Biomedical subjects

K Bertelsen

Publications and source records attributed to K Bertelsen.

At least 37 records · Page 2Linked to original sources

PubMed1993

Long-term follow-up of patients with advanced ovarian carcinoma treated with chemotherapy.

BACKGROUND: The evolution of the management of advanced ovarian carcinoma over the last fifteen years has resulted from a number of well-designed randomized trials involving large numbers of patients. MATERIALS AND METHODS: A critical review of long-term follow-up of patients entered onto eleven major randomized trials of advanced ovarian carcinoma has been performed. RESULTS: In the pre-platinum era no long-term survival benefit was obtained with combination compared with single agent chemotherapy. When adding cisplatin to front-line therapy at least a short-term gain in terms of superior response rate and progression-free intervals is obtained compared with non-cisplatin combination chemotherapy. Survival data are more difficult to assess due to the use of cisplatin-containing salvage therapy. Cisplatin-based combination therapy also offers enhanced patient benefit when compared with cisplatin alone. A slight advantage favouring anthracycline-containing therapy is observed, whereas no advantage is obtained with alternating cisplatin and non-cisplatin regimens or by adding BCG. CONCLUSIONS: Platinum-based combination chemotherapy is clearly associated with improved response rates and progression-free survival and, at least in some studies, better overall survival. At least six cycles of therapy should be given. Such approaches should yield long-term survival rates of 10% or better for patients with large-volume disease and 20% or better for small-volume disease.

Antineoplastic Agents↗

PubMed1993

Advanced epithelial ovarian cancer: 1993 consensus statements.

BACKGROUND: Over the last few days of a 5-day international workshop held in June 1993, a group of specialists in the field of advanced epithelial ovarian cancer tried to reach consensus on a number of issues with implications for standard practice and for research. METHODS: Five groups of experts considered several issues which included: biologic factors, prognostic factors, surgery, management recommendations, dose intensity, supportive care, drug resistance, second-line treatment, investigational drugs, and tumour markers. Discussing the management recommendations, the group attempted to arrive at answers to four questions: Is there in fact a cure rate for advanced ovarian carcinoma? Are there prognostic factors which help to identify patients who will not do well with current therapy? What is the current best therapy for advanced ovarian carcinoma? What directions should research take in advanced ovarian cancer? In a plenary meeting these issues were discussed. RESULTS: Consensus statements were achieved on all topics mentioned above. This article reports on the statements written by the chairmen and approved by the consensus group.

Antineoplastic Agents↗

PubMed1993

Radiotherapy for gynecologic cancer.

The past year has not seen any breakthroughs in radiation treatment of gynecologic cancer. In reference to cervix cancer, important contributions concerning side effects and the role of radiosensitizers were published. The lack of randomized trials dealing with adjuvant radiotherapy is obvious. Improvement based on technical progress can be expected. For ovarian cancer, an important review about whole abdominal irradiation as adjuvant therapy was published. The long-term complication rate of whole abdominal irradiation is acceptable, but whether adjuvant whole abdominal irradiation has an effect upon survival superior to that of chemotherapy is still discussed. Combined treatment with chemotherapy and radiation therapy for advanced ovarian cancer is feasible, but there is no proof that the addition of radiotherapy improves survival. Literature about endometrial cancer was scarce in 1992 and did not contribute to the major question: Does adjuvant radiotherapy have any effect in endometrial cancer?

Endometrial Neoplasms↗

PubMed1993

A randomized feasibility study evaluating the effect of radiotherapy alone or combined with 5-fluorouracil in the treatment of locally recurrent or inoperable colorectal carcinoma.

