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C Curcio

Publications and source records attributed to C Curcio.

At least 19 recordsLinked to original sources
PubMed2007

WIP null mice display a progressive immunological disorder that resembles Wiskott-Aldrich syndrome.

The Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency syndrome caused by mutations in the WAS protein (WASP). This participates in signalling and cytoskeletal homoeostasis, and some of its activities are regulated by its binding to the WASP interacting protein (WIP). WIP deficiency, however, has not yet been shown to be of pathological significance in humans. Here we show that, in WIP null (WIP(-/-)) mice, it produces haematological alterations and anatomical abnormalities in several organs, most probably as a consequence of autoimmune attacks. Granulocytosis and severe lymphopenia are associated with a proportional increase in segmented cells and fewer bone marrow erythrocytes and lymphocytes. Splenomegaly is accompanied by an increase of haematopoietic tissue and red pulp, reduction of the white pulp, and fewer B (B220(+)) lymphocytes (also apparent in the lymph nodes and Peyer's patches). Ulcerative colitis, interstitial pneumonitis, glomerular nephropathy with IgA deposits, autoantibodies, and joint inflammation are also evident. These progressive immunological disorders closely mimic those seen in WAS. WIP deficiency may thus be implicated in some cases in which mutations in the gene encoding WASP are not detected.

Animals↗
PubMed2003

A novel dominant missense mutation--D179N--in the GJB2 gene (Connexin 26) associated with non-syndromic hearing loss.

Mutations of the GJB2 gene, encoding Connexin 26, are the most common cause of hereditary congenital hearing loss in many countries, and account for up to 50% of cases of autosomal-recessive non-syndromic deafness. By contrast, only a few GJB2 mutations have been reported to cause an autosomal-dominant form of non-syndromic deafness. We report on a family from southern Italy in whom dominant, non-syndromic, post-lingual hearing loss is associated with a novel missense mutation in the GJB2 gene. Direct sequencing of the gene showed a heterozygous G-->A transition at nucleotide 535, resulting in an aspartic acid to asparagine amino acid substitution at codon 179 (D179N). This mutation occurred in the second extracellular domain (EC2), which would seem to be very important for connexon-connexon interaction.

Amino Acid Substitution↗
PubMed2002

Indication of hysteroscopy in tamoxifen treated breast cancer patients.

The aim of this study was to indicate the patients treated with tamoxifen for breast cancer in which hysteroscopy with biopsy should be considered mandatory. 414 breast cancer patients who underwent hysteroscopy with bioptic evaluation were enrolled in the study. 334 subjects were treated with 20 mg of tamoxifen daily as adjuvant therapy for six up to a hundred months. Of the remaining 80 control patients, which had not received tamoxifen, 30 were in premenopause (Group IA) and 50, in postmenopause (Group IIA). The tamoxifen-treated patients were subdivided in premenopausal (Group IB = 72 patients) and in postmenopausal (Group IIB = 262 patients) groups. All patients were further classified in asymptomatic or symptomatic groups considering whether uterine bleeding was absent or present. The evaluation of the endometrial mucosa was performed by office hysteroscopy. In group IIB patients presenting uterine bleeding, malignant lesions were found in 7.8% of the cases. The incidence of premalignant and malignant lesions in IIB patients treated for longer than 3 years (11.7%) was higher than that observed in IIB patients treated for less than 3 years (1.3%). There was a significant difference in terms of endometrial pathology between Group IIB (32.8%) and Group IIA (8%) (p < 0.001); and between Group IIB (32.8%) and Group IB (13.9%) women (p = 0.003). Among IA and IIA patients there were no cases of endometrial hyperplasia or cancer; on the contrary, in IB and IIB women, 2 and 22 cases of atypical hyperplasia were observed, respectively. All cases of endometrial cancer were observed in Group IIB and had a diagnosis of poor prognosis. In conclusion the hysteroscopy with biopsy should be considered the first diagnostic procedure to perform in tamoxifen-treated postmenopausal patients presenting uterine bleeding and in postmenopausal women treated for longer than 3 years. In premenopause, hysteroscopy should be proposed to women with ultrasonographic abnormalities and/or with uterine bleeding to patients at high risk for endometrial cancer.

Antineoplastic Agents, Hormonal↗
PubMed2001

The contribution of 700,000 ORF sequence tags to the definition of the human transcriptome.

