ABSTRACT
Background: Pancreatic cancer is one of the most aggressive cancers, with comparatively poor outcomes despite the use of multiagent conventional chemotherapy regimens. Real-world data from clinical practice are still rare but are the basis for understanding and improving the current standard of care. Materials & methods: In this multi-institutional retrospective analysis of 24 office-based oncology practices in Germany, the authors documented 1786 pancreatic cancer patients who received systemic treatment between April 2017 and June 2021. Results: The authors' analysis showed that results from recent clinical studies are promptly incorporated into practice. Conclusion: It was striking that, during the analyzed period, the use of platinum-based therapy regimens in adjuvant and palliative first-line therapy increased predominantly in younger patients (<70 years).
Cancer of the pancreas is one of the most aggressive cancers, with poor survival despite the use of strong chemotherapy. Data from clinical practice are still rare but are the basis for understanding and improving the current standard of care. In this analysis of 24 office-based oncology practices in Germany, the authors documented treatment data of 1786 patients with pancreatic cancer who received chemotherapy between April 2017 and June 2021. The authors' analysis shows that results from recent clinical studies are promptly integrated into practice. The use of a certain type of chemotherapy with platinum increased, especially in patients younger than 70 years of age.
ABSTRACT
OBJECTIVES: Psychosocial distress is common in cancer patients and survivors and encompasses a broad range of concerns and psychological symptoms. The aim of the current study was to identify subgroups of respondents who experience a specific constellation of distress symptoms. METHODS: This study uses data from a large data base (n = 21 680) of cancer patients from diverse settings who provided data in the Questionnaire on Distress in Cancer Patients-Short Form (QSC-R10). Cluster analysis was applied to identify subgroups with a distinct constellation of distress symptoms. RESULTS: The results showed five distinct clusters: minimally distressed patients (46.6% of the sample), highly distressed patients (12.7%), mainly physically distressed patients (15.2%), mainly psychologically distressed patients (15.6%), and mainly socially distressed patients (9.9%). These groups differed with regard to age, sex, cancer site, treatment setting, and disease progression. CONCLUSION: The results revealed large heterogeneity in the experience of distress. Distress clusters were associated with socio-demographic and clinical variables. These associations might aid a clinician to tailor interventions and to address specific types of distress.
Subject(s)
Cancer Survivors/psychology , Cancer Survivors/statistics & numerical data , Neoplasms/epidemiology , Neoplasms/psychology , Psychological Distress , Adult , Female , Humans , Male , Middle Aged , RiskABSTRACT
Ovarian carcinomas show considerable heterogeneity of origin, both in terms of site and tissue. The most important and also most frequent of these tumors arise from the coelomic epithelium and are therefore characterized as epithelial ovarian carcinomas (EOC). EOC is often large and advanced at the time of presentation, so that cells are readily obtainable from surgical specimens or effusions. While the primary tumor may be chemosensitive, they often develop resistance and may do so rapidly. Due to the easy access to tumor cells and its biological behavior, EOC is considered to be an ideal model to investigate principal mechanisms of both antineoplastic drug sensitivity and resistance. Although studies on primary EOC cells are now preferred for many of these investigations, EOC cell line studies remain important too. This chapter gives an overview over major techniques required to establish and maintain primary EOC cell cultures and to initiate and cultivate permanently growing EOC cell lines.
Subject(s)
Cell Culture Techniques/methods , Cell Line, Tumor/pathology , Cell Separation/methods , Anti-Bacterial Agents/pharmacology , Carcinoma, Ovarian Epithelial , Cell Culture Techniques/standards , Cell Line, Tumor/drug effects , Cell Line, Tumor/microbiology , Cell Separation/standards , Cryopreservation , Female , Humans , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/pathology , Quality Control , SuspensionsABSTRACT
Previous data suggest that lipophilic statins such as fluvastatin and N-bisphosphonates such as zoledronic acid, both inhibitors of the mevalonate metabolic pathway, have anti-cancer effects in vitro and in patients. We have examined the effect of fluvastatin alone and in combination with zoledronic acid in the ATP-based tumour chemosensitivity assay (ATP-TCA) for effects on breast and ovarian cancer tumour-derived cells. Both zoledronic acid and fluvastatin showed activity in the ATP-TCA against breast and ovarian cancer, though fluvastatin alone was less active, particularly against breast cancer. The combination of zoledronic acid and fluvastatin was more active than either single agent in the ATP-TCA with some synergy against breast and ovarian cancer tumour-derived cells. Sequential drug experiments showed that pre-treatment of ovarian tumour cells with fluvastatin resulted in decreased sensitivity to zoledronic acid. Addition of mevalonate pathway components with zoledronic acid with or without fluvastatin showed little effect, while mevalonate did reduced inhibition due to fluvastatin. These data suggest that the combination of zoledronic acid and fluvastatin may have activity against breast and ovarian cancer based on direct anti-cancer cell effects. A clinical trial to test this is in preparation.
Subject(s)
Adenosine Triphosphate/metabolism , Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Enzyme Inhibitors/pharmacology , Mevalonic Acid/antagonists & inhibitors , Ovarian Neoplasms/drug therapy , Adenosine Triphosphate/antagonists & inhibitors , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols , Breast Neoplasms/enzymology , Breast Neoplasms/metabolism , Diphosphonates/pharmacology , Drug Screening Assays, Antitumor , Fatty Acids, Monounsaturated/pharmacology , Female , Fluvastatin , Humans , Imidazoles/pharmacology , Indoles/pharmacology , Middle Aged , Ovarian Neoplasms/enzymology , Ovarian Neoplasms/metabolism , Signal Transduction/drug effects , Tumor Cells, Cultured , Zoledronic AcidABSTRACT
Granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim [Leukine]) is a powerful cytokine that is able to stimulate the generation of dendritic cells. Adjuvant treatment with continuous low-dose GM-CSF has been shown to prolong survival of stage III/IV melanoma patients. Data on continuous low-dose GM-CSF therapy in tumors other than prostate cancer are still lacking. This pilot trial was initiated in order to evaluate the efficacy and tolerability of continuous low-dose GM-CSF as salvage in various chemotherapy-refractory carcinomas. A total of 19 patients who had failed a median of 4 prior chemotherapies were included. Their malignancies included metastatic breast cancer, recurrent ovarian carcinoma, metastatic endometrial carcinoma, and recurrent squamous cell cancer of the cervix uteri. Continuous low-dose GM-CSF was delivered subcutaneously at a daily starting dose of 125 microg. GM-CSF was increased at 25-microg increments until a maximum of 250 microg was reached or when mild leukocytosis (10-20 g/L) was achieved, providing that the relative eosinophil count did not exceed 15%. Therapy was continued until progression or refusal by the patient. Toxicity was generally mild. Only one patient was withdrawn due to grade 3 fatigue. In three additional patients, temporary dose reduction was necessary because of grade 1 injection site reactions, which recovered spontaneously. Mild to moderate leukocytosis was obvious in 10 patients. Systemic hypersensitivity-like reactions did not occur and no patient required hospitalization for other life-threatening side effects. The objective response rate was 37%: 1 complete and 6 partial responses, 4 disease stabilizations, 8 progression of disease. Median response duration was 6 months. Notably, 6 of 7 responders but only 1 of 8 patients with disease progression developed leukocytosis during therapy. Therefore, we conclude that continuous low-dose GM-CSF has substantial activity in heavily pretreated patients with either metastatic breast cancer or female genital tract cancer. Achievement of mild leukocytosis seems to be a predictor of response.