomized study comparing carboplatin/cyclophosphamide and cisplatin/cyclophosphamide as first-line treatment in patients with stage III/IV epithelial ovarian cancer and small volume disease. German Ovarian Cancer Study Group (GOCA).

UNLABELLED: Several randomized studies in patients with advanced ovarian cancer have dealt with the comparison of cisplatin and carboplatin when given as either a single drug or in combination. The German Ovarian Cancer Study Group (GOCA) performed a prospective randomized trial in a subgroup of patients specified by a successful cytoreductive operation before the start of chemotherapy. From February 1987 to May 1990, 173 previously untreated patients with stage III and IV disease and limited tumor bulk of <2 cm postoperatively received either cyclophosphamide 600 mg/m2 plus carboplatin 350 mg/m2 or cyclophosphamide 1000 mg/m2 plus cisplatin 80 mg/m2. The drugs had to be administered on Day 1 every 28 days for six subsequent courses. RESULTS: In 158 assessable patients no significant differences in pathologically confirmed CR rates (pCR: 14% vs 16%), median time to progression (PFI: 19 months vs 26 months), and overall survival (OS: 35 months vs 37 months) were observed. Refusal of therapy due to toxicity was more frequent in the cisplatin arm, whereas patients with progressive disease predominated in the carboplatin arm. Nonhematologic adverse effects were more likely to occur with cisplatin whereas carboplatin patients experienced more myelosuppression. As prognostic factors associated with an increased risk of progressive disease and shorter overall survival time, stage of disease and amount of residual tumor after first surgery were determined. CONCLUSIONS: Carboplatin proved to be effective in patients with optimally debulked ovarian cancer. However, neither regimen used in this trial is sufficiently active to prevent tumor progression in the majority of patients.

Adult↗
PubMed1997

Paclitaxel combined with carboplatin in the first-line treatment of advanced ovarian cancer: a phase I trial.

Recently, a randomized study conducted by the Gynecologic Oncology Group (GOG 111) demonstrated that, given by a 24-hour infusion, the combination of cisplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is superior to combination cisplatin/cyclophosphamide in previously untreated patients with advanced ovarian cancer. This combination, however, necessitates hospitalization. Combination paclitaxel/carboplatin would be expected to induce fewer nonhematologic side effects but may be more myelotoxic. Thus, we started a phase I dose-escalation study to determine the maximal tolerated dose of paclitaxel given as a 3-hour infusion in combination with carboplatin, both drugs administered every 21 days. The paclitaxel dose was escalated by increments of 25 mg/m2, starting at 135 mg/m2 (level 1), 160 mg/m2 (level 2), 185 mg/m2 (level 3), and 210 mg/m2 (level 4). Carboplatin was administered to achieve an area under the concentration-time curve of 5, using the Calvert formula For study levels 5 and 6, the carboplatin dose was targeted at area under the concentration-time curves of 6 and 7.5, respectively, and was combined with a fixed paclitaxel dose of 185 mg/m2. Thirty previously untreated patients with stage IIC to IV ovarian cancer were enrolled. Nonhematologic toxicity, including nausea/vomiting and arthralgia/myalgia, was mild. Across all dose levels, a total of 16 patients developed peripheral neurotoxicity (World Health Organization grades 1 and 2). At dose level 5, one patient experienced reversible grade 4 neurotoxicity. Neutropenia was the principal dose-limiting hematologic toxicity. During 33 (31%) of 106 courses, World Health Organization grade 4 neutropenia was observed. Granulocyte colony-stimulating factor was required in only 7.6% of courses. Thrombocytopenia was less than that expected when carboplatin is given alone. Clinical responses were observed in eight of 14 patients, for an overall response rate of 57%. The combination of carboplatin plus paclitaxel was found to be an active regimen. This trial demonstrates that carboplatin dosed by the Calvert equation and 3-hour paclitaxel can be combined safely at full therapeutic doses for six or more courses in patients with advanced epithelial ovarian cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Preliminary results of a phase II study of epirubicin and paclitaxel as first-line treatment in patients with metastatic breast cancer.

