Rudolf Morant - Academia.edu (original) (raw)
Papers by Rudolf Morant
Annals of Oncology, May 1, 1998
Purpose: A wide variety of fiuorouracil (FU)-plus-leucovorin (LV) dose schedules are in clinical ... more Purpose: A wide variety of fiuorouracil (FU)-plus-leucovorin (LV) dose schedules are in clinical use for the treatment of advanced colorectal cancer. Only the monthly low-dose LVplus-FU regimen, as used by the North Central Cancer Treatment Group, has demonstrated a lasting survival benefit as opposed to FU alone (J Clin Oncol 1989; 7: 1407-1417). The Swiss Cancer Group adopted this regimen for a confirmatory phase III trial but used the same dose-intensity of fiuorouracil in both treatment arms. Patients and methods: Patients with inoperable or metastatic colorectal cancer were randomized to receive monthly FU 400 mg/m 2 /day plus LV 20 mg/m 2 /day as intravenous push daily for five days, or FU alone. Results: Three hundred nine of the 310 patients randomized were eligible and included in the analysis. The objective response rate for patients with measurable disease was 9% with FU alone and 22% with FU-plus-LV (P = 0.0001). The median progression-free survival was 3.9 versus 6.2 months (P = 0.003) and the overall survival 10 versus 12.4 months (P = 0.02). The major prognostic factors for survival were performance status, weight loss, and disease symptoms. WHO > 2 toxicity, consisting of stomatitis (P = 0.001), diarrhea (P-0.001), and nausea (P = 0.001), was more pronounced for FU-plus-LV, without fatal events. Conclusions: This is the largest published randomized trial to compare FU-plus-LV to FU alone in advanced colorectal cancer. It confirms the survival benefit obtained from biomodulating monthly FU with low-dose LV. The toxic effects of FU-plus-LV were acceptable to most patients, and they responded well to FU dose reductions. In the absence of an ideal dose-intense FU monotherapy regimen, monthly FU with lowdose LV provides a simple and economical means by which to achieve adequate FU efficacy in the treatment of advanced colorectal cancer.
Bulletin des médecins suisses, Apr 21, 2021
Die Geschichte der Krebsliga Ostschweiz zeigt, welch grosse Wirkung der Einsatz Einzelner für die... more Die Geschichte der Krebsliga Ostschweiz zeigt, welch grosse Wirkung der Einsatz Einzelner für die Interessen von Krebsbetroffenen entfalten konnte: So betrieb die Krebsliga eines der ersten zytologischen Labors, gründete das erste Krebsregister der Schweiz, gab den Anstoss zu einer onkologischen Abteilung am Kantonsspital St. Gallen und förderte dann deren Weiterentwicklung massgeblich. 65 Jahre Krebsliga Ostschweiz Anlässlich des 65. Geburtstags der Krebsliga Ost schweiz hat der Historiker Théo Buff die vorhandenen Unterlagen zusammengetragen, gesichtet und im Kon text soweit möglich verifiziert. Am Anfang der spannenden Geschichte, die zutage ge fördert wurde, stehen Individuen und Visionäre mit ei ner kleinen Wohltätigkeitsorganisation. Diese hat sich über die Jahrzehnte zur heutigen stabilen und professi onell geführten Institution entwickelt mit vielfältigen Aufgaben in der Betreuung von Krebsbetroffenen und deren Angehörigen in allen Krankheitsphasen, in der Krebsregistrierung und Vorsorge von Krebserkran kungen. Diese insgesamt erfreuliche Entwicklung ver lief nicht gradlinig, sondern war zeitweilig durch harte Richtungskämpfe, Zank und Enttäuschungen geprägt. In diesem Artikel beschränken wir uns auf einen Aspek t, der sich bei der Sichtung der Unterlagen als wichti ge, für manche auch überraschende Erkenntnis herauskristallisiert hat: Die lokale Krebsliga war mass geblich an der Entstehung und Entwicklung der Onko WEITERE ORGANISATIONEN UND INSTITUTIONEN Krebsliga Ostschweiz 539
Oncology Research and Treatment, 2002
Chemotherapy with paclitaxel and carboplatin 3-weekly is active in many tumors. Major toxicities ... more Chemotherapy with paclitaxel and carboplatin 3-weekly is active in many tumors. Major toxicities are myelosuppression and neurotoxicity. Weekly administration of taxanes allows high dose intensity with reduced toxicity. 131 patients with solid tumors were treated as outpatients with paclitaxel 75 mg/m(2) and carboplatin AUC 2-3 days 1, 8, 15 every 4 weeks irrespective of pretreatment and partly in neoadjuvant and multimodal concepts. 125 patients (median age 58 years) were evaluable for response and toxicity, of whom 45 suffered esophageal carcinoma (19 patients in neoadjuvant treatment) and 31 non-small cell lung cancer. 49 patients were pretreated. 23 patients received concomitant radiotherapy of esophagus or lung in doses ranging from 40 to 60 Gy. We observed a low hematologic toxicity with 15.2% grade-III/IV leukopenia/granulocytopenia and 3.2% thrombocytopenia grade III/IV. Neurotoxicity grade II was reported in 14 patients. Main toxicity with radiotherapy was esophagitis grade II or III in 7 out of 23 patients. Overall response rate was 54.2%. 5 out of 19 patients treated neoadjuvantly for esophageal cancer reached a pathological complete response. Weekly paclitaxel and carboplatin is safe and feasible in outpatients and a high dose intensity can be achieved. The favorable toxicity profile allows treatment of elderly and pretreated patients. Response rate is high including pathological complete responses and responses appear quickly, making this therapy most suitable for multimodal and neoadjuvant treatments.