Open reading frame expressed sequences tags (ORESTES) differ from conventional ESTs by providing sequence data from the central protein coding portion of transcripts. We generated a total of 696,745 ORESTES sequences from 24 human tissues and used a subset of the data that correspond to a set of 15,095 full-length mRNAs as a means of assessing the efficiency of the strategy and its potential contribution to the definition of the human transcriptome. We estimate that ORESTES sampled over 80% of all highly and moderately expressed, and between 40% and 50% of rarely expressed, human genes. In our most thoroughly sequenced tissue, the breast, the 130,000 ORESTES generated are derived from transcripts from an estimated 70% of all genes expressed in that tissue, with an equally efficient representation of both highly and poorly expressed genes. In this respect, we find that the capacity of the ORESTES strategy both for gene discovery and shotgun transcript sequence generation significantly exceeds that of conventional ESTs. The distribution of ORESTES is such that many human transcripts are now represented by a scaffold of partial sequences distributed along the length of each gene product. The experimental joining of the scaffold components, by reverse transcription-PCR, represents a direct route to transcript finishing that may represent a useful alternative to full-length cDNA cloning.

Expressed Sequence Tags↗
PubMed2001

The human type 2 iodothyronine deiodinase is a selenoprotein highly expressed in a mesothelioma cell line.

Types 1 and 3 iodothyronine deiodinases are known to be selenocysteine-containing enzymes. Although a putative human type 2 iodothyronine deiodinase (D2) gene (hDio2) encoding a similar selenoprotein has been identified, basal D2 activity is not selenium (Se)-dependent nor has D2 been labeled with (75)Se. A human mesothelioma cell line (MSTO-211H) has recently been shown to have approximately 40-fold higher levels of hDio2 mRNA than mesothelial cells. Mesothelioma cell lysates activate thyroxine (T(4)) to 3,5,3'-triiodothyronine with typical characteristics of D2 such as low K(m) (T(4)), 1.3 nm, resistance to propylthiouracil, and a short half-life ( approximately 30 min). D2 activity is approximately 30-fold higher in Se-supplemented than in Se-depleted medium. An antiserum prepared against a peptide deduced from the Dio2 mRNA sequence precipitates a (75)Se protein of the predicted 31-kDa size from (75)Se-labeled mesothelioma cells. Bromoadenosine 3'5' cyclic monophosphate increases D2 activity and (75)Se-p31 approximately 2.5-fold whereas substrate (T(4)) reduces both D2 activity and (75)Se-p31 approximately 2-3-fold. MG132 or lactacystin (10 microm), inhibitors of the proteasome pathway by which D2 is degraded, increase both D2 activity and (75)Se-p31 3-4-fold and prevent the loss of D2 activity during cycloheximide or substrate (T(4)) exposure. Immunocytochemical studies with affinity-purified anti-hD2 antibody show a Se-dependent increase in immunofluorescence. Thus, human D2 is encoded by hDio2 and is a member of the selenodeiodinase family accounting for its highly catalytic efficiency in T(4) activation.

Acetylcysteine↗
PubMed2001

Expression and prognostic significance of urokinase and plasminogen activator inhibitor type-1 in endometrial hyperplasia and cancer.

Proteolytic enzymes, like urokinase (uPA) and plasminogen activator inhibitor type-1 (PAI-1), are involved in remodelling tissues during invasion and metastasis of tumor cells. The purpose of the study is to evaluate the expression and the prognostic significance of these enzymes in endometrial hyperplasia and cancer. We used immunohistochemical staining to localize uPA and PAI-1 antigens and evaluate their expression, and the enzyme-linked immunosorbent assay (ELISA) to measure their levels during the progression of endometrial carcinoma. The results show that the levels of uPA and PAI-1 detection are systematically weak in simplex hyperplasia and are moderate in complex hyperplasia. In the endometrial carcinoma a very strong reaction was observed in the most aggressive variant of epithelial tumors. A positive signal for uPA was found only in the cytoplasm of normal and hyperplastic cells while, in tumors, uPA was present also in the cellular areas surrounding the neoplastic glands and at the apex of the malignant cells. The PAI-1 immunoreactivity was weak to moderate in 95.4% of carcinomas, with a diffuse signal mostly distributed in the cytoplasm of neoplastic cells and tumor stroma. UPA antigen concentrations were significantly higher in endometrial carcinoma than in endometrial hyperplasia (p<0.05) and in normal endometrium (p<0.001). PAI-1 antigen concentrations in carcinoma samples were significantly higher than in normal endometrium (p=0.002), but the difference was not statistically significant with respect to that in endometrial hyperplasia. We did not find any correlation between uPA and PAI-1 concentrations and the standard prognostic parameters for evaluating endometrial carcinoma. In conclusion, this study demonstrates that in hyperplastic endometria and in endometrial carcinoma there is a progressive increase in expression of uPA and PAI-1 than in normal endometrial tissue. In carcinoma tissues, the high expression of uPA is unregulated in the surrounding stroma tissue, particularly in the most aggressive histopathologic variants. UPA and PAI-1 may be factors associated with invasive behavior in endometrial carcinoma independent of other clinicopathological parameters.

