Biomedical subjects

A Santoro

Publications and source records attributed to A Santoro.

At least 73 records · Page 4Linked to original sources

PubMed2002

Three-week versus four-week schedule of cisplatin and gemcitabine: results of a randomized phase II study.

BACKGROUND: The cisplatin and gemcitabine (GC) regimen is usually administered as a 4- or 3-week schedule; however, the best schedule to use is still unclear. We therefore started a randomized phase II trial to compare toxicity and dose intensity (DI) between these two GC schedules. PATIENTS AND METHODS: Ninety-six patients with non-small-cell lung cancer (NSCLC) and an additional 11 patients with an advanced epithelial neoplasm [bladder (n = 5), head and neck (n = 3), cervix (n = 1), esophageal (n = 1) or unknown primary carcinoma (n = 1)] were randomized to receive cisplatin 70 mg/m(2) intravenously on day 2 plus either gemcitabine 1000 mg/m(2) on days 1, 8 and 15 of a 28-day cycle or gemcitabine 1000 mg/m(2) on days 1 and 8 of a 21-day cycle. Planned DI (PDI) for the 4-week schedule was 750 mg/m(2)/week for gemcitabine and 17.5 mg/m(2)/week for cisplatin; for the 3-week regimen PDI was 666 mg/m(2)/week and 23 mg/m(2)/week for gemcitabine and cisplatin, respectively. RESULTS: From July 1998 to March 2000, 107 patients were randomized. Grade 3/4 neutropenia was observed in 27.8% of patients in the 3-week versus 22.5% in the 4-week arm (P = 0.69), while grade 3/4 thrombocytopenia was higher in the 4-week arm (29.5% versus 5.5% of patients; P = 0.14). A total of 398 cycles of therapy were delivered. Overall, 51% of cycles were modified in dose, timing or both in the 4-week arm, and 19% in the 3-week arm. The 21-day schedule of GC leads to a similar received DI of gemcitabine and higher cisplatin DI. Both regimens had activity in NSCLC, with a response rate of 39% (38% for the 4-week arm, and 42% for the 3-week arm). CONCLUSIONS: The 3-week schedule has similar DI to the 4-week schedule. However the 3-week regimen has a better compliance profile and a comparable response rate in NSCLC, supporting the use of such a schedule.

Adult↗

PubMed2002

Irinotecan and raltitrexed: an active combination in advanced colorectal cancer.

BACKGROUND: Irinotecan and raltitrexed are active agents in metastatic colorectal cancer. Preclinical findings suggest a remarkable synergistic activity between the two drugs and the feasibility of this association has been shown in a recent phase I study. The aim of our phase II trial was to assess the efficacy and tolerability of the combination of irinotecan and raltitrexed in patients with metastatic colorectal cancer untreated with chemotherapy. PATIENTS AND METHODS: From June 1998 to February 2000, 46 patients were enrolled. Patients received irinotecan 350 mg/m(2) on day 1 and raltitrexed 2.6 mg/m(2) on day 2, every 3 weeks, for up to nine courses. Tumour assessment was performed every three cycles. RESULTS: A total of 223 cycles of chemotherapy, with a median number of six (range 1-9) courses per patient, was administered. According to intention-to-treat analysis, the overall response rate was 46% (95% confidence interval 31% to 61%). The median duration of response was 21 weeks (range 11-> or =101), the median time to progression 27 weeks (range 1-> or =116), and the median overall survival 57 weeks (range 1-> or =130). The main toxicities were diarrhoea, with National Cancer Institute common toxicity criteria grade 3/4 in 26% of patients, grade 3/4 neutropenia in 20%, grade 3 nausea-vomiting in 13%, grade 3 asthenia in 11% and grade 3/4 transaminase elevation in 4%. CONCLUSIONS: Results achieved with irinotecan and raltitrexed show that this regimen is active, despite 'not-negligible' toxicity, and may represent a useful regimen for specific subgroups of colorectal cancer patients.

Adult↗

PubMed2002

Intensified CHOP regimen in aggressive lymphomas: maximal dose intensity and dose density of doxorubicin and cyclophosphamide.

