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Biomedical subjects

K Karrer

Publications and source records attributed to K Karrer.

At least 19 recordsLinked to original sources
PubMed1995

Surgery for cure followed by chemotherapy in small cell carcinoma of the lung. For the ISC-Lung Cancer Study Group.

The Lung Cancer Study Group of the International Society of Chemotherapy (ISC-LCSG) organized multinational, cooperative, prospective and randomized trials for the cure of patients with small cell lung cancer at early stages (T1,2N0M0). Surgery for cure was used first, followed by postoperative chemotherapy, and thereafter by prophylactic cranial irradiation. Eight cycles of standard chemotherapy (CAV-cyclophosphamide-doxorubicin-vincristine) or 6 intermittent cycles of alternating chemotherapy, using 3 different drug combinations, were administered 1-2 weeks postoperatively for 6 months after randomization. A total of 183 evaluable patients received surgery for cure at 23 cooperating hospitals. The preliminary evaluation of ISC-studies I and II per May 1993 resulted in the 30-month total survival of 63% from 68 patients after complete resection at TN0M0R0-stages and 37% from 27 patients after such resections at TN2M0R0-stages. Their incidence of local recurrence as first relapse was quite similar (11/47:8/39). The related 4-year recurrence-free survival (57%, 37%), indicating a plateau-like curve of long-term survivors. These promising results have to be confirmed by larger studies. We conclude that the indication for surgery as the first treatment step for SCLC should be the same as for the other non-small subtypes of lung cancers.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

The impact of surgery on the multidisciplinary treatment of bronchogenic small cell carcinoma (updated review including ongoing studies).

Recent results of studies on patients with SCLC treated by surgery with curative intent followed by adjuvant chemotherapy demonstrate a definite progress in comparison to non-surgical-treatment programs for patients with comparable stage of disease. Of 186 randomized patients enrolled for the multicenter cooperative ISC-Study I and II, 76 patients with stage pT1-3N0M0 received surgery for cure followed by chemotherapy and selective radiotherapy to the brain. The projected 4 year crude survival rate by September 1991 was 57%. In 27 of 43 patients with stage pT1-3N2M0, the tumors were completely resected, resulting in a 4 year survival rate of 32%. The survival curve for both groups of patients shows a sharp bent at 27 months postoperatively, whereafter the survival curves take a plateau-like course. These promising results were confirmed by several other groups. They are in favour of initial surgery for resectable tumors, followed by postoperative chemotherapy, while patients on preoperative chemotherapy followed by adjuvant surgery showed less favourable results.

Adult↗
PubMed1991

Multimodality treatment for small cell bronchial carcinoma. Preliminary results of a prospective, multicenter trial. The ISC-Lung Cancer Study Group.

Preliminary results of the 1984 ISC (International Society of Chemotherapy) lung cancer studies I and II as of June 1990 are based on 146 patients with small cell bronchial carcinoma from 23 departments of thoracic surgery. All patients received surgery for cure in cTNM stages I and II followed by randomization for two different types of chemotherapy. For disease-free patients after completion of postoperative chemotherapy, prophylactic cranial irradiation (PCI) was administered. For the two different chemotherapeutic regimens, no statistically significant differences in survival (SVR) could be observed. Each patient was classified by the pTNM system. There were 63 patients with stage I, 44 patients with stage II and 38 patients with stage III disease. Four years after surgery, 63 patients with N0 disease had a SVR of 50%, 51 patients with N1 disease 31%, and 32 patients with N2 disease, 23%. No prolongation of brain-metastasis-free time for 62 patients receiving PCI was shown. It is concluded that initial surgical resection for small cell lung cancer in stages I and II followed by intensive chemotherapy is an appropriate therapeutic approach.

Adult↗
PubMed1990

The role of chemotherapy including ifosfamide for ovarian carcinoma. Austrian Collab. Ovarian Cancer Study Group.