Adenocarcinoma↗
PubMed2000

Identification of human chromosome 22 transcribed sequences with ORF expressed sequence tags.

Transcribed sequences in the human genome can be identified with confidence only by alignment with sequences derived from cDNAs synthesized from naturally occurring mRNAs. We constructed a set of 250,000 cDNAs that represent partial expressed gene sequences and that are biased toward the central coding regions of the resulting transcripts. They are termed ORF expressed sequence tags (ORESTES). The 250,000 ORESTES were assembled into 81,429 contigs. Of these, 1, 181 (1.45%) were found to match sequences in chromosome 22 with at least one ORESTES contig for 162 (65.6%) of the 247 known genes, for 67 (44.6%) of the 150 related genes, and for 45 of the 148 (30.4%) EST-predicted genes on this chromosome. Using a set of stringent criteria to validate our sequences, we identified a further 219 previously unannotated transcribed sequences on chromosome 22. Of these, 171 were in fact also defined by EST or full length cDNA sequences available in GenBank but not utilized in the initial annotation of the first human chromosome sequence. Thus despite representing less than 15% of all expressed human sequences in the public databases at the time of the present analysis, ORESTES sequences defined 48 transcribed sequences on chromosome 22 not defined by other sequences. All of the transcribed sequences defined by ORESTES coincided with DNA regions predicted as encoding exons by genscan. (http://genes.mit.edu/GENSCAN.html).

Chromosomes, Human, Pair 22↗
PubMed2000

Phenotypic variability in Bartter syndrome type I.

Limited phenotypic variability has been reported in patients with Bartter syndrome type I, with mutations in the Na-K-2Cl cotransporter gene (BSC). The diagnosis of this hereditary renal tubular disorder is usually made in the antenatal-neonatal period, due to the presence of polyhydramnios, premature delivery, hypokalemia, metabolic alkalosis, hypercalciuria, and nephrocalcinosis. Among nine children with hypercalciuria and nephrocalcinosis, we identified new mutations consistent with a loss of function of the mutant allele of the BSC gene in five. Three of the five cases with BSC gene mutations were unusual due to the absence of hypokalemia and metabolic alkalosis in the first years of life. The diagnosis of incomplete distal renal tubular acidosis was considered before molecular evaluation. Three additional patients with hypokalemia and hypercalciuria, but without nephrocalcinosis in the first two and with metabolic acidosis instead of alkalosis in the third, were studied. Two demonstrated the same missense mutation A555T in the BSC gene as one patient of the previous group, suggesting a single common ancestor. The third patient presented with severe hypernatremia and hyperchloremia for about 2 months, and a diagnosis of nephrogenic diabetes insipidus was hypothesized until the diagnosis of Bartter syndrome type I was established by molecular evaluation. We conclude that in some patients with Bartter syndrome type I, hypokalemia and/or metabolic alkalosis may be absent in the first years of life and persistent metabolic acidosis or hypernatremia and hyperchloremia may also be present. Molecular evaluation can definitely establish the diagnosis of atypical cases of this complex hereditary tubular disorder, which, in our experience, may exhibit phenotypic variability.

Amino Acid Sequence↗
PubMed1999

Cell death in age-related macular degeneration.

The cellular and molecular mechanisms underlying the death of photoreceptors and other retinal cells in age-related macular degeneration (AMD) remain poorly understood. Some of the questions for which answers need to be sought, and which are explicitly or implicitly addressed in this article include: (1) how do patterns of cell death in AMD compare, qualitatively and quantitatively, with "normal" cell death in aging retinas, and with cell death in retinitis pigmentosa (RP) and its animal models; (2) is apoptosis involved in AMD; (3) is there any evidence that rods are necessary for cone survival; (4) if the answer is yes, is there evidence that rods produce one or more survival-promoting factor(s) that act directly on cones; (5) are the effects of rods upon cones exclusively mediated by diffusible factors, or do they also involve contact-mediated interactions; (6) is there any evidence that photoreceptors regulate the survival and/or function of RPE and Müller cells, as well as the interactions between these cells and cones; (7) are trophic factors and their receptors in the macula different from those in other parts of the retina; and (8) are toxic mechanisms involved in the onset and progression of cell death in AMD? Clear cut answers to most of these (and related) questions about cell death in AMD are not yet available. The goal of this article is to summarize discussion that should help in the formulation of suitable hypotheses, amenable to experimental analysis. To provide a platform for such discussion, we present an overview of progress made in recent years in the analysis of other retinal degenerations and of neuronal degenerations in other regions of the CNS. We conclude with an overview of concepts and speculation derived from our current research.