BACKGROUND: Following our previous study of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) intensification in non-Hodgkin's lymphoma (NHL), in the present report we attempted to further increase dose intensity by shortening the between-course intervals with the support of growth factors. PATIENTS AND METHODS: A total of 67 patients were enrolled. With a fixed dose of doxorubicin 75 mg/m(2), cyclophosphamide (CTX) was started at a dose of 1750 mg/m(2) and increased by 250 mg/m(2) in consecutive cohorts of patients provided that no dose-limiting toxicity occurred. After the maximal tolerated dose (MTD) had been identified, this was used to treat more patients in order to confirm the feasibility of the regimen on a large scale, with the number of cycles being varied on the basis of disease extension. RESULTS: Twenty-three cases were enrolled in the CTX dose finding phase. Dose-limiting non-hematological toxicity occurred at 2250 mg/m(2). As the intermediate level of 2000 mg/m(2) had a borderline toxicity profile, a CTX dose of 1750 mg/m(2) was defined as the MTD. A total of 53 patients then received the MTD during the course of the study as a whole. At the MTD, toxicity was acceptable. Only 10 of 189 cycles (4%) required hospitalization due to infection or febrile neutropenia. Seventy-four percent of the patients achieved complete remission. Freedom from progression and overall survival at 12 months were 71% and 86% in the whole series, and 58% and 71% for high-risk cases, respectively. CONCLUSIONS: This intensified CHOP regimen is feasible on an outpatient basis. It can be safely considered a definitive treatment in patients at low and intermediate risk, and as induction before high-dose consolidation in high-risk cases.

Adult↗

PubMed2002

A critical reappraisal of MIB-1 labelling index significance in a large series of pituitary tumours: secreting versus non-secreting adenomas.

Pituitary tumours are usually benign neoplasia, but may have a locally aggressive or malignant evolution. This study aimed to identify factors which mostly influence their proliferative activity, in order to clarify its value for clinical and research purposes. The proliferative index was determined in a prospective series of 132 pituitary tumours as the percentage of monoclonal antibody MIB-1-immunopositive cells and referred to as the MIB-1 labelling index (LI). Its distribution was analysed according to both univariate and multivariate models. A life-threatening pituitary tumour is presented separately. The mean LI was 1.24+/-1.59%, with significant differences between clinically secreting (CS) and clinically non-secreting (CNS) adenomas. In CS adenomas (n=65), LI was highly variable and markedly influenced by pre-operative pharmacological treatment (0.80+/-1.03 vs 2.06+/-2.39% in treated vs untreated cases, P=0.009); it decreased with patient's age (P=0.025, r=0.28) and increased with tumour volume and invasiveness. The influence of pre-operative treatment and macroscopic features on LI in this group was confirmed by multivariate analysis. In CNS adenomas (n=67), LI distribution was less variable than in CS adenomas (P<0.0001), it was age-independent and correlations with tumour volume, invasiveness or recurrence did not reach significance. In a rapidly growing parasellar tumour, the mean LI was 24% at first surgery and exceeded 50% at second surgery performed 4 months later. LI should be interpreted according to hormone secretion and pre-operative treatment. Unusually high LI values deserve particular attention.

Adenoma↗

PubMed2002

Surgical approaches to tumours of the lateral ventricles in the dominant hemisphere.

BACKGROUND: Intraventricular neoplasms are rare tumours (1% of the tumours of the central nervous system). The surgical approach sometimes is quite difficult, particularly in the dominant hemisphere. The best choice of surgical approach is discussed. METHODS: The authors describe a series of 25 patients who underwent surgical treatment for tumours situated in the lateral ventricles of the dominant hemisphere. They discuss the most influential factors in the choice of surgical approach, which must allow maximum exposure of the lesion and vascular feeding branches without damaging highly functional areas (motor, visual and language areas). In particular, they report their experience using a low transtemporal route, between the middle and inferior gyri, for removing tumours localized in the temporal horn and/or trigone which made it possible to keep postoperative visual and phasic deficits to a minimum. RESULTS: In 5 patients the approach was transfrontal, in 10 temporal, in 6 superior parieto-occipital and in 4 transcallosal. Three patients died. Only 5 patients presented permanent deficits (anomia, apraxia and visual fields alterations). CONCLUSIONS: The size, site, hemisphere and vascularization of intraventricular tumours influence the choice of surgical approach. The basal transtemporal approach is particularly indicated to remove tumours of the temporal horn and trigone and it seems to reduce the risk of speech disturbances and alterations of posture.