Annals of Oncology, Sep 1, 2008
strategic planes of cancer prevention Cancer prevention-clearly less developed in Continental Eur... more strategic planes of cancer prevention Cancer prevention-clearly less developed in Continental Europe than cancer therapy-can be delivered on three planes, as defined below, in an inverse sequence according to their present clinical importance [1]. tertiary cancer prevention Usually defined as the prevention of locoregional relapse and/or metastatic disease after, hopefully curative, primary local treatment by surgery or radiotherapy. Tertiary prevention therefore embraces the expanding and important field of adjuvant therapy (chemo-and radiotherapy, antiendocrine treatments, targeted treatments), prolonging disease-free intervals and even leading to significant survival gains in several neoplastic diseases such as testicular cancers, malignant lymphomas, breast and colon cancer and others. secondary cancer prevention Defined as aiming at detection of certain cancer types at a very early, hopefully not yet metastatic, stage leading to lesser extent of therapy and to higher cure rates. Secondary prevention (actually a misnomer) is performed and only effective on a population basis (screening programs) in given population segments at risk, e.g. secondary prevention of breast cancer by mammography screening for women between 50 and 70 years of age. primary cancer prevention The aim of primary prevention is to reduce the incidence of cancer by controlling (or avoiding) exposure to known risk factors, by increasing an individual's resistance (immunization, vaccination) or by interfering with the early carcinogenic process in risk individuals (chemo-or endocrine prevention). This is clearly the 'youngest' type of cancer prevention and still in the early phases of gaining clinical recognition and acceptance. Primary, especially chemo-prevention, in two major genderassociated cancer types (breast and prostate cancer) will be the main topic in this paper.
The Breast, Mar 1, 2009
Goals: Treatment decision at time of breast cancer recurrences is usually based on the hormones r... more Goals: Treatment decision at time of breast cancer recurrences is usually based on the hormones receptors and HER2 status of the primary breast cancer. Our goal was to verify the assumption that the tumor biology doesn't change during progression. Methods: In the STB (Tumorbank Basel Foundation) we have investigated the status of these three predictors in 124 paired primary and recurrent tissue samples. The recurrences included 81 local regional relapse and 43 metastatic diseases of the chest, skin or bones. The median time to recurrence was 26 months. Patients with positive hormone receptors status received tamoxifen alone as adjuvant treatment. We evaluated the results investigating changes of the absolute quantitative protein levels of the three receptors and of the status as clinical predictors for therapy choice. Results: In general, we observed no statistical significant changes between the protein expression levels in the recurrence tissues as compared to the respective primary specimens. However, out of the 96 patients with a negative HER2 status at the time of the primary tumor 7 displayed a positive HER2 status at recurrences (4 loco regional and 3 distant metastatic events). In 5 patients this event was accompanied by significantly lower levels of PgR and/or ER. This observation is rather important since it explains why same patients with HER2 negative status could profit of a first line Herceptin ® therapy. In addition, it is also relevant to notice that 7 patients with a HER2 positive status in the primary tumor were found to have HER2 negative loco regional (n = 3) or distant metastatic (n = 4) diseases. Conclusion: Monitoring of predictors at recurrences is important as well as investigation of causative agents. 0071 The 70-gene MammaPrint profile allows to identify a subgroup of very good-prognostic patients with primary breast cancer and 4−9 positive lymph nodes
PubMed, Oct 11, 1986
Ten patients with acute myeloid leukemia were treated with a high-dose ara-c regimen (3 g twice d... more Ten patients with acute myeloid leukemia were treated with a high-dose ara-c regimen (3 g twice daily for 6 days). 5 patients (50%) achieved a complete remission lasting for a median duration of 5 months. These patients had all achieved a complete remission following standard treatment with ara-c. High-dose ara-c was ineffective in 2 patients resistant to standard ara-c protocols. The most important side effects of high-dose ara-c were conjunctivitis and cerebellar symptomatology. In one case a severe diffuse encephalopathy with cerebellar predominance set in at a remarkably late stage (45 days after starting treatment). Our results and those of other authors suggest that treatment with high-dose ara-c should be used with caution.
PubMed, Nov 5, 1994
CYFRA 21-1 (CYFRA) is a new tumor-associated marker which appears to be useful in monitoring non-... more CYFRA 21-1 (CYFRA) is a new tumor-associated marker which appears to be useful in monitoring non-small cell bronchial carcinoma. We examined 193 sera from tumor patients (92 of whom had bronchial carcinoma), and 62 patients with benign lung disease. Sensitivity and specificity of CYFRA was compared with that of CEA, TPA, TPS and SCC in squamous cell bronchial carcinoma and with that of NSE in small cell bronchial carcinoma. The sensitivity of CYFRA in other tumor localizations was also assessed. In squamous cell bronchial carcinoma CYFRA proved to be the best marker with respect to sensitivity (58%) and specificity (98%). In gastrointestinal tumors CYFRA had a similar sensitivity to CEA. Since the two markers do not correlate their sensitivity is additive. In conclusion, CYFRA is confirmed as marker of first choice in squamous cell bronchial carcinoma. In other tumors CYFRA displayed a similar sensitivity to CEA.
![Research paper thumbnail of [Osteopenia in beta-thalassemia major]](https://attachments.academia-assets.com/115622030/thumbnails/1.jpg)
](PubMed, Nov 2, 1996
Regular blood transfusions in patients with beta-thalassaemia major lead to secondary hemochromat... more Regular blood transfusions in patients with beta-thalassaemia major lead to secondary hemochromatosis in the majority of cases. As a consequence of chronic iron overload, many endocrinopathies may occur. The most frequent endocrine dysfunction is hypogonadotropic hypogonadism, which is mainly responsible for osteopenia in as much as 80% of thalassemic patients. The frequencies of other endocrine disorders (hypothyroidism, diabetes mellitus and hypoparathyroidism) are lower. We investigated 5 female patients aged 22-25 years for endocrine dysfunction and bone density. All presented with hypogonadotropic hypogonadism and amenorrhea (four primary and one secondary). 4 patients showed absent or delayed pubertal development and short stature (below 10th percentile). In all five, hypogonadism is the most relevant cause of osteopenia as demonstrated by osteodensitometry. Endocrine disorders, especially absent pubertal development, should be detected in good time and treated with hormonal replacement. Established osteopenia is treated hormonally and with vitamin D3 and calcium.