Aging↗
PubMed1999

Development of compensatory thermogenesis in response to overfeeding in hypothyroid rats.

Intact or surgically thyroidectomized (Tx) adult male Wistar rats, weighing 150-200 g, were fed a standard chow diet (approximately 1.8 Cal/g) or a high calorie (approximately 3.8 Cal/g) diet (cafeteria diet) for up to 30 days. Daily energy intake was about 5-fold higher in the rats fed the cafeteria diet regardless of their thyroid status. The cafeteria diet caused the retroperitoneal white fat pad to increase by approximately 2-fold, the volume of isolated white adipocytes to increase by 2-fold, and the total body fat to increase by a factor of approximately 3, again regardless of thyroid status. It also increased basal metabolic rate by about 20% in intact rats and by about 50% in Tx rats. The brown fat thermal response to norepinephrine (NE) infusion was approximately 2-fold increased in the intact rats fed the cafeteria diet. However, in the Tx rats, the brown fat thermal response to NE was blunted regardless of the dietary regimen adopted. In both intact and Tx rats, the cafeteria diet increased total brown fat mitochondria, uncoupling protein percentage, and total brown fat uncoupling protein by about 3-, 2-, and 5-fold, respectively. Serum leptin levels also increased approximately 4-fold in intact rats fed the cafeteria diet. However, in Tx rats, leptin levels did not change significantly during overfeeding. In conclusion, hypothyroidism caused the brown fat to become unresponsive to NE, even after 1 month on the cafeteria diet. However, these rats were able to increase basal metabolic rate and, as assessed by several different parameters, did not gain fat beyond that observed in intact controls kept on a similar overfeeding schedule.

Adipose Tissue↗
PubMed1998

Carboplatin plus vinorelbine, a new well-tolerated and active regimen for the treatment of extensive-stage small-cell lung cancer: a phase II study. Gruppo Oncologico Centro-Sud-Isole.

PURPOSE: To evaluate the activity and toxicity of the combination carboplatin plus vinorelbine in extensive small-cell lung cancer (SCLC). PATIENTS AND METHODS: A two-stage optimal Simon design was applied. To proceed after the first stage, responses from 8 of 11 treated patients were needed. Overall, 31 responses of 43 treated patients were required to comply with the design parameters. Inclusion criteria were cytohistologically proven SCLC; extensive disease; age of 70 years or less; Eastern Cooperative Oncology group performance status (ps ECOG) of 2 or less; normal cardiac, hepatic, renal, and bone marrow functions; and no previous chemotherapy. Patients were staged by physical examination; biochemistry; chest radiograph; brain, thoracic; and abdominal computed tomographic (CT) scans, and bone scan. All patients received carboplatin 300 mg/m2 intravenously (i.v.) day 1 and vinorelbine 25 mg/m2 i.v. on days 1 and 8 every 4 weeks up to six cycles. Of 43 enrolled patients, 36 were men and 7 women, with a median age of 63 years (range, 46 to 70 years). RESULTS: All patients were assessable for response and toxicity. We observed 32 (74%) objective responses, with 23% complete responses. Median time to progression was 25 weeks, and median survival was 37 weeks. The treatment was well tolerated. The reported main toxicities were leukopenia grade 3 in 21% of patients and grade 4 in 5% of patients, anemia grade 2 in 11% of patients and grade 3 in 2% of patients, and thrombocytopenia grade 3 in 7% of patients. CONCLUSION: These data show that carboplatin plus vinorelbine is an active and well-tolerated regimen in extensive SCLC. In view of the activity, low toxicity, and ease of administration, it may be a reasonable alternative to more toxic cisplatin-containing regimens.

Aged↗
PubMed1996

Partial substitution of cisplatin with carboplatin in combination with etoposide in advanced non-small cell lung cancer (NSCLC): a multicentric randomised phase II trial.