Cerebral Ventricle Neoplasms↗

PubMed2002

Brain metastases from hepatocellular carcinoma. A case report.

Brain metastasis from hepatocarcinoma are a decidedly rare occurrence in countries where this pathology is most frequent. The authors describe a case of metastases from hepatocellular carcinoma in a patient suffering from post-HBV hepatic cirrhosis with hemorrhagic onset. The "stroke-like" presentation of the cerebral localization of the disease can be explained by both the important vascularization of the tumor and the frequent hemocoagulative alterations caused by the cirrhosis. The importance of diagnostic neuroradiology is briefly addressed, with reference to the fundamental role played by MRI. Surgery of these lesions does not present any particular technical problems as long as they are located in accessible areas and the patient's general and neurological conditions allow it. Postoperative radiotherapy seems to improve the quality and quantity of residual life, although the number of patients described in the literature is too small to draw any definite conclusion. Promising molecular biology studies are under way to evaluate the role of oncosuppresor gene expression in hepatocarcinogenesis and in the way the disease spreads.

Brain Neoplasms↗

PubMed2002

Brain metastasis from hepatocellular carcinoma associated with hepatitis B virus.

Four cases of brain metastasis from hepatocellular carcinoma (HCC) associated with hepatitis B virus (HBV) are reported in an area not endemic for HBV infection. Two cases are unusual, since cerebral metastases were the only secondary localization. In these cases, no other sites of metastasization were detected either before or immediately following neurosurgical treatment. In all cases the expression of pRB, p53 and p16 tumor suppressor protein was studied with immunohistochemistry, both, in the primary and metastatic lesions. The pRB expression was as follows: in two cases, lack and moderate expression were observed both, in the primary and in the metastases; in the other two, pRB was not detected. In all cases p53 expression was negative both, in the primary and the metastases. P16 expression was moderately expressed in three cases, both in the primary and the metastases. In one case it was absent. Hepatocarcinogenesis is a multistep process, in which several oncogenes and oncosuppressor genes are involved. In four unusual cases of spread to the brain, we evidenced that tumor suppressor protein expression of p16, p53, and particularly pRB (its aberrated expression is usually associated with metastasis) were altered. We also suggest that HBV and its X protein (HBX) might play an important role in such aggressive behavior of the neoplasia.

Aged↗

PubMed2001

Combined regimen of cisplatin, doxorubicin, and alpha-2b interferon in the treatment of advanced malignant pleural mesothelioma: a Phase II multicenter trial of the Italian Group on Rare Tumors (GITR) and the Italian Lung Cancer Task Force (FONICAP).

BACKGROUND: The cisplatin-doxorubicin combination has shown moderate activity in malignant pleural mesothelioma (MPM; objective response, 25%), and preclinical studies suggest that interferons (IFNs) may have an antiproliferative effect on mesothelioma cell lines with a marked increase in cisplatin cytotoxicity. Therefore, the combined chemoimmunotherapy regimen is an worthwhile approach to evaluate in a Phase II trial. METHODS: From December 1995 to June 1999, 37 previously untreated patients with MPM were treated with cisplatin 60 mg/m(2) intravenously on Day 1 plus doxorubicin 60 mg/m(2), recycled every 3-4 weeks and IFN-alpha-2b, 3 x 10((6)) international units subcutaneously 3 times a week for a total of 6 courses or until progression. Inclusion criteria were histologic diagnosis of MPM and measurable disease defined by computed tomography scan or magnetic resonance imaging. RESULTS: Thirty-four patients were assessable for toxicity and 35 for efficacy according to World Health Organization criteria. One hundred thirty-five courses were administered with a median of 4 cycles per patients. Seventy-six percent of patient presented at least 1 episode of severe myelosuppression (Grade 3 and 4). Severe anemia and thrombocytopenia occurred in 30% and 24% of patients, respectively. Sixty percent of patients presented constitutional symptoms. In the 35 patients assessable for response, the overall response rate was 29% (95% confidence interval, 15-47%). The median duration of response was 8.4 months. With a median follow-up of 19.6 months, the median survival was 9.3 months. One- and 2-year survival was 45% and 34%, respectively. CONCLUSIONS: This combined regimen has definite activity in MPM. However, toxicity, particularly myelosuppression and fatigue, is not negligible and may limit its application.