Supportive Care in Cancer, 1994
In a prospective dose-escalation study tolerability and effectiveness of repeated infusions with ... more In a prospective dose-escalation study tolerability and effectiveness of repeated infusions with intravenous pamidronate were investigated. A total of 80 patients with proven malignancy and pain due to osteolytic bone disease were enrolled. Doses of 30 mg, 45 mg, 60 mg and 90 mg pamidronate, given every 4 weeks, 3 weeks or 2 weeks were tested. Thus dose intensity was increased by giving higher doses and/or by shortening the intervals. A combined palliation score on the bases of pain score (WHO), analgesic score (WHO) and improvement of performance status (SAKK/ECOG) was rated by the physician on a six-point scale. Regression analysis showed a close correlation between dose intensity and effect (Pearson's R = 0.7: P < 0.0001). A statistically significantly different palliative score for patients treated with low (below 15 mg/week), medium (16-30 mg/week) and high doses (above 31 mg/week) of pamidronate was found (P= < 0.01). A dose intensity below 10 mg pamidronate/ week and single doses of 30 mg had no clinically relevant benefit, whereas dose intensities of 25-45 mg/week showed a significant palliative effect. We conclude that pamidronate should be given in a close intensity of 20 mg per week or more in patients with far advanced osteolytic bone disease. Best results are obtained with high doses of 60 mg or 90 mg pamidronate. Further investigations by prospective randomized trials are needed to determine the optimal dose and schedule of pamidronate infusions.
European Journal of Haematology, Apr 24, 2009
A 65‐year‐old woman with B‐cell chronic lymphocytic leukemia (CLL) and pure red cell aplasia (PRC... more A 65‐year‐old woman with B‐cell chronic lymphocytic leukemia (CLL) and pure red cell aplasia (PRCA) is described. After initial chemotherapy with three different regimens over 3 months (prednisone, chlorambucil/vincristine, cyclophosphamide, bleomycin/cyclophosphamide, etoposide, prednisone), normalization of the blood lymphocyte count was observed, but lymphocyte infiltration of the bone marrow persisted and erythropoiesis remained virtually absent. Monotherapy with cyclosporin‐A (CyA) was begun. After 35 days, a marked increase in the reticulocyte count was observed, and with continuing therapy, there was a rapid increase in the hemoglobin level. Follow‐up after 13 months of uninterrupted treatment with CyA revealed remission of both CLL and PRCA. CyA should be investigated further as a therapeutic modality for PRCA in patients with CLL, and such trials might provide further clues to the pathogenesis of this peculiar association.
Annals of Oncology, Feb 1, 2000
Background: GI147211, a 10,11-ethylenedioxy substituted analogue of camptothecin (CPT), was broug... more Background: GI147211, a 10,11-ethylenedioxy substituted analogue of camptothecin (CPT), was brought into clinical development because of its higher water solubility and greater potency as compared to topotecan (TPT). The antitumor activity of GI147211 as second-line therapy in small-cell lung cancer (SCLC) was assessed after stratification of patients in refractory (no response to initial treatment or relapse within three months from last cycle) and chemosensitive (relapse more than three months from last cycle). Patients and methods: Sixty-seven patients were entered in the study and sixty-two were evaluable for response, twentyeight in the refractory and thirty-four in the chemosensitive group. All patients had received 1 line of chemotherapy; radiation had also been given in 29 cases, 6 in the refractory and 23 in the chemosensitive group. GI147211 was administered at 1.2 mg/m 2 /day as 30-min infusion for five consecutive days every three weeks. Results-The overall response rate was 16.6% (11 of 66 patients; 95% confidence interval (95% CI): 8.5%-27.5%), 10.3% (3 of 29 patients; 95% CI: 2.2%-27%) in the refractory and 21.1% (8 of 37 patients; 95% CI: 9.5%-37%) in the chemosensitive group. Only partial responses (PR) were observed with a median duration of PR of 4.8 months (5.7 months in the refractory and 5.2 in the chemosensitive group). Hematological toxicity consisted mainly of neutropenia (grades 3-4 in 25% of cycles) and thrombocytopenia (grades 3-4 in 23% of cycles); non-hematological toxicity was mild to moderate and consisted of nausea (22% of cycles), vomiting (11%), malaise (34%). Conclusions: At the dose and schedule tested GI147211 is an active new agent for second-line treatment of SCLC; the antitumor activity and toxicity profile are comparable to those observed with TPT which remains the leading CPT analogue for salvage treatment. Interest has been renewed in the clinical development of GI147211 by preclinical data with the liposomal formulation showing an increased therapeutic index.
Digestion, 1996
In an open phase III study, octastatin was given as a continuous subcutaneous (s.c.) infusion to ... more In an open phase III study, octastatin was given as a continuous subcutaneous (s.c.) infusion to 35 patients (mean age 62 years) with malignant neuroendocrine gastro-intestinal tumours and the carcinoid syndrome. The wash-out was often incomplete because of the advanced stage of disease. The starting dose of 1.5 mg/24 h was increased up to 3.0 mg/24 h at 3 months in some patients. The carcinoid syndrome disappeared in 20% of patients at 3 months and in 23% at 6 months, with 43 and 45% of patients, respectively, experiencing an improvement. The mean Karnovsky index increased by > 10% in 40% of patients at 3 and 6 months. Urinary 5-hydroxyindoleacetic acid (U-5-HIAA) levels at 3 months normalised in 1 patient, fell in 20% (by > 50%; p = 0.0021) and stabilised in 66%. The respective values at 6 months were 1, 17% (p = 0.023) and 60%. There was also a significant decrease in plasma chromogranin levels at 3 months (p = 0.042), which did not persist at 6 months. Tumour size fell (by > 50%) in 1 patient by 6 months but this patient had undergone chemoembolisation one month prior to the start of the study. Most patients had tumour size stabilisation (76 and 68%) or progression (20 and 24%) at 3 and 6 months, respectively. Dose escalation from 1.5 to 3.0 mg did not significantly improve clinical, biochemical or tumour responses. The treatment was well tolerated with minor adverse events. In an open pilot phase II study of 19 patients (mean age 58 years), patients were given high dose somatuline with a maintenance dose of 12,000 mg/day in 4 divided s.c. injections. U-5-HIAA, which was elevated in 13 patients with a mean of 444 mumol/day before the start, was reduced to 58% of baseline at 3 months, 68% at 6 months (p = 0.04), 66% at 9 months and 75% at 12 months (p = 0.14). P-chromogranin was elevated in 18 patients, with a mean of 5,300 micrograms/l before the start, and was reduced to 52, 55, 63 and 64% of the baseline at 3, 6 (p = 0.039), 9 and 12 (p = 0.013) months, respectively. In the responding patients, apoptosis was induced.