Seventy previously untreated patients with advanced NSCLC were randomised, after stratification for stage (IIIB vs. IV) and Performance Status (0-1 vs. 2), to receive either treatment A: CDDP 40 mg/m2 + VP16 100 mg/m2 day 1-3 (37 patients); or treatment B: CBDCA 250 mg/m2 day 1 + CDDP 30 mg/m2 day 2, 3 + VP16 100 mg/m2 day 1-3 (33 patients). Therapy was recycled on day 29 in both arms. The two arms were well balanced for the main pretreatment characteristics. Sixty-six patients (32 with Stage IIIB and 34 with Stage IV disease) were evaluable for toxicity and response (arm A = 34, arm B = 32), while four ineligible patients were excluded from analysis. Acute toxicity was assessed at recycling. Non-hematologic toxicity was higher in arm A. However, the reduction of nephrotoxicity (9% vs. 23%) in arm B was lower than expected. Leukopenia (15 vs. 5 patients) or thrombocytopenia (7 vs. 0 patients) of any grade affected more patients of arm B. Moreover, Grade 3-4 leukopenia (six patients) or thrombocytopenia (four patients) was observed only in arm B. Seventeen patients responded: 11/34 (32%; 95% C.I. = 17-50%) in arm A, and 6/32 (19%; 95% C.I. = 7-36%) in arm B. Median survival times of 40 and 34 weeks, respectively, were reported in arm A and B. Stage IIIB and squamous cell histology were associated with a higher probability of response. In conclusion, the partial replacement of CDDP with CBDCA in combination with VP16 slightly improves the tolerance of the treatment in terms of nephro- and neurotoxicity; however, it induces a significant increase in hematologic toxicity. In view of this unfavourable toxicologic profile and of the discouraging response rate observed, this regimen cannot be recommended as standard treatment in advanced NSCLC.

Adult↗
PubMed1996

Cisplatin/carboplatin + etoposide + vinorelbine in advanced non-small-cell lung cancer: a multicentre randomised trial. Gruppo Oncologico Campano.

A multicentre randomised phase III trial in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) was undertaken to compare the therapeutic activity and toxicity of a cisplatin/carboplatin-etoposide-vinorelbine combination with that of a cisplatin-etoposide regimen. Patients with advanced (stage IIIB-IV) NSCLC were randomised, after stratification for stage (IIIB-IV) and performance status (0-1 and 2), to receive either (A) CDDP 40 mg m-2 + VP16 100 mg m-2 on days 1-3 as standard treatment or (B) CBDCA 250 mg m-2 on day 1 + CDDP 30 mg m-2 on days 2 and 3 + VP16 100 mg m-2 on days 1-3 + NVB 30 mg m-2 on day 1. Therapy was recycled on day 29 in both arms. We hypothesised a 15% minimum increment in the response rate with the experimental regimen over the 25% expected activity rate of the standard regimen. A two-stage design was chosen, which permitted the early termination of the trial (after the accrual of 52 patients in each arm) if the difference in response rates between the two regimens was less than 3% at the end of the first stage. A total of 112 patients (arm A = 57, arm B = 55) were enrolled in the study (53 with stage IIIB and 59 with stage IV), of which 105 eligible patients were evaluable for response on an "intention to treat' basis. Seven patients were excluded because they did not fulfil the inclusion criteria. Fifteen responses were observed in arm A (28%, 95% CI = 17-42) and 13 (one complete) in arm B (25%, 95% CI = 13-37). On multivariate logistic analysis, treatment did not affect the response rate, while stage IV and performance status 2 were significantly associated with a lower probability of response. Median survivals were similar in the two arms (31 vs 27 weeks). The experimental regimen was associated with an extremely poor median survival in patients with poor performance status (21 weeks). On Cox analysis, treatment failed to show a significant impact on survival: stage IV (relative risk = 1.6. CI = 1.0-2.6, P = 0.036) was the only prognostic variable significantly associated with a worse survival outcome and, although poor performance status adversely affected survival, this effect did not reach the level of statistical significance (relative risk = 1.6, CI = 0.98-2.5; P = 0.063). There were no significant differences in non-haematological toxicities between the two arms, although three patients in the control arm had to discontinue the treatment because of the persistence of severe nephrotoxicity (two patients) or neurotoxicity (one patient). In contrast, a significant increase in both neutropenia and thrombocytopenia was observed in the experimental arm. Four treatment-related deaths were registered in arm B (two due to neutropenic sepsis, one to myocardial failure and one to acute renal failure) compared with one toxic death (acute renal failure) in arm A. In view of these results, the trial was stopped and the null hypothesis (< 15% increase in response rate with the experimental regimen) has been accepted. Therefore, our combination does not deserve further evaluation as first-line treatment in advanced NSCLC patients. As our data suggest that an aggressive chemotherapy might have a negative impact on survival of patients with poor performance status, trials to evaluate the activity of new regimens should be conducted separately for each subset of patients with different performance status.