The effect of radiotherapy alone or given simultaneously with 5-FU in the treatment of locally recurrent or inoperable colorectal carcinoma was investigated in a randomized feasibility trial. Twenty-nine patients were randomized to radiotherapy alone (50 Gy/5 weeks + 10-20 Gy boost), and 30 patients to the same radiotherapy with weekly 5-FU (600 mg/m2) given before treatment every Monday during the first 5 weeks. The two groups were comparable with regard to age, sex, previous treatment, symptoms, tumour size and performance status. Treatment compliance to radiotherapy was the same in both groups with 87% receiving at least 50 Gy. Drug treatment was completed in 18/30 patients. Overall the treatment resulted in a significant palliative effect in 73% of evaluable patients with a median duration of 26 months, and objective response in 32% (8 CR, 11 PR), with a median duration of 18 months. The 3-year actuarial survival rate was 9% (median 12 months). Only patients who achieved CR became long-time survivors (63% 3-year actuarial survival). Similarly, performance status had a strong association with survival. Multivariate analysis showed complete response and high performance status to be the only parameters having prognostic influence on survival. Addition of 5-FU did neither influence the objective or symptomatic response, nor the development of distant metastases. However, addition of the drug resulted in an apparent increase in the frequency of severe acute radiation complications (33% vs. 13% after irradiation alone).

Adult↗

PubMed1993

Advanced ovarian cancer. Dose intensity.

BACKGROUND: The rationale for dose intensity is based on pre-clinical observations in experimental model systems of cancer as well as upon retrospective studies correlating the impact of dose intensity upon response rates and survival. MATERIALS AND METHODS: A review has been performed based on trials attempting to compare the effects of two different dose intensities of either cisplatin or carboplatin, combinations of cisplatin and carboplatin, combined platinum with additional agents, and high-dose chemotherapy, regimens requiring hematologic support. RESULTS: The early phase II trials suggested that there may be an important dose response range over clinically achievable platinum doses, but randomized trials have failed to consistently show a clinically significant improvement with high-dose therapy. Reasons for this may be differences in patient selection, that total dose is the most important factor, or that a more than two-fold increase in dose intensity is needed to detect differences in response and survival rates. Phase I and II studies indicate that high, but short lasting, response rates can be achieved with high-dose therapy with haematopoietic support in refractory patients, but the toxicity is substantial. Paclitaxel dose intensity is presently being studied in several trials. CONCLUSIONS: Future trials of dose intensity should be focused upon patients with small volume disease and drug sensitive tumours.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

High-dose platinum chemotherapy in advanced ovarian cancer: a phase II study.

From September 1986 to November 1988, 38 patients with previously untreated ovarian cancer, FIGO stages III and IV, were allocated to a study testing the efficacy of high-dose platinum delivered as combined carboplatin and cisplatin. The regimen was as follows: Day 1, 250-350 mg/m2 carboplatin and 500 mg/m2 cyclophosphamide, Day 15, 100 mg/m2 cisplatin. Overall clinical response was 60%, and complete pathologic response, verified at second-look laparotomy, was 24%. Median survival was 17 months and 3-year survival 27%. The results are similar to those obtained by a standard dose of cisplatin, cyclophosphamide, and doxorubicin. Myelotoxicity was dose limiting. After receiving four cycles, 44% of patients had grade 3 or 4 leucopenia and 65% had grade 3 or 4 thrombopenia. Despite this, dose intensity of combined cisplatin and carboplatin was between 30 and 45 mg/m2/week, expressed as cisplatin by assuming that 1 mg cisplatin equals 4 mg of carboplatin. A correlation between dose intensity and response was not found. In conclusion the study showed that the regimen is feasible, but very myelotoxic. The results were not superior to those obtained by combination chemotherapy using standard doses of cisplatin.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

Time to loco-regional recurrence after resection of Dukes' B and C colorectal cancer with or without adjuvant postoperative radiotherapy. A multivariate regression analysis.