Urologia Internationalis, Jun 6, 2015
verse events were nausea and vomiting. Conclusion: Gefitinib in combination with chemotherapy did... more verse events were nausea and vomiting. Conclusion: Gefitinib in combination with chemotherapy did not improve efficacy in advanced urothelial cancer.
Annals of Oncology, May 1, 1995
Interferon (IFN) treatment trials in multiple myeloma have yielded discordant results regarding r... more Interferon (IFN) treatment trials in multiple myeloma have yielded discordant results regarding response rates, maintenance duration, and survival times. Further randomized trials and global evaluations of available data are urgently needed for clarification. 256 patients participated in a randomized trial, 125 on IFN + VMCP, and 131 on VMCP alone. 100 patients were randomized to IFN maintenance (n = 46) or were untreated controls (n = 54). Global evaluations are based on 1,518 patients in induction and 924 in maintenance trials. The induction trial demonstrated a significantly (p < 0.05) lower rate of progressive disease under IFN + VMCP (10.6%) than under VMCP (22.9%), but this benefit was limited to stage I or II patients. Median progression-free survival was longer in the IFN + VMCP arm (23.2 months vs. 15.8 months); median overall survival did not differ significantly (38.9 vs. 30.2 months). The IFN maintenance treatment trial showed significantly superior results in the IFN arm versus controls (median maintenance duration: 17.8 months and 8.2 months (p < 0.01), survival: 50.6 and 34.4 months (p < 0.05), respectively). Previous IFN treatment increased the benefits of IFN maintenance therapy. Adverse effects of IFN during induction were hematologic toxicity, fever, and infections, requiring dose reductions. Toxic effects of IFN maintenance treatment were mild. Global evaluations of randomized trials showed small but significant benefits of combined IFN induction therapy and significantly prolonged maintenance duration and survival under IFN maintenance. Presently available data support the use of IFN maintenance treatment because it significantly prolongs maintenance duration and survival. IFN added to induction chemotherapy resulted in minor improvements at the expense of increased toxicity, highlighting the need for better induction regimens.
Journal of Clinical Oncology, Apr 1, 2002
To determine the efficacy and tolerability of combining oxaliplatin with capecitabine in the trea... more To determine the efficacy and tolerability of combining oxaliplatin with capecitabine in the treatment of advanced nonpretreated and pretreated colorectal cancer. Forty-three nonpretreated patients and 26 patients who had experienced one fluoropyrimidine-containing regimen for advanced colorectal cancer were treated with oxaliplatin 130 mg/m(2) on day 1 and capecitabine 1,250 mg/m(2) bid on days 1 to 14 every 3 weeks. Patients with good performance status (World Health Organization grade 0 to 1) were accrued onto two nonrandomized parallel arms of a phase II study. The objective response rate was 49% (95% confidence interval [CI], 33% to 65%) for nonpretreated and 15% (95% CI, 4% to 35%) for pretreated patients. The main toxicity of this combination was diarrhea, which occurred at grade 3 or 4 in 35% of the nonpretreated and 50% of the pretreated patients. Grade 3 or 4 sensory neuropathy, including laryngopharyngeal dysesthesia, occurred in 16% of patients on both cohorts. Capecitabine dose reductions were necessary in 26% of the nonpretreated and 45% of the pretreated patients in the second treatment cycle. The median overall survival was 17.1 months and 11.5 months, respectively. Combining capecitabine and oxaliplatin yields promising activity in advanced colorectal cancer. The main toxicity is diarrhea, which is manageable with appropriate dose reductions. On the basis of our toxicity experience, we recommend use of capecitabine in combination with oxaliplatin 130 mg/m(2) at an initial dose of 1,250 mg/m(2) bid in nonpretreated patients and at a dose of 1,000 mg/m(2) bid in pretreated patients.
Oncology Research and Treatment, 2003
The insulin-like growth factor (IGF) system performs multiple functions in normal tissue. IGFs ar... more The insulin-like growth factor (IGF) system performs multiple functions in normal tissue. IGFs are involved in normal mammary gland development, but have also been implicated in the pathogenesis of breast cancer. Epidemiological studies found an association between elevated serum levels of IGF-I and an increased risk for breast cancer. IGF-I is the major mediator of growth hormone (GH) action. On the cellular level, IGF-I has a strong influence on cell proliferation and it is a potent inhibitor of apoptosis. Further, IGFs are also involved in angiogenesis. These characteristics are the basis for their involvement in maintenance and progression of cancer. The functions of IGF-I are mainly mediated through the type-I IGF-receptor (IGF-IR). The availability of free IGF-I for interaction with IGF-IR is modulated by IGF binding proteins (IGFBP 1-6). Based on interactions with other receptors, including estrogen and epidermal growth factor receptors, combined targeted therapies may improve breast cancer treatment.
Journal of Clinical Oncology, May 20, 2008
22170 Background: Preliminary reports indicate that dutasteride can suppress progesterone transfo... more 22170 Background: Preliminary reports indicate that dutasteride can suppress progesterone transformation into 5-alpha pregnane by SRD5A1 in breast cancer, resulting in suppression of cell proliferation and detachment. The aim of this study was to investigate SRD5A1 expression according to the breast cancer subtypes and patient characteristics. Methods: SRD5A1 mRNA expression levels were investigated in three breast cancer data sets consisting of a 64 genes Qrt-PCR data set (STB, 168 patients) and two micro-arrays data sets (295 and 286 patients). Results: SRD5A1 mRNA expression was found to be significantly higher in estrogen receptor (ER) negative tumors including the Basal like and HER2-positive subtypes. Moreover, elevated SRD5A1 were found to be associated with pre-menopausal status of the patients, high tumor grade and poor clinical outcome. Conclusions: SRD5A1 mRNA expression was found to be associated with ER-negative breast cancer phenotypes mainly found in tumors obtained from pre-menopausal wome...