Adenocarcinoma↗
PubMed1996

Phase I study of chemotherapy with carboplatin, epirubicin, and escalating dose of VP-16 with G-CSF support in extensive small cell lung cancer.

In attempt to develop a new chemotherapeutic regimen including carboplatin (CBDCA), epirubicin (EPI), and VP-16 in extensive small cell lung cancer, with a higher dose intensity compared with previous experience of our group, we determined the maximum tolerated dose (MTD) of VP-16 when administered in association with CBDCA (300 mg/ m2, i.v., day 1) and EPI (75 mg/m2, i.v., day 1), recycling chemotherapy every 3 weeks, with the support of granulocyte-colony-stimulating factor (G-CSF). A total of 15 patients received three dose levels of VP-16 (mg/m2, i.v., daily on days 1-3): 100 (three patients), 120 (six), and 140 (six). G-CSF was administered subcutaneously at the dose of 5 micrograms/kg/day on days 6-15 of each chemotherapy course. The MTD was established at 140 mg/m2 and myelotoxicity, grade 4 neutropenia with death for sepsis in one case and grade 3 thrombocytopenia in three cases, was dose limiting. The recommended dose of VP-16 for a phase II study is 140 mg/m2.

Adult↗
PubMed1995

DMD and BMD in the same family due to distinct mutations.

We report on a family with a boy affected by Duchenne muscular dystrophy (DMD) and an asymptomatic cousin with a Becker-type dystrophin abnormality, diagnosed by chance. Dystrophin gene analysis showed that these conditions were caused by two distinct deletions with breakpoints in different exons. In Xp21 families, DNA analysis and dystrophin testing of asymptomatic males with high CK plasma levels might detect different dystrophin mutations in separate haplotypes as in our family, although we stress there should be clear clinical or familial indications for such testing.

Adolescent↗
PubMed1994

Alternated approach with local irradiation and combination chemotherapy including cisplatin or carboplatin plus epirubicin and etoposide in intermediate stage non-small cell lung cancer.

BACKGROUND: Prognosis of unresectable non-small cell lung cancer (NSCLC) patients is disappointing; their median survival time does not exceed 8-12 months. Recently, some authors reported an increased response rate and sometimes a prolonged survival for patients with intrathoracic disease treated with local irradiation combined with cytotoxic drugs. METHODS: Fifty-eight consecutive patients with Stage IIIA or IIIB NSCLC were enrolled in a randomized Phase II trial of alternated treatment composed of four courses of combination chemotherapy and three cycles of local irradiation. Chemotherapy consisted of a randomly selected platinum compound (cisplatin [60 mg/m2] or carboplatin [300 mg/m2]) intravenously (i.v.) on Day 1, epirubicin (50 mg/m2) i.v. on Day 1, and etoposide (100 mg/m2) i.v. on Days 1-3. A course of radiotherapy consisted of 5 consecutive fractions (3 Gy per fraction, 1 fraction per day) for a total dosage of 15 Gy per course. Each course of chemotherapy was alternated every 2 weeks with a course of irradiation so that the entire treatment was performed in 13 weeks. RESULTS: Of the 58 patients, 53 were evaluable for response: 7 showed a complete clinical remission, and 25 reached a partial response, giving an overall response rate of 60% (95% confidence interval, 46%-74%). The tumors of four patients who showed a complete or partial response subsequently were surgically resected, and the complete disappearance of any residual tumor cells was documented histologically in two of them. No difference in response was observed between cisplatin- (16 of 26 [62%]) and carboplatin-treated patients (16 of 27 [59%]), and no correlation was found between response and either stage or histology. Patients enrolled in the carboplatin arm experienced less severe leukopenia and vomiting than did those in the cisplatin arm. Median freedom from progression and overall survival time were 28 and 39 weeks, respectively. Patients who responded had a significantly longer median duration of survival (49 weeks) as compared to non-responders (15 weeks). CONCLUSIONS: The alternated chemoradiotherapy treatment obtained a high response rate with substantial toxicity. This approach did not seem to improve the prognosis of patients significantly. In this setting, the administration of carboplatin instead of cisplatin appeared to be tolerated better by the patients.

Aged↗