Biomedical subjects

Olaf M Koch

Publications and source records attributed to Olaf M Koch.

4 recordsLinked to original sources

PubMed2006

Surgery in the tri-modality treatment of small cell lung cancer. Stage-dependent survival.

OBJECTIVE: Patients with small cell lung cancer (SCLC) are frequently denied surgical treatment despite growing body of evidence for a longer duration of remission and overall survival, if surgical intervention is integrated in a tri-modality therapy concept including chemotherapy, surgery, and radiotherapy. METHODS: A retrospective analysis was performed using data derived from 95 patients with SCLC operated upon over a period of 9 years. A subset of these patients was primarily operated upon and being diagnosed as SCLC only after thoracotomy, received radio-/chemotherapy postoperatively (n=64, group I). The second cohort had surgery after neoadjuvant chemotherapy which was continued postoperatively in addition to thoracic and cranial radiotherapy (n=31, group II). The patients in the second group were further divided into two subgroups: complete histological regression of tumor tissue in the mediastinal lymph nodes (group IIA), and those with persistent mediastinal lymph nodal involvement detected after thoracotomy (group IIB). RESULTS: Group I patients had stage I or II disease, whereas group II patients had clinical stage IIIA or IIIB. The overall 30-day mortality rate was as low as 5%. The median survival was 31.3 months for patients in group I, 31.7 months for adjuvant surgery with complete regression of mediastinal nodes (group IIA), and 12.4 months for adjuvant surgery without regression of mediastinal nodes (group IIB). CONCLUSIONS: Surgical intervention is promising and warrants prospective trials to be evaluated as an important adjunct to multi-modality therapy regimen in SCLC as regards to its impact on relapse free and overall survival.

Adult↗

PubMed2003

Hyperfractionated cyclophosphamide in combination with pulsed dexamethasone and thalidomide (HyperCDT) in primary refractory or relapsed multiple myeloma.

Sixty patients with advanced multiple myeloma received 2-6 monthly treatment courses combining hyperfractionated cyclophosphamide (300 mg/m2 i.v. over 3 h q 12 h x 6, d 1-3) with pulsed dexamethasone (20 mg/m2/d p.o., d 1-4, 9-12, 17-20) and once daily thalidomide at individually escalating doses (100-400 mg/d) depending on tolerability (HyperCDT). Responding patients were maintained on daily thalidomide and monthly dexamethasone pulses. Complete, partial and minor response rates were 4%, 68% and 12% respectively; overall response rate was 84% (efficacy analysis). Median event-free and overall survival was 11 and 19 months respectively. During at least one treatment cycle, 67% of patients experienced grade 4 neutropenia resulting in 17% grade 3 and 9% grade 4 infections. Side-effects, presumably related to thalidomide, included neuropathy (40% grade 2, 16% grade 3), constipation (17%), oedema (5%), bradycardia (5%), skin reactions (3%), cerebrovascular events (5%) and deep vein thromboses (8%). Thromboses were not related to known thrombophilic risk factors. Four patients with prior myeloma therapy > 50 months developed myelodysplastic syndrome or secondary acute myeloid leukaemia 2-4 months after study entry. HyperCDT is a highly active and reasonably well-tolerated salvage regimen in advanced or refractory multiple myeloma.

Acute Disease↗

PubMed2003

Synergistic growth inhibitory effects of interferon-alpha and lovastatin on bcr-abl positive leukemic cells.

The chimeric bcr-abl tyrosine kinase is of crucial pathogenic importance in chronic myeloid leukemia (CML). As shown, bcr-abl activates the ras pathway by phosphorylation of adapter proteins such as Grb-2 and Crkl. Functional inhibition of p21ras might partially inhibit the mitogenic signaling by bcr-abl. By depletion of cellular mevalonate pools, p21ras proteins can be rendered non-functional as a result of deficient post-translational protein farnesylation. We investigated the pharmacologic effect of mevalonate depletion by lovastatin in conjunction with interferon-alpha 2b (INF-alpha 2b) in bcr-abl positive K562 cells. At various concentrations, both drugs synergistically reduced cell proliferation of CML line K562 in a liquid culture system as well as clonal growth of colony forming units in a patient with newly diagnosed CML. Lovastatin and IFN-alpha 2b in combination led to cell cycle arrest and resulted in significant reduction of phosphorylation on tyrosine, serine, and threonine protein residues. IFN-alpha 2b alone showed little effect on protein phosphorylation but strongly enhanced lovastatin driven loss of phosphorylation. Subsequently, DNA fragmentation occurred in 50% of cells. In conclusion, exposure to IFN-alpha 2b and lovastatin synergistically inhibited proliferation of bcr-abl positive cells and resulted in loss of protein phosphorylation and subsequent apoptosis in K562 cells. Our in vitro model suggests further investigations are required of the potential value of HMG-CoA reductase inhibitors as adjunct to therapy of CML with interferon.

Antineoplastic Agents↗

PubMed2002

Fatigue as an important aspect of quality of life in patients with acute myeloid leukemia.

Quality of life (QL) was evaluated in 101 patients with AML undergoing intensive and prolonged treatment at 12 sequential time points by using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C 30 questionnaire and the profile of mood states scale (POMS). For those patients having completed the course of inpatient treatment (n=37), QL improved from the beginning of chemotherapy to the end of inpatient treatment. Patients who subsequently went off protocol did not differ significantly in their self-assessed QL when compared with patients who completed therapy. Fatigue was more closely related to QL than nausea/emesis or appetite loss, but did not correlate with hemoglobin levels.

Adolescent↗