Oncology Research and Treatment, 1993
operation while preserving functioning lung tissue. Discussed in this article are sleeve lobectom... more operation while preserving functioning lung tissue. Discussed in this article are sleeve lobectomy, an alternative to pneumoaectomy in patients with cancer in a lobar orifice; segmemectomy or wedge resection. an alternative to lobectomy in those with a peripheral lung cancer: and thoracoscopy, an alternative to open thoracotomy for various chest malignancies. Chemotherapy FOM: An etkctive, non-ciaplatin-baaed combination chemotherapy for advanced non-smukell lung cancer with low toxicity
Annals of Oncology, May 1, 1998
Purpose: A wide variety of fiuorouracil (FU)-plus-leucovorin (LV) dose schedules are in clinical ... more Purpose: A wide variety of fiuorouracil (FU)-plus-leucovorin (LV) dose schedules are in clinical use for the treatment of advanced colorectal cancer. Only the monthly low-dose LVplus-FU regimen, as used by the North Central Cancer Treatment Group, has demonstrated a lasting survival benefit as opposed to FU alone (J Clin Oncol 1989; 7: 1407-1417). The Swiss Cancer Group adopted this regimen for a confirmatory phase III trial but used the same dose-intensity of fiuorouracil in both treatment arms. Patients and methods: Patients with inoperable or metastatic colorectal cancer were randomized to receive monthly FU 400 mg/m 2 /day plus LV 20 mg/m 2 /day as intravenous push daily for five days, or FU alone. Results: Three hundred nine of the 310 patients randomized were eligible and included in the analysis. The objective response rate for patients with measurable disease was 9% with FU alone and 22% with FU-plus-LV (P = 0.0001). The median progression-free survival was 3.9 versus 6.2 months (P = 0.003) and the overall survival 10 versus 12.4 months (P = 0.02). The major prognostic factors for survival were performance status, weight loss, and disease symptoms. WHO > 2 toxicity, consisting of stomatitis (P = 0.001), diarrhea (P-0.001), and nausea (P = 0.001), was more pronounced for FU-plus-LV, without fatal events. Conclusions: This is the largest published randomized trial to compare FU-plus-LV to FU alone in advanced colorectal cancer. It confirms the survival benefit obtained from biomodulating monthly FU with low-dose LV. The toxic effects of FU-plus-LV were acceptable to most patients, and they responded well to FU dose reductions. In the absence of an ideal dose-intense FU monotherapy regimen, monthly FU with lowdose LV provides a simple and economical means by which to achieve adequate FU efficacy in the treatment of advanced colorectal cancer.
Bulletin des médecins suisses, Apr 21, 2021
Die Geschichte der Krebsliga Ostschweiz zeigt, welch grosse Wirkung der Einsatz Einzelner für die... more Die Geschichte der Krebsliga Ostschweiz zeigt, welch grosse Wirkung der Einsatz Einzelner für die Interessen von Krebsbetroffenen entfalten konnte: So betrieb die Krebsliga eines der ersten zytologischen Labors, gründete das erste Krebsregister der Schweiz, gab den Anstoss zu einer onkologischen Abteilung am Kantonsspital St. Gallen und förderte dann deren Weiterentwicklung massgeblich. 65 Jahre Krebsliga Ostschweiz Anlässlich des 65. Geburtstags der Krebsliga Ost schweiz hat der Historiker Théo Buff die vorhandenen Unterlagen zusammengetragen, gesichtet und im Kon text soweit möglich verifiziert. Am Anfang der spannenden Geschichte, die zutage ge fördert wurde, stehen Individuen und Visionäre mit ei ner kleinen Wohltätigkeitsorganisation. Diese hat sich über die Jahrzehnte zur heutigen stabilen und professi onell geführten Institution entwickelt mit vielfältigen Aufgaben in der Betreuung von Krebsbetroffenen und deren Angehörigen in allen Krankheitsphasen, in der Krebsregistrierung und Vorsorge von Krebserkran kungen. Diese insgesamt erfreuliche Entwicklung ver lief nicht gradlinig, sondern war zeitweilig durch harte Richtungskämpfe, Zank und Enttäuschungen geprägt. In diesem Artikel beschränken wir uns auf einen Aspek t, der sich bei der Sichtung der Unterlagen als wichti ge, für manche auch überraschende Erkenntnis herauskristallisiert hat: Die lokale Krebsliga war mass geblich an der Entstehung und Entwicklung der Onko WEITERE ORGANISATIONEN UND INSTITUTIONEN Krebsliga Ostschweiz 539
Oncology Research and Treatment, 2002
Chemotherapy with paclitaxel and carboplatin 3-weekly is active in many tumors. Major toxicities ... more Chemotherapy with paclitaxel and carboplatin 3-weekly is active in many tumors. Major toxicities are myelosuppression and neurotoxicity. Weekly administration of taxanes allows high dose intensity with reduced toxicity. 131 patients with solid tumors were treated as outpatients with paclitaxel 75 mg/m(2) and carboplatin AUC 2-3 days 1, 8, 15 every 4 weeks irrespective of pretreatment and partly in neoadjuvant and multimodal concepts. 125 patients (median age 58 years) were evaluable for response and toxicity, of whom 45 suffered esophageal carcinoma (19 patients in neoadjuvant treatment) and 31 non-small cell lung cancer. 49 patients were pretreated. 23 patients received concomitant radiotherapy of esophagus or lung in doses ranging from 40 to 60 Gy. We observed a low hematologic toxicity with 15.2% grade-III/IV leukopenia/granulocytopenia and 3.2% thrombocytopenia grade III/IV. Neurotoxicity grade II was reported in 14 patients. Main toxicity with radiotherapy was esophagitis grade II or III in 7 out of 23 patients. Overall response rate was 54.2%. 5 out of 19 patients treated neoadjuvantly for esophageal cancer reached a pathological complete response. Weekly paclitaxel and carboplatin is safe and feasible in outpatients and a high dose intensity can be achieved. The favorable toxicity profile allows treatment of elderly and pretreated patients. Response rate is high including pathological complete responses and responses appear quickly, making this therapy most suitable for multimodal and neoadjuvant treatments.