Factors influencing time to loco-regional recurrence were identified in a multivariate regression analysis of data from a series of 468 radically operated patients (260 Dukes' B and 208 Dukes' C) with carcinoma of the rectum and the rectosigmoid. A number of clinical and pathological characteristics were prospectively collected and recorded. In addition, carcinoembryonic antigen (CEA) was measured within 1 week before surgery. The endpoint used was recurrence below the level of the umbilicus. All patients were followed for at least 5 years or until time of death. The two Dukes' stages B and C were analysed in two separate analyses using the Cox proportional hazards model. In patients with Dukes' B tumours, an increased risk of loco-regional recurrence was associated with perineural invasion, tumour located less than 10 cm from the anal verge, patient aged above 70 years, and small tumour size. In patients with Dukes' C tumours, the necessity to resect neighbour organs, perineural and venous invasion, tumour located less than 10 cm from the anal verge, and large tumour size were all associated with a poor loco-regional outcome. Postoperative radiotherapy was not a significant prognosticator for loco-regional control. An update of the 5-year results of the randomised study of post-operative radiotherapy (50 Gy with 2 Gy per fraction in an overall treatment time of 7 weeks) showed no survival benefit from adjuvant radiotherapy in either Dukes' category and no statistically significant improvement in the 5-year loco-regional control rate. However, when the comparison was restricted to a group of high-risk patients there was a statistically significant benefit from radiotherapy with respect to loco-regional control (P = 0.03) but not with respect to survival (P = 0.23). The potential advantage, in terms of the required number of patients, of restricting clinical trials of intensified loco-regional therapies to the high-risk patients, is illustrated.

Adult↗

PubMed1992

A multicenter phase II study of carboplatin in advanced ovarian carcinoma: final report.

A phase II trial of single-agent carboplatin in advanced ovarian cancer was performed by 19 institutions from 10 European countries. A total of 260 patients were treated, with a median age of 55 (range: 20-79) years. Karnofsky performance status was 80-100 in about two-thirds of the patients. Prior therapy consisted of surgery only in 31 patients, irradiation in 9, chemotherapy without cisplatin in 45, and with cisplatin in 175. Carboplatin was administered as second-line therapy in about one-half and as third-line or more in one additional third of the study population. Initial dose was 400 mg/m2 in 90, 360 mg/m2 in 152, and 320 mg/m2 or less in 18 patients. A total of 971 courses (mean 3.7, median 2, range: 1-13) of therapy were administered. A total of 16 complete and 46 partial responses were observed in 226 evaluable patients, for an objective response rate of 27%. Efficacy was greater in chemotherapy-untreated patients (51% vs. 23%, p = 0.002). In cisplatin-pretreated patients activity was significantly higher in non-refractory patients (26% vs. 4%, p = 0.015). Myelosuppression was the most significant side effect. However, low hematologic counts seldom translated into clinically significant complications. Patients with impaired baseline creatinine clearance and poor performance status were at higher risk of developing severe myelosuppression during the initial course of treatment. Non hematologic side effects were rare and mild, except for emesis. Carboplatin has a definite role in the treatment of ovarian cancer, but almost complete cross-resistance with the parent compound was observed clinically.

Adult↗

PubMed1992

Causes of death during the first 5 years of a randomized trial of mass screening for colorectal cancer with fecal occult blood test.

The main purpose of population screening for colorectal cancer is to reduce mortality from the disease. The criteria of death from colorectal cancer are defined in the present randomized trial of 61,938 persons between 45 and 74 years old, and the need for an impartial death review committee was demonstrated. Causes of death within the first 5 years are described within subgroups of the test group and compared with those in the control group. Death rates were higher among non-responders to screening than among controls and among those in whom Hemoccult-II had been performed at least once. Persons with negative Hemoccult-II had a lower death rate than controls. The overall autopsy rate was 32%. Lethal complications from treatment of colorectal neoplasia were evaluated per se. Death from colorectal cancer occurred in 74 persons in the total screening group and in 91 among controls. Sources of bias are discussed. A method of evaluating possible benefit to those being screened is suggested. Final results cannot be expected before 1996.

Aged↗

PubMed1992

Weekly oral idarubicin in advanced prostatic cancer. A phase II study.