On the basis of the results of earlier studies, 30 departments of gynecology have been cooperating nationwide in Austria since 1980 to promote the use of adjuvant chemotherapy after surgery for cure of ovarian carcinoma in early stages and the role of lymph node dissection and of second-look operation. Results recorded in more than 160 patients treated with adjuvant chemotherapy after so-called radical surgery performed in disease stages I and II demonstrate that only highly differentiated tumours in stage Ia can be cured by surgery only with no further adjuvant treatment. This underlines the necessity for staging. More than 200 patients with TNM stages III and IV were randomized after debulking surgery to receive treatment with different kinds of drug combinations to compare the therapeutic efficacy of a sequential alternating drug regimen consisting of Adriamycin-cisplatin + vincristine-cyclophosphamide + high-dose methotrexate with that of the combination of Adriamycin-cyclophosphamide and that of Adriamycin-cisplatin. High-dosed ifosfamide was also used in pilot studies.

Cyclophosphamide↗
PubMed1990

The importance of surgery as the first step in multimodality treatment of small cell bronchial carcinoma. The ISC Lung Cancer Study Group.

For patients with small cell lung cancer (SCLC) in their early stages (TNM I, II), surgery for cure was used to eliminate the primary tumour and its regional lymph-nodes followed by intermittent chemotherapy and radiotherapy within the first six postoperative months. After the pathohistological examination of the operation-specimen a two-arm-randomization was performed: standard chemotherapy (1000 mg/m2 cyclophosphamide, 50 mg/m2 doxorubicin, 1.4 mg/m2 vincristine) compared with sequential chemotherapy using three different drug-combinations (A: 1500 mg/m2 cyclophosphamide, 100 mg/m2 lomustine, 15 mg/m2 methotrexate; B: 1000 mg/m2 cyclophosphamide, 40 mg/m2 doxorubicin, 1 mg/m2 vincristine; C: 5 x 1.6 g/m2 ifosfamide plus mesna, 5 x 120 mg/m2 etopside). Thereafter disease-free patients only received prophylactic cranial irradiation (PCI: administering 3600 TD Gy/18 fractions) according to the protocols of the International Society of Chemotherapy Studies I and II. Preliminary evaluations in March 1990 of 170 patients from 24 cooperating departments for thoracic surgery showed that the projected life-table four-year-survival rate of 63 patients with SCLC at pTNM-stage I was 61%, of 54 patients at pTNM-stage II was 35%, of 13 patients at stage pT3, 4 NO, 1 MO was 59% and of 40 patients at stage pT N2 MO was 35%. The indication for surgery is emphasized for pTNM-stages I + II. For N2-lesions surgery would not be recommended in general, but the survival rate seems to indicate that this treatment was not detrimental, being rather more favourable compared with chemotherapy or radiotherapy alone. The continuation and enlargement of these studies seem not only justified, but emphatically indicated.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

The role of ifosfamide and cyclophosphamide in the multi-modality treatment after surgery for cure for small-cell bronchial carcinomas (SCLC).

For the optimisation of the therapy for small cell bronchial carcinomas (SCLC), surgery is used to eliminate the primary tumor and its regional lymph nodes and chemo- and radiotherapy for the general treatment of micrometastasis. After patho-histological examination of the operation specimen, randomization for two arms is performed for a standard chemotherapy (CAV) or a sequential chemotherapy using three different drug combinations. Thereafter all disease-free patients receive prophylactic cranial irradiation (PCI). Preliminary evaluations in December 1987, of 112 patients from 19 cooperating departments show that the survival rate projected for 2 yr of 43 patients at stage pT1-3 N0 M0 is 76%, of 43 patients at stage pT1-3 N1 M0 it is 63% and of 26 patients at stage pT1-3 N2 M0 it is 38%.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Rationale for surgery as the first step in the multimodality treatment of small cell lung cancer (SCLC).

The role of surgery has to be reconsidered in combination with chemo/radiotherapy for patients with SCLC at early stages, determined by the pTNM-staging system. This combined multimodality treatment can be seen as a model-like example for the most effective progress gained during the last 20 years. Surgery followed by chemotherapy is used in ongoing cooperative studies. In other trials, chemotherapy is followed by surgery for responding patients. It seems reasonable to expect that after appropriate observation times the comparison of these ongoing trials would most probably lead to the conclusion that for stage I, II surgery should be the first step followed by chemo- and radiotherapy, whereas for stage III debulking chemotherapy should be given to distinguish responding patients, who may thereafter receive adjuvant surgery.

Carcinoma, Small Cell↗
PubMed1989

The importance of surgical and multimodality treatment for small cell bronchial carcinoma.