Annals of Oncology, Sep 1, 2008
strategic planes of cancer prevention Cancer prevention-clearly less developed in Continental Eur... more strategic planes of cancer prevention Cancer prevention-clearly less developed in Continental Europe than cancer therapy-can be delivered on three planes, as defined below, in an inverse sequence according to their present clinical importance [1]. tertiary cancer prevention Usually defined as the prevention of locoregional relapse and/or metastatic disease after, hopefully curative, primary local treatment by surgery or radiotherapy. Tertiary prevention therefore embraces the expanding and important field of adjuvant therapy (chemo-and radiotherapy, antiendocrine treatments, targeted treatments), prolonging disease-free intervals and even leading to significant survival gains in several neoplastic diseases such as testicular cancers, malignant lymphomas, breast and colon cancer and others. secondary cancer prevention Defined as aiming at detection of certain cancer types at a very early, hopefully not yet metastatic, stage leading to lesser extent of therapy and to higher cure rates. Secondary prevention (actually a misnomer) is performed and only effective on a population basis (screening programs) in given population segments at risk, e.g. secondary prevention of breast cancer by mammography screening for women between 50 and 70 years of age. primary cancer prevention The aim of primary prevention is to reduce the incidence of cancer by controlling (or avoiding) exposure to known risk factors, by increasing an individual's resistance (immunization, vaccination) or by interfering with the early carcinogenic process in risk individuals (chemo-or endocrine prevention). This is clearly the 'youngest' type of cancer prevention and still in the early phases of gaining clinical recognition and acceptance. Primary, especially chemo-prevention, in two major genderassociated cancer types (breast and prostate cancer) will be the main topic in this paper.
The Breast, Mar 1, 2009
Goals: Treatment decision at time of breast cancer recurrences is usually based on the hormones r... more Goals: Treatment decision at time of breast cancer recurrences is usually based on the hormones receptors and HER2 status of the primary breast cancer. Our goal was to verify the assumption that the tumor biology doesn't change during progression. Methods: In the STB (Tumorbank Basel Foundation) we have investigated the status of these three predictors in 124 paired primary and recurrent tissue samples. The recurrences included 81 local regional relapse and 43 metastatic diseases of the chest, skin or bones. The median time to recurrence was 26 months. Patients with positive hormone receptors status received tamoxifen alone as adjuvant treatment. We evaluated the results investigating changes of the absolute quantitative protein levels of the three receptors and of the status as clinical predictors for therapy choice. Results: In general, we observed no statistical significant changes between the protein expression levels in the recurrence tissues as compared to the respective primary specimens. However, out of the 96 patients with a negative HER2 status at the time of the primary tumor 7 displayed a positive HER2 status at recurrences (4 loco regional and 3 distant metastatic events). In 5 patients this event was accompanied by significantly lower levels of PgR and/or ER. This observation is rather important since it explains why same patients with HER2 negative status could profit of a first line Herceptin ® therapy. In addition, it is also relevant to notice that 7 patients with a HER2 positive status in the primary tumor were found to have HER2 negative loco regional (n = 3) or distant metastatic (n = 4) diseases. Conclusion: Monitoring of predictors at recurrences is important as well as investigation of causative agents. 0071 The 70-gene MammaPrint profile allows to identify a subgroup of very good-prognostic patients with primary breast cancer and 4−9 positive lymph nodes
PubMed, Oct 11, 1986
Ten patients with acute myeloid leukemia were treated with a high-dose ara-c regimen (3 g twice d... more Ten patients with acute myeloid leukemia were treated with a high-dose ara-c regimen (3 g twice daily for 6 days). 5 patients (50%) achieved a complete remission lasting for a median duration of 5 months. These patients had all achieved a complete remission following standard treatment with ara-c. High-dose ara-c was ineffective in 2 patients resistant to standard ara-c protocols. The most important side effects of high-dose ara-c were conjunctivitis and cerebellar symptomatology. In one case a severe diffuse encephalopathy with cerebellar predominance set in at a remarkably late stage (45 days after starting treatment). Our results and those of other authors suggest that treatment with high-dose ara-c should be used with caution.
PubMed, Nov 5, 1994
CYFRA 21-1 (CYFRA) is a new tumor-associated marker which appears to be useful in monitoring non-... more CYFRA 21-1 (CYFRA) is a new tumor-associated marker which appears to be useful in monitoring non-small cell bronchial carcinoma. We examined 193 sera from tumor patients (92 of whom had bronchial carcinoma), and 62 patients with benign lung disease. Sensitivity and specificity of CYFRA was compared with that of CEA, TPA, TPS and SCC in squamous cell bronchial carcinoma and with that of NSE in small cell bronchial carcinoma. The sensitivity of CYFRA in other tumor localizations was also assessed. In squamous cell bronchial carcinoma CYFRA proved to be the best marker with respect to sensitivity (58%) and specificity (98%). In gastrointestinal tumors CYFRA had a similar sensitivity to CEA. Since the two markers do not correlate their sensitivity is additive. In conclusion, CYFRA is confirmed as marker of first choice in squamous cell bronchial carcinoma. In other tumors CYFRA displayed a similar sensitivity to CEA.
PubMed, Nov 2, 1996
Regular blood transfusions in patients with beta-thalassaemia major lead to secondary hemochromat... more Regular blood transfusions in patients with beta-thalassaemia major lead to secondary hemochromatosis in the majority of cases. As a consequence of chronic iron overload, many endocrinopathies may occur. The most frequent endocrine dysfunction is hypogonadotropic hypogonadism, which is mainly responsible for osteopenia in as much as 80% of thalassemic patients. The frequencies of other endocrine disorders (hypothyroidism, diabetes mellitus and hypoparathyroidism) are lower. We investigated 5 female patients aged 22-25 years for endocrine dysfunction and bone density. All presented with hypogonadotropic hypogonadism and amenorrhea (four primary and one secondary). 4 patients showed absent or delayed pubertal development and short stature (below 10th percentile). In all five, hypogonadism is the most relevant cause of osteopenia as demonstrated by osteodensitometry. Endocrine disorders, especially absent pubertal development, should be detected in good time and treated with hormonal replacement. Established osteopenia is treated hormonally and with vitamin D3 and calcium.