Adult↗

PubMed2001

Surgical treatment and clinical outcome of GH-secreting adenomas in elderly patients.

Patients older than 65 years represent 3-5% of all acromegalic patients. The old age of the patients and the higher incidence of cardiovascular and metabolic complications related to acromegaly could increase the intra- and peri-operative risk, so that medical treatment is usually recommended as a therapy of choice. The aim of this retrospective study was to investigate the impact of transsphenoidal surgery in a series of 22 elderly patients with active acromegaly, with special regard to anaesthesiological risk, peri-operative complications, and clinical outcome. Despite an increased anesthesiological risk being present in 16/22 patients, no complication occurred during surgery. Similarly, no post-operative mortality or major complications were observed. Biochemical cure, defined at 6 months by glucose-suppressed plasma GH levels below 1 ng/ml and normal age-corrected IGF-I value levels, was achieved in 68% of patients and no recurrence of disease was observed in the subsequent follow-up (mean 5.2+/-2.1 years). A significant cardiovascular improvement was observed in cured patients, with a decrease of left ventricular mass index (91.3+/-20.1 vs 115.9+/-15.0 g/m(2); P<0.005), as measured by echocardiography, as well as a slight but significant decrease of systolic and diastolic blood pressure values (130.0+/-12.1 mmHg vs 137.6+/-13.5 mmHg P<0.05; and 84.2+/-6.4 mmHg vs 88.8+/-7.5 mmHg P<0.05, respectively). A significant post-operative improvement of glucose tolerance was also observed in this group. We conclude that transsphenoidal surgery, if well planned and carefully performed, is safe and able to induce a significant cardiovascular and metabolic improvement even in elderly acromegalic patients.

Acromegaly↗

PubMed2001

A randomised phase II study on neo-adjuvant chemotherapy for 'high-risk' adult soft-tissue sarcoma.

The aim of this study was to examine the strategy, feasibility and outcome of neo-adjuvant chemotherapy, with doxorubicin and ifosfamide, in adult patients with 'high-risk' soft-tissue sarcomas. Patients with 'high-risk' soft-tissue sarcomas, defined as tumours > or =8 cm of any grade, or grade II/III tumours <8 cm, or grade II/III locally recurrent tumours, or grade II/III tumours with inadequate surgery performed in the previous 6 weeks and therefore requiring further surgery, were randomised between either surgery alone or three cycles of 3-weekly doxorubicin 50 mg/m(2) intravenous (i.v.) bolus and ifosfamide 5 g/m(2) (24 h infusion) before surgery. The type of surgery had to be planned at randomisation. Tumours were to be amenable to surgery by amputation, compartmental resection, wide or marginal excision. If chemotherapy was given, surgery had to be performed within 21 days after the last chemotherapy. Patients received postoperative radiotherapy in cases of marginal surgery, microscopically incomplete resection and no further possibility for surgery, and in cases of surgery because of local recurrence. 150 patients were entered into the study and 134 were eligible, 67 in each arm. The most frequent side-effects of chemotherapy were alopecia, nausea and vomiting (95%), and leucocytopenia (32%). One patient died of neutropenic fever after the first cycle of chemotherapy. Chemotherapy did not interfere with planned surgery and did not affect postoperative wound healing. Limb-salvage was achieved in 88%, amputation was necessary in 12% (all according to the plan at randomisation). The trial was closed after completion of phase II, since accrual was too slow to justify expanding the study into the scheduled phase III study. At a median follow-up of 7.3 years, the 5 year disease-free survival is estimated at 52% for the no chemotherapy and 56% for the chemotherapy arm (standard error: 7%) (P=0.3548). The 5 year overall survival for both arms is 64 and 65%, respectively (standard error 7%) (P=0.2204). Neo-adjuvant-chemotherapy with doxorubicin and ifosfamide at these doses and with this schedule was feasible and did not compromise subsequent treatment, surgery with or without radiotherapy. Although not powered to draw definitive conclusions on benefit, but with an at least 7 year median follow-up, the results render it less likely that major survival benefits will be achieved with this type of chemotherapy.