Twenty-five patients with advanced prostatic cancer progressing after one course of endocrine treatment entered a phase II study of weekly administration of 30 mg Idarubicin orally. Twenty-two patients were evaluable for response and partial response (PR) was noted in 2 patients and stable disease (NC) in 10 patients. Median survival was 31 weeks and median time to progression was 14 weeks. Twenty-three patients were eligible in a score system combining analgetic consumption and pain reduction measured on a Visual Analogue Scale (VAS) and 30% achieved a subjective response. Fifteen patients fulfilled treatment with the planned dose and 10 patients had dose reduction to a median of 23.8 mg Idarubicin. Haematological toxicity was greater than or equal to grade 3 (WHO) in 20% of the patients. Non-haematological toxicity was dominated by nausea/vomiting with 48% grade 3 (WHO). In conclusion, Idarubicin seems of limited value in the treatment of patients refractory to first line endocrine treatment.

Administration, Oral↗

PubMed1991

[Treatment of cervix cancer in Denmark].

The current status of cervical cancer treatment in Denmark is discussed. Diagnostic aspects and problems of classification are presented briefly supplemented with a comment on new prognostic parameters based on a semiquantitative score system and flow cytometry. Surgery is the treatment of election for the early stages whereas radiotherapy is the treatment of choice in advanced stages. Chemotherapy should only be employed in the framework of clinical trials. It is concluded that centralised treatment should be maintained.

Denmark↗

PubMed1991

Protocol allocation and exclusion in two Danish randomised trials in ovarian cancer.

Between September 1981 and November 1984 the Danish Ovarian Cancer Group (DACOVA) performed two randomised trials. One for adjuvant therapy in stages Ib, Ic and II and one for chemotherapy treatment in stages III and IV. One hundred and twenty patients fulfilled criteria for the early stage protocol but only 60% was randomised. Three hundred and sixty-one fulfilled criteria for the advanced stages protocol, 73% was randomised. In early stages 11% were excluded because of unavoidable reasons and 29% because of avoidable reasons. In contrast, in advanced stages 21% were excluded because of unavoidable reasons and only 6% because of avoidable reasons. Allocation to the early stage protocol varied with stage, histologic type, residual tumour, and the presence of ascites. These factors had no influence upon allocation to the advanced stages protocol. The experience from this study is: only essential and simple questions should be examined in multicentre trials. Patient accrual and the difference between randomisation groups are usually overestimated, large scale trials are often required to get statistically significant differences, and the participation of departments only randomising a small and selected part of their patients is questionable.

Carcinoma↗

PubMed1991

Malignant mixed müllerian tumors of the ovary. Report of 13 cases.

Thirteen patients with verified malignant mixed Müllerian tumor of the ovary treated in Denmark during the 7-year period 1981-87 were reviewed. Two patients had homologous and 11 patients had heterologous tumors. Four patients with early stage disease underwent radical surgery; 9 patients had stage III disease. Median survival for all 13 patients was 12 months. Six patients received platinum-containing cytotoxic therapy; 2 of these patients without measurable disease became long-term survivors (survival times 42+ and 92+ months, respectively) and 3 of the 4 remaining patients with evaluable disease obtained an objective remission.

Aged↗

PubMed1990

Tumor reduction surgery and long-term survival in advanced ovarian cancer: a DACOVA study.

Three hundred sixty-one patients with FIGO stage III and IV ovarian cancer were treated with cis-platinum combination chemotherapy in a Danish multicenter trial. Primary surgery was performed at 58 different departments; 32% of the patients were operated at a department associated with an oncologic center, 50% at a general gynecologic department, and 18% at a general surgical department. Complete pathologic response and long-term survival were similar for patients operated on in the different departments. Patients who underwent radical surgery or optimal debulking had a 10% risk of progression during chemotherapy and a 5-year survival of 46%. Patients who underwent suboptimal debulking and exploratory laparotomy had a 40% risk of progression during chemotherapy and a 5-year survival of 14%. Complete pathologic response showed an insignificant difference between radical surgery and optimally tumor reduction (57% versus 41%) and a significant difference between suboptimal tumor reduction and exploratory laparotomy (19% versus 6%). Patients secondarily tumor reduced had a survival rate superior to that of patients not secondarily tumor reduced (25% versus 4% at 4 years).