Supportive Care in Cancer, 1994
In a prospective dose-escalation study tolerability and effectiveness of repeated infusions with ... more In a prospective dose-escalation study tolerability and effectiveness of repeated infusions with intravenous pamidronate were investigated. A total of 80 patients with proven malignancy and pain due to osteolytic bone disease were enrolled. Doses of 30 mg, 45 mg, 60 mg and 90 mg pamidronate, given every 4 weeks, 3 weeks or 2 weeks were tested. Thus dose intensity was increased by giving higher doses and/or by shortening the intervals. A combined palliation score on the bases of pain score (WHO), analgesic score (WHO) and improvement of performance status (SAKK/ECOG) was rated by the physician on a six-point scale. Regression analysis showed a close correlation between dose intensity and effect (Pearson's R = 0.7: P < 0.0001). A statistically significantly different palliative score for patients treated with low (below 15 mg/week), medium (16-30 mg/week) and high doses (above 31 mg/week) of pamidronate was found (P= < 0.01). A dose intensity below 10 mg pamidronate/ week and single doses of 30 mg had no clinically relevant benefit, whereas dose intensities of 25-45 mg/week showed a significant palliative effect. We conclude that pamidronate should be given in a close intensity of 20 mg per week or more in patients with far advanced osteolytic bone disease. Best results are obtained with high doses of 60 mg or 90 mg pamidronate. Further investigations by prospective randomized trials are needed to determine the optimal dose and schedule of pamidronate infusions.
European Journal of Haematology, Apr 24, 2009
A 65‐year‐old woman with B‐cell chronic lymphocytic leukemia (CLL) and pure red cell aplasia (PRC... more A 65‐year‐old woman with B‐cell chronic lymphocytic leukemia (CLL) and pure red cell aplasia (PRCA) is described. After initial chemotherapy with three different regimens over 3 months (prednisone, chlorambucil/vincristine, cyclophosphamide, bleomycin/cyclophosphamide, etoposide, prednisone), normalization of the blood lymphocyte count was observed, but lymphocyte infiltration of the bone marrow persisted and erythropoiesis remained virtually absent. Monotherapy with cyclosporin‐A (CyA) was begun. After 35 days, a marked increase in the reticulocyte count was observed, and with continuing therapy, there was a rapid increase in the hemoglobin level. Follow‐up after 13 months of uninterrupted treatment with CyA revealed remission of both CLL and PRCA. CyA should be investigated further as a therapeutic modality for PRCA in patients with CLL, and such trials might provide further clues to the pathogenesis of this peculiar association.
Annals of Oncology, Feb 1, 2000
Background: GI147211, a 10,11-ethylenedioxy substituted analogue of camptothecin (CPT), was broug... more Background: GI147211, a 10,11-ethylenedioxy substituted analogue of camptothecin (CPT), was brought into clinical development because of its higher water solubility and greater potency as compared to topotecan (TPT). The antitumor activity of GI147211 as second-line therapy in small-cell lung cancer (SCLC) was assessed after stratification of patients in refractory (no response to initial treatment or relapse within three months from last cycle) and chemosensitive (relapse more than three months from last cycle). Patients and methods: Sixty-seven patients were entered in the study and sixty-two were evaluable for response, twentyeight in the refractory and thirty-four in the chemosensitive group. All patients had received 1 line of chemotherapy; radiation had also been given in 29 cases, 6 in the refractory and 23 in the chemosensitive group. GI147211 was administered at 1.2 mg/m 2 /day as 30-min infusion for five consecutive days every three weeks. Results-The overall response rate was 16.6% (11 of 66 patients; 95% confidence interval (95% CI): 8.5%-27.5%), 10.3% (3 of 29 patients; 95% CI: 2.2%-27%) in the refractory and 21.1% (8 of 37 patients; 95% CI: 9.5%-37%) in the chemosensitive group. Only partial responses (PR) were observed with a median duration of PR of 4.8 months (5.7 months in the refractory and 5.2 in the chemosensitive group). Hematological toxicity consisted mainly of neutropenia (grades 3-4 in 25% of cycles) and thrombocytopenia (grades 3-4 in 23% of cycles); non-hematological toxicity was mild to moderate and consisted of nausea (22% of cycles), vomiting (11%), malaise (34%). Conclusions: At the dose and schedule tested GI147211 is an active new agent for second-line treatment of SCLC; the antitumor activity and toxicity profile are comparable to those observed with TPT which remains the leading CPT analogue for salvage treatment. Interest has been renewed in the clinical development of GI147211 by preclinical data with the liposomal formulation showing an increased therapeutic index.
Digestion, 1996
In an open phase III study, octastatin was given as a continuous subcutaneous (s.c.) infusion to ... more In an open phase III study, octastatin was given as a continuous subcutaneous (s.c.) infusion to 35 patients (mean age 62 years) with malignant neuroendocrine gastro-intestinal tumours and the carcinoid syndrome. The wash-out was often incomplete because of the advanced stage of disease. The starting dose of 1.5 mg/24 h was increased up to 3.0 mg/24 h at 3 months in some patients. The carcinoid syndrome disappeared in 20% of patients at 3 months and in 23% at 6 months, with 43 and 45% of patients, respectively, experiencing an improvement. The mean Karnovsky index increased by > 10% in 40% of patients at 3 and 6 months. Urinary 5-hydroxyindoleacetic acid (U-5-HIAA) levels at 3 months normalised in 1 patient, fell in 20% (by > 50%; p = 0.0021) and stabilised in 66%. The respective values at 6 months were 1, 17% (p = 0.023) and 60%. There was also a significant decrease in plasma chromogranin levels at 3 months (p = 0.042), which did not persist at 6 months. Tumour size fell (by > 50%) in 1 patient by 6 months but this patient had undergone chemoembolisation one month prior to the start of the study. Most patients had tumour size stabilisation (76 and 68%) or progression (20 and 24%) at 3 and 6 months, respectively. Dose escalation from 1.5 to 3.0 mg did not significantly improve clinical, biochemical or tumour responses. The treatment was well tolerated with minor adverse events. In an open pilot phase II study of 19 patients (mean age 58 years), patients were given high dose somatuline with a maintenance dose of 12,000 mg/day in 4 divided s.c. injections. U-5-HIAA, which was elevated in 13 patients with a mean of 444 mumol/day before the start, was reduced to 58% of baseline at 3 months, 68% at 6 months (p = 0.04), 66% at 9 months and 75% at 12 months (p = 0.14). P-chromogranin was elevated in 18 patients, with a mean of 5,300 micrograms/l before the start, and was reduced to 52, 55, 63 and 64% of the baseline at 3, 6 (p = 0.039), 9 and 12 (p = 0.013) months, respectively. In the responding patients, apoptosis was induced.
Urologia Internationalis, Jun 6, 2015
verse events were nausea and vomiting. Conclusion: Gefitinib in combination with chemotherapy did... more verse events were nausea and vomiting. Conclusion: Gefitinib in combination with chemotherapy did not improve efficacy in advanced urothelial cancer.