Adolescent↗

PubMed2001

Mobilizing potential of ifosfamide/vinorelbine-based chemotherapy in pretreated malignant lymphoma.

The mobilizing potential and therapeutic activity of ifosfamide/vinorelbine-containing regimens with G-CSF support were explored in patients with pretreated malignant lymphomas. Ten patients with non-Hodgkin's lymphoma (NHL) received ifosfamide and vinorelbine, and 17 with Hodgkin's disease (HD) received ifosfamide, vinorelbine and gemcitabine (IGEV regimen), as induction chemotherapy before high-dose chemotherapy (HDT) with peripheral blood stem cell (PBSC) support. Most of the patients had been heavily pretreated with various chemotherapy regimens +/- radiotherapy. The target yield was > or =3 x 10(6) CD34+ cells/kg of body weight in order to support the subsequent myeloablative chemotherapy. The optimal PBSC harvest occurred on days 11 and 12, with no difference in CD34+ cell mobilization kinetics between the ifos- famide/vinorelbine and IGEV regimens. The median number of CD34+ cells/kg body weight collected was 10.9 x 10(6) (range 1.76-61.1 x 10(6)). The median total CD34+ cell/microl, CFU-GM and white blood cells (WBC) for all individual collections was 81.5/microl, 10 x 10(4)/kg, and 17 900/microl, respectively. The target yield of CD34+ cells was reached in 24 of 27 patients. Hematological side-effects were acceptable and no treatment-related hospitalizations or toxic deaths occurred. Fifteen patients have so far received high-dose therapy and PBSC reinfusion with rapid engraftment. These results confirm that ifosfamide and vinorelbine-based chemotherapy regimen with G-CSF support can be successfully and safely used to mobilize PBSCs.

Adult↗

PubMed2001

Allogeneic peripheral blood stem cell transplantation with reduced intensity conditioning in primary refractory prolymphocytic leukemia: graft-versus-leukemia effect without graft-versus-host disease.

A patient with progressive prolymphocytic leukemia (PLL) received an allogeneic stem cell transplant using a reduced intensity conditioning regimen to avoid prohibitive toxicities. Early in the post-transplant period, a high donor-derived CD8+ count was observed. One year from transplantation, the patient was in complete remission, fully donor chimeric and with a normal performance status, suggesting that this approach may represent a useful treatment option in patients with refractory PLL.

Female↗

PubMed2001

Detection of BCR/ABL rearrangements in adult acute lymphoblastic leukemia using a highly sensitive interphase fluorescence in situ hybridization method (D-FISH).

INTRODUCTION: One hundred-and-six adult cases of acute lymphoblastic leukemia were prospectively investigated using a highly sensitive interphase fluorescence in situ hybridization assay which utilizes DNA probes that detect a double BCR/ABL fusion signal (D-FISH) in cells carrying the t(9;22) to evaluate the reliability and specificity of this method for the detection of the Ph translocation. The results were compared with those obtained in the same cases by conventional cytogenetics and by reverse-transcription polymerase chain reaction. MATERIALS AND METHODS: The study was performed using DNA probes that span the common breakpoints of the t(9;22) translocation and that detect a double BCR/ABL fusion in cells carrying this karyotypic anomaly, one on the abnormal chromosome 9 and one on the Ph chromosome. RESULTS: Interphase D-FISH detected a high number of rearranged cases (22/106) compared to conventional cytogenetics (15/106) and RT-PCR (21/106). CONCLUSION: Interphase D-FISH emerges as a reliable, fast and relatively inexpensive tool for the detection of BCR/ABL rearrangements in adult ALL patients at diagnosis. It has a sensitivity clearly higher than conventional karyotyping and it may prove also superior to that of RT-PCR in cases with unusual BCR/ABL breakpoints. Our results suggest that D-FISH might be considered as the initial test for the diagnosis of Ph+ adult ALL.