In a cooperative international lung cancer multimodality treatment trial, 112 patients with small cell lung cancer underwent initial surgical resection and were then randomized to receive one of two intensive postoperative chemotherapeutic regimens, followed by prophylactic cranial irradiation in the disease-free patients. Regimen A consisted of eight courses of cyclophosphamide, doxorubicin, and vincristine and regimen B of two courses of three sequential drug combinations: (1) cyclophosphamide, lomustine, and methotrexate; (2) cyclophosphamide, doxorubicin, and vincristine; and (3) ifosfamid and etoposide. In 47 patients the diagnosis was known preoperatively and in 65 it was not confirmed until the resected specimen was examined (all diagnoses were reviewed by a referee pathologist). Each patient was classified by the pathologic TNM characteristics. There were 38 patients with stage I disease, 39 patients with stage II, and 35 patients with stage IIIa disease. In stage IIIa there were nine patients with T3 N0-1 disease and 26 with T1-3 N2 disease (most N2 disease was clinically undetected until thoracotomy or was discovered only by routine histologic examination of the resected mediastinal nodes). Early survival rates at 24 months calculated by the life table method are as follows: stage I, 76%; stage II, 56%; and stage IIIa, 49% (T3 N0-1, 89%; T1-3 N2, 35%). Survival rates at 36 months are 62%, 50%, and 41% (74% and 29%), respectively. The projected 36-month survival rate for 43 patients with N0 disease is 65%; for 43 with N1 disease, 52%; and for 26 with N2 disease, 29%. No difference in survival has been noted in either chemotherapy treatment group. It is concluded that initial surgical resection for limited small cell cancer (stage I, II, and T3 N0-1) followed by intensive chemotherapy is an appropriate therapeutic approach. For T1-3 N2 disease the results are inconclusive.

Actuarial Analysis↗
PubMed1988

Surgery for cure followed by combined modality treatment for small cell bronchial carcinoma. ISC Lung Cancer Study Group.

For patients with small cell lung cancer (SCLC) at early stages (TNM I, II) surgery for cure is used to eliminate the primary tumour and its regional lymph-nodes followed by intermittent chemotherapy and radiotherapy within the first six postoperative months. After the pathohistological examination of the operation-specimen a two-arm-randomization is performed: standard chemotherapy compared with sequential chemotherapy using three different drug-combinations. Thereafter tumour-free patients only receive prophylactic cranial irradiation. In preliminary evaluations of March 1988, of 121 patients from 20 cooperating departments it was found that the projected life-table survival rate, three years postoperatively, of 47 patients with SCLC at stages pT1-3 N0 M0 was 65%, of 46 patients at stages pT1-3 N1 M0, 56% and of 28 patients at stages pT1-3 N2 M0, 34%. The indication for surgery were emphasized for pTNM-stages I+II. For N2-lesions surgery would not be recommended in general, but the survival rate seemed to indicate that this treatment was not detrimental, but rather more favourable compared with chemotherapy or radiotherapy only. The continuation and enlargement of these studies seem not only justified but emphatically indicated. Multicentre cooperation has to be organized to collect within a reasonable period of time a sufficient number of patients to enable subdivisions to be made according to various prognostic factors.

Aged↗
PubMed1987

Multimodality treatment with surgery in small-cell lung cancer.

The paper reviews the role of surgery in the local treatment of the primary tumour of small-cell bronchial carcinomas (SCLC) and the preliminary results of a multicentre cooperative prospective randomized trial with multimodality treatments of SCLC. This randomized cooperative trial was activated in 1979 comparing a new sequential intermittent polychemotherapy (sq CT) of three different drug combinations alternatingly given intermittently within one year after surgery, with a standard chemotherapy (CT) of one combination of four drugs given intermittently within three years after surgery. Observations on 25 patients at nine different cooperating surgical departments showed that sq CT was applicable and unexpected side-effects did not occur. Live table curves, calculated from 56 patients up to February 1986, indicate the improvement of the survival rate five years after surgery for the cure of 25 patients receiving sq CT after surgery in comparison with 31 patients receiving standard chemotherapy (36% : 22%). Following discussions of this and other results at the symposium "Adjuvant Therapy of Small-Cell Bronchial Carcinoma" at the 13th Congress of the International Society of Chemotherapy (ISC) 1983 in Vienna, a related new protocol was designed and activated by a further enlarged ISC-Study-Group in October 1984. This protocol for a two-armed randomized cooperative trial for patients operated for T1, 2N0M0SCLC is comparing a chemotherapy-combination 1 (CAV)--as also used in a trial of the North American Lung Cancer Study Group-0--with chemotherapy 2 (sq CT) as used in our forementioned previous study.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Combination of surgery and chemotherapy for small-cell bronchial carcinoma.