Preliminary results of this ongoing phase II study of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) plus epirubicin administered as first-line treatment to women with metastatic breast cancer indicate encouraging response rates and no severe toxicity. Among the 57 patients admitted to this study, 52% had received prior adjuvant chemotherapy (85% with cyclophosphamide/methotrexate/5-fluorouracil), 46% had received radiotherapy, and 30% had received both forms of therapy; 63% of patients were postmenopausal, mainly with poorly differentiated tumors, and 80% presented with > or = 2 metastatic sites. Epirubicin 60 mg/m2 was administered intravenously as a 1-hour infusion followed by paclitaxel 175 mg/m2 infused over 3 hours. Standard premedication was given. Granulocyte colony-stimulating factor support was not used. Neutropenia was evident in 72% of cycles but was not severe. Instances of anemia and thrombocytopenia were rare. Alopecia was universal. All nonhematologic toxicity observed was mild or moderate (peripheral neuropathy, myalgia, nausea, vomiting World Health Organization toxicity grade < 2). At this time, 41 patients are currently evaluable for response, complete and partial remission are evident in seven and 21 patients, respectively. The overall response rate so far is 68%. An additional 12 patients show evidence of stable disease, and one has shown disease progression. Paclitaxel is considered a promising new drug in the adjuvant treatment of patients with metastatic breast cancer. Combining it with epirubicin allows safe administration with no evidence of severe cardiotoxicity. The incidence of adverse cardiac events was much lower than that observed with combinations of paclitaxel and doxorubicin.

Adolescent↗
PubMed1996

Human papillomavirus is associated with the frequent detection of warty and basaloid high-grade neoplasia of the vulva and cervical neoplasia among immunocompromised women.

A total of 158 women who either HIV-infected or under iatrogenic immunosuppression were examined regularly during a 4-year period to evaluate if certain vulvar neoplasms and cervical neoplasia have similar associated risk factors. Patients with CIN were matched prospectively with immunocompetent controls with CIN. Forty-eight cervical lesions were detected among patients, including 2 invasive carcinoma and 15 CIN-3 lesions, compared to 11 vulvar lesions, including 2 invasive carcinoma and 7 VIN-3 lesions. Women who have more than five life-time partners were more likely to have HPV-DNA positive cervical swabs and vulvar scrapes as well as cervical and/or vulvar neoplasia. Compared to 2.7% of controls 15.2% of patients with CIN had coexisting high-grade lesions of the vulva. With 1 exception all patients with vulvar neoplasia either suffered from symptomatic immunodeficiency or received immunosuppressive drugs for more than 10 years. Except for 1 VIN-3 lesions, all vulvar neoplasms were associated with HPV-DNA types 16, 31, and/or 33. Six of nine patients as well as the 2 controls with coexisting vulvar and cervical neoplasia had the same HPV-type associated with both lesions. All vulvar lesions were classified as either "warty" or "basaloid". In conclusion cervical and bowenoid/basaloid vulvar neoplasia seem to have a similar HPV-related genesis. Malfunction of the cellular immune response appears to be a cofactor in the genesis of HPV-associated neoplasia at both sites.

Case-Control Studies↗
PubMed1996

[Electrosurgical loop excision of the transformation zone in treatment of cervix neoplasia].

100 patients with CIN on referral Pap and with a distinct cervical lesion on colposcopy were treated with the loop electrosurgical excisional procedure (LEEP). Compared with 60 women who underwent cold-knife conization, the number of lesions classified as CIN-3 or more did not differ between the two groups (53% vs 53.3%). Severe haemorrhage and cervical stenosis were only observed after conization. Involvement of resection margins was found in 18% of all LEEP and in 16.7% of all cone biopsies. 3-12 months after LEEP the rate of cytologically and biopsy proven neoplasia was 2.2%. LEEP is a safe and effective procedure and should be used as the treatment of choice for distinct cervical lesions.

Biopsy↗
PubMed1996

[Taxol].

Explore the source record for details and available documents.

Antineoplastic Agents, Phytogenic↗
PubMed1995

Cyclophosphamide, methotrexate, 5-fluorouracil, and folinic acid (CMFF) as first line chemotherapy for treatment of advanced breast cancer. A pilot study.

In order to evaluate the maximum tolerable dose of a combination chemotherapy consisting of cyclophosphamide, methotrexate, 5-fluorouracil, and folinate (CMFF), 30 female patients with histopathologically confirmed, previously untreated advanced breast cancer were entered into this pilot study. Chemotherapy consisted of fixed doses for methotrexate (40 mg/m2 i.v. on day 1), 5-fluorouracil (500 mg/m2 i.v. on day 2 to 4) and folinic acid (2 x 200 mg/m2 i.v., 0 + 2 h on day 2 to 4). The dose of cyclophosphamide was escalated stepwise, starting with 200 mg/m2 i.v. on day 2 to 4, to 240 mg/m2, 290 mg/m2, 360 mg/m2 and 400 mg/m2, respectively, for each subsequent five patients. Treatment was repeated every four weeks. A total of 92 treatment cycles was given. Myelosuppression was the dose-limiting toxicity: leukopenia WHO grade III or IV was observed after a total of 28 cycles and anemia of equal intensity after 1 cycle. No thrombocytopenia WHO grade III or IV was recorded. Myelotoxicity increased with higher doses of cyclophosphamide. Among non-hematologic toxicities, alopecia was reported in two-thirds of the patients. Nausea and vomiting was noted in 25% of treatment cycles, but in one cycle only WHO grade III was recorded. No other toxicities exceeding WHO grade II occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Paclitaxel combined with carboplatin in the first-line treatment of advanced ovarian cancer.