Adolescent↗

PubMed2001

Marked improvement in cardiovascular function after successful transsphenoidal surgery in acromegalic patients.

OBJECTIVE: Transsphenoidal surgery results in biochemical remission of acromegaly in 45-80% of patients; however, few studies have addressed the impact of transsphenoidal surgery on cardiovascular function in acromegalic patients. The aim of this prospective study was to investigate the effects of postoperative GH/IGF-I normalization on echocardiographic parameters and blood pressure (BP) in a series of patients with active acromegaly. DESIGN: An open prospective study. PATIENTS: Thirty newly diagnosed acromegalic patients undergoing transsphenoidal surgery. MEASUREMENTS: Doppler echocardiography and 24-h ambulatory blood pressure monitoring were performed before and 6 months after transsphenoidal surgery. RESULTS: Fifteen patients were considered to be well controlled postoperatively (group A), as defined by normal age-corrected IGF-I levels and glucose-suppressed GH levels less than 2 mU/l, the remaining 15 patients being considered as poorly controlled (group B). In group A, a postoperative decrease of left ventricular mass index was observed (104.4 +/- 6.6 vs. 127.1 +/- 7.7 g/m2; P < 0.001), associated with an improvement of some indices of diastolic function, such as an increase of the early/late transmitral peak flow velocity (P < 0.05) and a decrease of isovolumic relaxation time (P < 0.01). No significant change was observed in group B. A significant decrease of 24-h systolic BP was also observed in group A (P < 0.05) and five of six patients normalized their BP circadian rythm. In contrast, a nonsignificant increase in BP values, with a persistent blunted BP profile where present, was observed in group B. CONCLUSIONS: We conclude that successful transsphenoidal surgery is able to induce a significant improvement in some cardiac parameters and a slight reduction in systolic blood pressure in acromegalic patients.

Acromegaly↗

PubMed2001

Dry weight in hemodialysis: volemic control.

In dialysis patients the chronic fluid overload may represent a nonphysiologic condition which brings both arterial hypertension and hemodynamic instability. Volume expansion is significantly correlated to casual predialysis blood pressure and 24-hour arterial pressure. The normalization of the patient hydration status is not only followed by a reduction in pressure values but also by an improvement of the circadian blood pressure rhythm. On the other hand, hypovolemia and underhydration combined with an impaired cardiovascular regulatory response may generate the dialysis-related hypotension. Many techniques have been introduced to obtain an objective measurement of the hydration status: postdialysis radiological chest examination, plasma atrial natriuretic peptide (ANP), and plasma cyclic guanidine monophosphate (cGMP) levels, multifrequency electrical bioimpedance and the continuous plasma volume measurement. The latter, alone or in combination with provocative tests (stop and go of the ultrafiltration), may help in optimizing plasma volume contraction. The plasma volume monitoring avoids the risk of hypovolemic hypotension and facilitates the achievement of a correct dry body weight. The biofeedback system, exploiting the automatic control of the intradialytic variations, may represent an additional advantage in the formulation of an ideal postdialysis blood volume that overlaps the patient's dry weight.

Body Weight↗

PubMed2001

Assessment of skin safety of a new glyceryl trinitrate transdermal patch. Animal and human studies.