In several test model systems using spontaneous metastasizing experimental tumours, convincing data indicate the importance of the tumour burden left after surgery for the efficacy of the combination of surgery and chemotherapy. Early removal of the primary tumour by radical surgery for cure seems to improve the conditions for chemotherapy. Since 1979, in nine different departments of thoracic surgery, patients with small-cell carcinoma of the lung (SCCL) have been randomized after surgery for cure to receive a new sequential intermittent polychemotherapy (sq.CT) of 3 different alternating drug combinations given intermittently over 1 year, or one 4-drug combination chemotherapy (CT) given intermittently over 3 years. The calculation of their life table curves at 1 August 1984 indicated an improvement in the 4-year survival rate of 23 patients receiving sq.CT to about 50%, compared with a survival rate of about 30% for 29 patients receiving CT. The number of patients is still too small for firm conclusions to be drawn, but it is concluded that surgery for SCCL seems to be an advisable measure for the efficacy of aggressive intermittent long-term polychemotherapy. However, this can only be proved in large cooperative studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

The angioarchitecture of the Lewis lung carcinoma in laboratory mice (a light microscopic and scanning electron microscopic study).

53 Lewis lung carcinomas implanted subcutaneously into C57BL/6-mice were examined. The animals were killed at various stages of tumor growth (TG) and prepared for histology and for scanning electron microscopy (critical-point-dried tissue; vascular corrosion casts). Prior to casting animals were rinsed using different perfusion pressures. Casting was done by manual injection of the resin, whereby different influx-rates were applied resulting in low, medium and high pressure preparations. We discern 3 phases of tumor angiogenesis (TA) occurring during 4 stages of TG among which vasodilation establishes the first reaction of the host vascular system to a growing tumor implant. During this stage 1 of TG, tumor nidation, nearby sinusoidal dilated host capillaries form globular outgrowings (phase 1 of TA). Subsequently radially arranged sprouts, which preferentially arise from venous host vessels, grow into the centre of the implant (phase 2 of TA). Stage 2 of TG, early tumor growth, is characterized by necrosis of the central tumor tissue and the development of a central avascular cavity. Thus the tumor vascular system is organized like a hollow sphere with a central cavity and a peripheral vascular "envelope" with large vessels embracing the tumor and centrifugally growing vascular sprouts, which arise from the venous part of the vascular "envelope" and invade the surrounding host tissue (phase 3 of TA). During stage 3 of TG, late tumor growth, many vessels of the basket-like vascular "envelope" obliterate. In stage 4 of TG, prefinal phase, the peripheral vascular density decreases continuously. Thus vascular sprouting and proliferation of viable tumor cells is confined to basal regions of the tumor.

Arterioles↗
PubMed1986

The characteristic structural features of the blood vessels of the Lewis lung carcinoma (a light microscopic and scanning electron microscopic study).

Vascular corrosion casts of Lewis lung carcinomas (LLC) grown subcutaneously in C57BL/6-mice are correlated with histological sections and with tumor tissue prepared for scanning electron microscopy (SEM). By making low, medium and high pressure cast preparations we studied the influence of perfusion and injection pressure on the resulting cast sample. Three types of vascular proliferations are distinguishable in LLC: Small globular outgrowths on sinusoidal dilated tumor capillaries, caused by proliferation of their endothelial cells. New sprouts on surrounding host vessels, invading the small, still avascular implant. Superficially located, centrifugally running sprouts in peripheral regions of large tumors. They invade the surrounding host tissue. Vascular sprouts are of venous origin, have a fragmentary endothelium and are rather "leaky" if casted. High pressure preparations of large tumors reveal central avascular cavities surrounded by centripetally running, compressed and blind ending tumor vessels. Irrespective of the applied injection pressure, the casts always exhibit extravasal channels caused by degeneration of the endothelium of central tumor vessels. We show that SEM of vascular corrosion casts combined with histology not only demonstrates such contrary processes as the development of tumor blood vessels and the simultaneously occurring vascular degeneration, but also elucidates all other morphological characteristics of the tumor vascular system.

Animals↗