In a phase I study to determine the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given as a 3-hour infusion in combination with carboplatin administered every 21 days to women with advanced ovarian cancer, paclitaxel doses were escalated as follows: level 1, 135 mg/m2; level 2, 160 mg/m2; level 3, 185 mg/m2; and level 4,210 mg/m2. The fixed dose of carboplatin at levels 1 through 4 was given to achieve an area under the concentration-time curve (AUC) of 5 using the Calvert formula. In levels 5 and 6 the carboplatin dose was targeted at AUCs of 6 and 7.5, respectively, combined with a fixed paclitaxel dose of 185 mg/m2. To date, 30 previously untreated patients, all with a good performance status (Eastern Cooperative Oncology Group 0 to 2) have been entered into this ongoing study. The dose-limiting toxicity of the combination was myelosuppression (leukopenia, granulocytopenia, and thrombocytopenia). Neurotoxicity was largely moderate. So far, 14 patients are evaluable for response; of these, eight (57%) showed objective (complete or partial) response and disease stabilized in six patients. No patient had disease progression. We conclude that the combination of paclitaxel 185 mg/m2 administered as a 3-hour infusion followed immediately by a 1-hour infusion of carboplatin at an AUC of 6 can be administered safely in a 21-day schedule in the outpatient setting. The recommended dose for phase III studies is paclitaxel 185 mg/m2 and carboplatin AUC 6.

Adult↗
PubMed1994

Cellular immunodeficiency enhances the progression of human papillomavirus-associated cervical lesions.

Most cases of low-grade cervical intraepithelial neoplasia (CIN) associated with oncogenic human papillomavirus (HPV) types regress spontaneously within years. Unknown co-factors seem to be necessary for a progression to malignancy. To determine the possible role of cellular immunodeficiency as such a co-factor in the genesis of genital neoplasia, 48 HIV-infected women and 52 allograft recipients were examined periodically during a 3-year period. Colposcopy, cytology and HPV-DNA typing (ViraType) were performed at each visit. Each cervical lesion was matched prospectively with 2 lesions from immunocompetent controls. In all, 29/100 patients suffered from cervical neoplasms, including 2 advanced cervical cancers and 9 CIN3 lesions. Correlation between grade of lesion and HPV DNA 16/18 was significant. Low-grade lesions among patients progressed more often than among controls and recurrent lesions after destructive treatment were seen more frequently among patients than among controls. All patients with CD4-lymphocyte counts of < 400/microliters or immunosuppression for more than 3 years suffered from progressive lesions. We conclude that malfunction of the cellular immune response following either HIV-induced depletion or iatrogenic inhibition of CD4-lymphocyte activation, enhances the progression of HPV-induced cervical lesions to malignancy.

CD4-Positive T-Lymphocytes↗
PubMed1992

[Continuous ambulatory intravenous morphine infusion for pain therapy in advanced ovarian cancer].

We report on a female outpatient with cancer of the ovary, who received continuous intravenous morphine infusion for terminal pain control. The patient was treated over a period of 48 days with a morphine dosage ranging from 10 to 60 mg/h, which kept her free of pain. With treatment, she was alert, communicative with her relatives and moved freely. At a later stage, we complemented the treatment with Diazepam and Haloperidol. No side-effects were observed over the whole period of morphine infusion.

Diazepam↗
PubMed1991

[Glassy cell carcinoma of the cervix].

Glassy cell carcinoma of the cervix is a rare carcinoma with rapid progression and early metastasis. The aggressive course of a glassy cell carcinoma of the cervix in Stage Ib (FIGO) of a 24-year-old woman could neither be markedly influenced by radical hysterectomy, nor by chemotherapy and radiation. The patient died ten months after diagnosis.

Adenocarcinoma↗
PubMed1990

Phase II study of carboplatin/ifosfamide in untreated advanced cervical cancer.

A total of 32 patients with advanced squamous-cell carcinoma of the cervix were treated with 300 mg/m2 i.v. carboplatin and 5 g/m2 ifosfamide as a 24-h i.v. infusion, both given on day 1 every 4 weeks. In all, 3 (9%) complete responses (CRs) and 19 (59%) objective responses (CR + PR) were achieved in 32 patients. Myelosuppression with leukopenia and/or thrombocytopenia of WHO grade 4 in 28% and 13% of patients, respectively, was the main toxicity. The results of our study suggest that carboplatin/ifosfamide is active as neoadjuvant treatment in advanced cervical cancer.