The experimental models and the studies in man employed to assess the skin and general safety of a newly developed glyceryl trinitrate (GTN, CAS 55-63-0) transdermal patch, hereinafter coded EPI, are described. EPI was found well tolerated by the skin after single or 28-day repeated epicutaneous application on the rabbit, devoid of phototoxicity in the mouse, devoid of skin sensitizing potential in the guinea pig and devoid of photosensitizing effects in the guinea pig. Tested were also, with negative results, the cytotoxic, hemolytic and genotoxic potential, the presence of bacterial endotoxins, the systemic and intracutaneous toxicity, and the possible conjunctival irritant effects. The application of EPI for 14 consecutive days on the thoracic skin of 28 healthy volunteers did not provoke subjective discomfort such as itching, burning or pain, or objective skin lesions. On the application site a light and transient erythema was often found demonstrating the transcutaneous absorption of the vasodilating GTN from the patch. The 14-day application was followed after two weeks by the application of a challenge EPI patch to detect a possible skin sensitization by EPI. No skin reaction was elicited, showing that also in man EPI is devoid of skin sensitizing potential. During the 14-day application of EPI several GTN commonly induced systemic adverse reactions were observed, particularly headache, confirming the systemic bioavailability of GTN from the patch. Headache rapidly disappeared after removal of the patch, in parallel with the decrease of the blood concentrations of GTN and of its active metabolites, consistently with the previous pharmacokinetic findings. This is an advantage of the administration of GTN with the transdermal patch because, in the case of unbearable headache, the patient is relieved by the simple removal of the patch.

Adhesives↗

PubMed2001

Development of patches for the controlled release of dehydroepiandrosterone.

Dehydroepiandrosterone (DHEA) and its sulfate conjugate (DHEAS) are the major secretory steroidal products of the adrenal gland. Some epidemiologic studies have found an association between low DHEA serum levels in patients and many important diseases. To prevent all such pathological conditions and, in any case, in aging, a DHEA supplementation has been proposed. DHEA shows a low oral bioavailability; taking the bioavailability obtained by the subcutaneous route as 100%, it was estimated that the potencies of DHEA by the percutaneous and oral routes were approximately 33% and 3%, respectively. Thus, transdermal patches could be considered a promising formulation as a continuous and controlled delivery of DHEA in replacement therapy is desired. With the aim of evaluating the effect of the matrix composition in terms of polymers and enhancers on the DHEA skin permeation flux, 10 types of monolayer self-adhesive patches containing 0.25mg/cm2 of active ingredient were designed. The matrices were based on three different acrylic copolymers: an acrylate-vinylacetate copolymer, a polyaminomethylmethacrylate (PAMA), and a polymethylmethacrylate. Transcutol (TR), mint essential oil, Lauroglycol, Brij 58, and propylene glycol (PG) were evaluated as DHEA skin permeation enhancers. All prepared patches were characterized by drug content, light microscopy, and in vitro skin permeation, performed using a modified Franz-type diffusion cell and human stratum corneum and epidermis as a membrane. The in vitro skin permeation studies are particularly significant in the development studies of DHEA patches as the in vivo determination of DHEA is affected b the fact that the endogen substance in the plasma is not constant over time. Among the testedpatches, highest DHEA fluxes were obtained using the formulation based on PAMA. Moreover, the introduction in the matrix of binary mixtures of TR and PG, used also for their plasticizer properties, permitted enhancing DHEA skin permeation. On the basis of these studies, the transdermal administration of DHEA using patches seems feasible.

Administration, Cutaneous↗

PubMed2001

Clinical significance of neuroendocrine phenotype in non-small-cell lung cancer.

Non-small-cell lung carcinoma (NSCLC) describes a histologically heterogeneous group of tumours with variable clinical behaviour. Performance status, tumour stage and histological type have important prognostic implications, but clinical outcomes in individual patients remain unpredictable. A significant minority of NSCLCs (10%-30%) show neuroendocrine (NE) differentiation, and a number of studies have attempted to evaluate the therapeutic and prognostic significance of the expression of NE markers on the basis of the theoretical assumption that NE-differentiated tumours may be associated with an adverse prognosis and greater chemosensitivity. However, the results of these studies are conflicting: some have found that NE differentiation has a negative impact on survival, but others have failed to demonstrate any correlation with prognosis. Similar discrepancies have also been observed in terms of chemosensitivity. Nevertheless, these data are difficult to interpret because there is no gold standard defining NE differentiation, as is shown by the fact that the proportion of NE-differentiated NSCLCs varies according to the technique and marker used, although chromogranin A and synaptophysin show the best correlation with ultrastructural evidence of NE differentiation. In conclusion, there is no doubt that caution is required when interpreting the results of a number of studies questioning the clinical impact of the NE features of NSCLCs.

Antineoplastic Agents↗