Annals of Oncology, May 1, 1995
Interferon (IFN) treatment trials in multiple myeloma have yielded discordant results regarding r... more Interferon (IFN) treatment trials in multiple myeloma have yielded discordant results regarding response rates, maintenance duration, and survival times. Further randomized trials and global evaluations of available data are urgently needed for clarification. 256 patients participated in a randomized trial, 125 on IFN + VMCP, and 131 on VMCP alone. 100 patients were randomized to IFN maintenance (n = 46) or were untreated controls (n = 54). Global evaluations are based on 1,518 patients in induction and 924 in maintenance trials. The induction trial demonstrated a significantly (p < 0.05) lower rate of progressive disease under IFN + VMCP (10.6%) than under VMCP (22.9%), but this benefit was limited to stage I or II patients. Median progression-free survival was longer in the IFN + VMCP arm (23.2 months vs. 15.8 months); median overall survival did not differ significantly (38.9 vs. 30.2 months). The IFN maintenance treatment trial showed significantly superior results in the IFN arm versus controls (median maintenance duration: 17.8 months and 8.2 months (p < 0.01), survival: 50.6 and 34.4 months (p < 0.05), respectively). Previous IFN treatment increased the benefits of IFN maintenance therapy. Adverse effects of IFN during induction were hematologic toxicity, fever, and infections, requiring dose reductions. Toxic effects of IFN maintenance treatment were mild. Global evaluations of randomized trials showed small but significant benefits of combined IFN induction therapy and significantly prolonged maintenance duration and survival under IFN maintenance. Presently available data support the use of IFN maintenance treatment because it significantly prolongs maintenance duration and survival. IFN added to induction chemotherapy resulted in minor improvements at the expense of increased toxicity, highlighting the need for better induction regimens.
Journal of Clinical Oncology, Apr 1, 2002
To determine the efficacy and tolerability of combining oxaliplatin with capecitabine in the trea... more To determine the efficacy and tolerability of combining oxaliplatin with capecitabine in the treatment of advanced nonpretreated and pretreated colorectal cancer. Forty-three nonpretreated patients and 26 patients who had experienced one fluoropyrimidine-containing regimen for advanced colorectal cancer were treated with oxaliplatin 130 mg/m(2) on day 1 and capecitabine 1,250 mg/m(2) bid on days 1 to 14 every 3 weeks. Patients with good performance status (World Health Organization grade 0 to 1) were accrued onto two nonrandomized parallel arms of a phase II study. The objective response rate was 49% (95% confidence interval [CI], 33% to 65%) for nonpretreated and 15% (95% CI, 4% to 35%) for pretreated patients. The main toxicity of this combination was diarrhea, which occurred at grade 3 or 4 in 35% of the nonpretreated and 50% of the pretreated patients. Grade 3 or 4 sensory neuropathy, including laryngopharyngeal dysesthesia, occurred in 16% of patients on both cohorts. Capecitabine dose reductions were necessary in 26% of the nonpretreated and 45% of the pretreated patients in the second treatment cycle. The median overall survival was 17.1 months and 11.5 months, respectively. Combining capecitabine and oxaliplatin yields promising activity in advanced colorectal cancer. The main toxicity is diarrhea, which is manageable with appropriate dose reductions. On the basis of our toxicity experience, we recommend use of capecitabine in combination with oxaliplatin 130 mg/m(2) at an initial dose of 1,250 mg/m(2) bid in nonpretreated patients and at a dose of 1,000 mg/m(2) bid in pretreated patients.
Oncology Research and Treatment, 2003
The insulin-like growth factor (IGF) system performs multiple functions in normal tissue. IGFs ar... more The insulin-like growth factor (IGF) system performs multiple functions in normal tissue. IGFs are involved in normal mammary gland development, but have also been implicated in the pathogenesis of breast cancer. Epidemiological studies found an association between elevated serum levels of IGF-I and an increased risk for breast cancer. IGF-I is the major mediator of growth hormone (GH) action. On the cellular level, IGF-I has a strong influence on cell proliferation and it is a potent inhibitor of apoptosis. Further, IGFs are also involved in angiogenesis. These characteristics are the basis for their involvement in maintenance and progression of cancer. The functions of IGF-I are mainly mediated through the type-I IGF-receptor (IGF-IR). The availability of free IGF-I for interaction with IGF-IR is modulated by IGF binding proteins (IGFBP 1-6). Based on interactions with other receptors, including estrogen and epidermal growth factor receptors, combined targeted therapies may improve breast cancer treatment.
Journal of Clinical Oncology, May 20, 2008
22170 Background: Preliminary reports indicate that dutasteride can suppress progesterone transfo... more 22170 Background: Preliminary reports indicate that dutasteride can suppress progesterone transformation into 5-alpha pregnane by SRD5A1 in breast cancer, resulting in suppression of cell proliferation and detachment. The aim of this study was to investigate SRD5A1 expression according to the breast cancer subtypes and patient characteristics. Methods: SRD5A1 mRNA expression levels were investigated in three breast cancer data sets consisting of a 64 genes Qrt-PCR data set (STB, 168 patients) and two micro-arrays data sets (295 and 286 patients). Results: SRD5A1 mRNA expression was found to be significantly higher in estrogen receptor (ER) negative tumors including the Basal like and HER2-positive subtypes. Moreover, elevated SRD5A1 were found to be associated with pre-menopausal status of the patients, high tumor grade and poor clinical outcome. Conclusions: SRD5A1 mRNA expression was found to be associated with ER-negative breast cancer phenotypes mainly found in tumors obtained from pre-menopausal wome...
Oncology Research and Treatment, 1993
operation while preserving functioning lung tissue. Discussed in this article are sleeve lobectom... more operation while preserving functioning lung tissue. Discussed in this article are sleeve lobectomy, an alternative to pneumoaectomy in patients with cancer in a lobar orifice; segmemectomy or wedge resection. an alternative to lobectomy in those with a peripheral lung cancer: and thoracoscopy, an alternative to open thoracotomy for various chest malignancies. Chemotherapy FOM: An etkctive, non-ciaplatin-baaed combination chemotherapy for advanced non-smukell lung cancer with low toxicity