Adult↗
PubMed1990

[Clinical management of cystic ovarian tumors].

In a prospective study at the University of Göttingen 206 cystic ovarian tumours were examined vaginosonographically. Basing on a graduated schedule, the individual therapy of each ovarian tumour was determined. By use of this clinical management, all blastomas could be detected correctly and in 6.8% of all cases a follicle or corpus luteum cyst was operated per laparotomiam. Basing on the created data, the authors suggest a simple and effective clinical management of cystic ovarian tumours.

Adolescent↗
PubMed1989

[Results of clinical trials with the gluconeogenesis inhibitor 2-(3-methylcinnamylhydrazono)-propionate (MCHP)].

Many compounds which directly or indirectly inhibit gluconeogenesis have been described. Some of them showed hypoglycemic action in animal experiments. 2-(3-Methylcinnamylhydrazono)-Propionat (MCHP) a derivative of hydrazine demonstrated marked hypoglycemic action in animal experiments. Nontheless the administration of MCHP to type II diabetic patients showed no hypoglycemic action. Clinical or biochemical sideeffects could not be observed.

Aged↗
PubMed1986

[Postoperative therapy of epithelial ovarian cancer at the Göttingen University Gynecologic Clinic. A retrospective analysis of 82 patients 1981-1984].

An epithelial ovarial carcinoma was diagnosed and treated during 1981 to 1984 in 82 patients of the Department of Gynaecology of the University of Göttingen. The diagnostic approach and therapy are described in the paper by Grospietsch et al. [Geburtsh. u. Frauenheilk. 46 (1986), 588]. The present paper deals with the results of postoperative treatment, with particular emphasis on those factors presently considered to be prognostically relevant, such as postoperative tumour residue, age of the patient and stage of tumour spread. The results are classified according to rate of response, progression-free interval and survival time or survival rate. Analysis of the results shows that on the one hand an improvement of long-term results (survival time) has been very unsatisfactory with present-day methods--and moreover, that partly such long-term results are obtained only on the basis of an accurate diagnosis--whereas on the other hand the short-term results (tumour-free interval) together with a clear improvement of the quantity and quality of life do justify the considerable effort required by the treatment concept. Improvement of the overall result is more likely to be achieved by clinical and preclinical research towards consolidation of the primary therapy effect than by employing "trial-and-error" methods within the framework of primary therapy.

Adult↗
PubMed1986

[Current aspects of therapy of ovarian cancer. Surgical therapy of epithelial ovarian cancer at the Göttingen University Gynecologic Clinic. A retrospective analysis of 82 patients 1981-1984].

The most important step in the treatment of epithelial ovarian carcinoma is radical surgery which should be as radical as possible, since this can exercise a decisive influence on the effectiveness of subsequent chemotherapy or radiotherapy. During 1981-1984 98 patients with an ovarian carcinoma were operated upon. 82 of these patients had epithelial tumours that will be discussed in the article. The mean age was 59.9 years. 88% of the patients were additionally at risk by one or several risk factors. Surgical approach was standardised: longitudinal incision, hysterectomy, adenectomy, resection of omentum and, if necessary, maximum possible removal of the peritoneum of the pelvis. In 28 cases additional surgery became necessary at the intestine. 77% of the patients (n = 63) were in the advanced stages FIGO III and IV. In 50 patients the operation lasted for up to 4 hours, in 24 up to 6 hours and in 8 for more than 6 hours. Intraoperative complications occurred in 37% (twice lesion of the ureter, in 5 cases intestinal lesion, in 23 cases anaesthesiological problems due to preexisting risks). In stages I and II reduction of tumour size below 2 cm was achieved in 100% of the cases, in stage III in 87.5%, in stage IV in 45%. Two patients died postoperatively. The postoperative complication rate was 48%. Almost 30% of these were represented by cardiopulmonary disturbances. Although the percentage appears high, most of the problems were well manageable, so that the patients could be transferred to follow-up therapy within 2-3 weeks. For type of follow-up therapy, tumour response.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1986

[Dose calculations for local irradiation of endometrial carcinoma].

A program for a personal computer has been developed to calculate and optimize dose distributions around a high dose intracavitary afterloading applicator having a single source. The problems of the local irradiation of the endometrium-carcinoma are emphasized in connection with the optimization criteria for an adequate irradiation planing. Exemplarily, the anisotropic proportions of absorption around a special type of applicator are calculated. In addition, an algorithm for optimization of dwell times of three-dimensional arranged source positions according to a prescribed dose distribution is theoretically presented. Further, an easy way of finding isodosis by given source positions and dwell times is introduced by taking into consideration the need to superimpose the dose distribution with external radiation fields. All calculations are tested in a water phantom.

Brachytherapy↗