Adenocarcinoma↗

PubMed1990

Intraperitoneal carboplatin in the treatment of minimal residual ovarian cancer.

Thirty-one ovarian cancer patients with minimal residual disease after intravenous cisplatin combination chemotherapy were treated with intraperitoneal carboplatin (IP-Ca). The dose of IP-Ca was escalated from 150 to 350 mg/m2. Twenty-two patients received at least three courses of IP-Ca and were evaluable for efficacy. Third-look laparotomy was done in 10 patients. Two patients obtained a complete pathological response (CPR) lasting 33+ and 41+ months, respectively; 8 patients had minimal residual disease. Median survival for all patients was 14+ months. All patients were eligible for toxicity. Maximum tolerable dose in these heavily pretreated patients was 300 mg/m2 IP-Ca. The dose-limiting toxicity was thrombocytopenia; in 27% of the patients who received 350 mg/m2 IP-Ca, WHO grade 4 thrombocytopenia was seen. No patient had WHO grade 4 leukopenia. Subjective side effects consisted of mild nausea and vomiting (WHO). In conclusion, IP-Ca can produce CPR in heavily pretreated patients with only minor side effects.

Adult↗

PubMed1990

Teniposide in recurrent or advanced cervical carcinoma: a phase II trial in patients not previously treated with cytotoxic therapy.

Thirty-two patients with advanced or recurrent cervical cancer were entered into this study of single-agent teniposide as first-line chemotherapy at a dose of 100 mg/m2 intravenously on Days 1-3 every 3 weeks. Of these patients, 7 (22%) had a partial response to therapy; no patient had a complete response. Median time to treatment failure was 13 weeks [95% confidence limits (CL): 10-21 weeks] and median survival was 28 weeks (95% CL: 14-43 weeks). Toxicity was moderate. Leukopenia and thrombocytopenia (WHO grade 3 or 4) was noted in 9 patients and 1 patient, respectively. Nausea and vomiting were mild. Seventy-five percent had alopecia requiring a wig. There were no treatment-related deaths. This study indicates that teniposide has some, although limited, activity in cervical cancer.

Adult↗

PubMed1990

Randomized study of whole-abdomen irradiation versus pelvic irradiation plus cyclophosphamide in treatment of early ovarian cancer.

From 1 September 1981 to 1 January 1987, 118 patients with FIGO Stage IB, IC, IIA, IIB, and IIC epithelial ovarian cancer were randomized to abdominal irradiation or pelvic irradiation + cyclophosphamide. There was no difference between the regimens with respect to recurrence-free survival (55%) and 4-year overall survival (63%). At routine second-look laparotomy, 16% of patients without clinical detectable tumor showed recurrence. Twenty-five percent of the patients treated with pelvic irradiation + cyclophosphamide had hemorrhagic cystitis, probably caused by radiation damage and cyclophosphamide cystitis. Eight percent had late gastrointestinal symptoms requiring surgery.

Abdomen↗

PubMed1990

Blood transfusion and prognosis in Dukes' B and C colorectal cancer.

To evaluate the prognostic influence of blood transfusion in cancer patients, transfusion data were reviewed on 468 radically operated patients (260 Dukes' B and 208 Dukes' C) with carcinoma of the rectum and the rectosigmoid. Data on whole blood and packed red blood cell transfusions were recorded together with a number of clinical, pathological and histochemical characteristics. The endpoint used was death with cancer. All patients were followed for 2-7 years or until time of death. Univariate statistical methods revealed a highly significant trend towards worsened prognosis with increasing volume of transfusion blood. However, this effect was insignificant when multivariate statistical methods were employed: patients receiving whole blood or packed red blood cell transfusions did no worse than expected from their clinico-pathological characteristics. It is concluded that in this series the observed association between transfusion status and prognosis is adequately explained by a multivariate prognostic model including well-established prognostic factors.

Aged↗