Albumin-heparin microspheres as carriers for cytostatic agents

Much work has been done on adriamycin-loaded albumin microspheres (Alb-MS) for chemoembolization [1–4], the rationale being that site-specific drug delivery may increase the therapeutic efficacy of the drug. Alb-Ms are being investigated because of their biocompatibility and because the degradation products of these microspheres are non-toxic. However, these microspheres have some disadvantages (i.e. drug loading during the microsphere preparation, low payloads, large burst effects). These disadvantages can be overcome by the incorporation of heparin (a highly negatively charged mucopolysaccharide). Albumin-heparin microspheres were prepared (i) by crosslinking of soluble albumin and heparin first using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and subsequently glutaraldehyde (Alb-Hep-MS) and (ii) by crosslinking a preformed soluble conjugate of heparin and albumin with glutaraldehyde (Alb-Hep-Conj-MS). Albumin-heparin microspheres could be loaded with adriamycin after microsphere preparation giving payloads of 15–30%. Preliminary in vitro adriamycin release experiments showed that Alb-Hep-Conj-MS exhibit sustained release properties. Furthermore ion-exchange properties could be observed both with Alb-Hep-MS and Alb-Hep-Conj-MS. In vitro and in vivo toxicity experiments with Alb-Hep-MS showed no adverse effects

Phase II study of ACNU in non-small-cell lung cancer: EORTC study 08872

A total of 62 patients with metastatic or locally advanced non-small-cell lung cancer were entered in a phase II study of ACNU. Initially, the drug was given i. v. at a dose of 100 mg/m2 every 6 weeks, but due to observed haematological side effects in chemotherapy-pretreated patients, the dose was lowered in this group to 75 mg/m2. We observed one complete response in a subject exhibiting multiple lung metastases and a partial response in two patients, one showing brain metastases and one who experienced local disease recurrence. The toxicity of ACNU mainly consisted of bone marrow suppression especially thrombocytopenia, with one toxic death occurring due to intracerebral haemorrhage. We concluded that at this dose and on this schedule, ACNU has limited activity in non-small-cell lung cancer

Long-term body retention and tissue distribution of platinum in cisplatin-treated cancer-patients

Platmum levels have been determined in 145 samples from 24 tissues and 7 types of tumours from patients, treated with cisplatin. Sampled were 27 males (average age: 36 y, range: 22–63) and 19 females (average age: 52 y, range: 17–69), with an average total intravenous dose of 820 mg and 545 mg cisplatin, respectively. Samples were obtained via biopsy and autopsy, mostly 4–15 weeks after the last cisplatin administration. The long-term clearance of platinum from the tissues analyzed could be described by a first-order process with a half-life in the range of 175–300 days. The platinum fraction involved in the longterm total body clearance is estimated to be 22–38% of the total dose administered. However, the platinum clearance from a mature teratoma appeared to be much slower as measurable levels were detected 7.6 years after administration of the drug. The highest long-term platinum accumulations were found in liver, uterus, testes, ovary, and thyroid, and the lowest in brain and blood

Alga : a cancer patient profiling tool to improve physician-patient communication. an analysis in breast cancer patients

Background: Considerable improvement of communication between physicians and patients (pts) will need to occur as personalised medicine becomes the norm. An accurate profile of the pt\u2019s cognitive and psychological status should help the physician shape his language and his messages to maximise the pt\u2019s understanding of her management options. To this aim a computerized tool (ALGA questionnaire) has been created and validated. Methods: The validation process produced a questionnaire with 4 main factors: Health State Perception, Psychological, Psychosocial and Cognitive aspects. To test its ability to discriminate between healthy people and pts, ALGA has been administered to 50 newly diagnosed primary Breast Cancer (BC) pts prior to their first visit with the oncologist to discuss their adjuvant treatment, and to 50 healthy women (age range:20-60), using an iPad. Results: A multivariate analysis showed a significant difference between BC pts and healthy women relatively to the four aforementioned broad areas: Psychosocial (F(1,56)=13.42, p<.001), Cognitive (F(1,56)=6.53, p<.01), and Psychological Aspect (F(1,56)=2.77, p=.05). ALGA detected pts with higher levels of anxiety and depression. Pts tended to ruminate more than healthy subjects. Finally, pts showed higher level of positive Health State Perception, suggesting a dissociation between cancer illness and general health. Cognitive and Psychological aspects and Health State Perception interacted with participants\u2019 level of education (respectively: F(1,56)=12.23, p<.001; F(1,56)=4.58, p<.05; F(1,56)=7.9, p<.05). Starting from this results a personal profile for each pt was created. Conclusions: The ALGA confirmed ability to discriminate between healthy people and BC pts, and is a good tool to create a personal pt\u2019s profile with which physicians can empower patient with tailored knowledge. Starting from ALGA questionnaire, a smart environment is being implemented as a decision support infrastructure to help communication, interaction and information delivery process from doctor to patient, influencing patient\u2019s quality of life and satisfactio