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Biomedical subjects

A Daponte

Publications and source records attributed to A Daponte.

At least 37 records · Page 2Linked to original sources
PubMed1999

Estrogen replacement therapy for ovarian carcinoma survivors: A randomized controlled trial.

BACKGROUND: Surgery for premenopausal and perimenopausal patients with epithelial ovarian carcinoma may often result in significant menopausal symptoms. Physicians may well be reluctant to prescribe, and patients loathe to take, postoperative estrogen replacement therapy because they fear that supplementation may lead to ovarian carcinoma relapse. This randomized prospective study was undertaken to determine whether postoperative estrogen replacement therapy had a negative influence on the disease free interval and overall survival of ovarian carcinoma survivors. METHODS: Between January 1987 and June 1994, at the time of a routine consultation held 6-8 weeks postoperatively, 130 patients younger than 59 years with invasive epithelial ovarian carcinoma were randomized to continuous oral conjugated equine estrogen (ERT) or to no supplementation (non-ERT). All patients were followed prospectively for a minimum of 48 months. RESULTS: Three patients in the ERT group and 2 in the non-ERT group were lost to follow-up, so 59 and 66 were finally analyzed in their respective groups. Nine patients originally randomized to ERT refused or stopped their supplementation, whereas 5 in the non-ERT commenced taking estrogens. A total of 32 recurrences occurred in the ERT group and 41 in the non-ERT group. The median disease free interval was 34 versus 27 months, respectively, whereas overall survival was 44 versus 34 months, respectively, for the two groups. The differences in disease free interval (P = 0.785) and overall survival (P = 0.354) between the two groups were not statistically significant. CONCLUSIONS: Postoperative estrogen replacement therapy did not have a negative influence on the disease free interval and overall survival of ovarian carcinoma survivors.

Adult↗
PubMed1999

Management of diabetic pregnant patients in a tertiary center in the developing world.

OBJECTIVES: To audit our insulin regimen in our antenatal diabetics. METHODS: 170 pregnant diabetic patients were retrospectively analyzed. RESULTS: The perinatal mortality rate was 37/1000, vs. a perinatal mortality rate of 30/1000 in our setting. Cesarean section rate was 49%. Strict blood-glucose control reduced the incidence of macrosomia and polyhydramnios. Routine amniocentesis for fetal-lung maturity was not practiced. CONCLUSION: Satisfactory results in pregnant diabetic patients are achievable with an established insulin regimen in a developing country.

Adult↗
PubMed1999

Polymerase chain reaction-based detection of circulating melanoma cells as an effective marker of tumor progression. Melanoma Cooperative Group.

PURPOSE: Reverse transcriptase (RT) polymerase chain reaction (PCR) with multiple markers has been demonstrated to be highly sensitive in detecting circulating cells from patients with malignant melanoma (MM). We evaluated the clinical significance of the presence in peripheral blood of specific PCR-positive mRNA markers as an expression of circulating melanoma cells. PATIENTS AND METHODS: Total cellular RNA was obtained from the peripheral blood of 235 patients with either localized (n = 154) or metastatic (n = 81) melanoma. We performed RT-PCR using tyrosinase, p97, MUC18, and MelanA/MART1 as gene markers. The PCR products were analyzed by gel electrophoresis and Southern blot hybridization. In addition, 20 healthy subjects and 21 patients with nonmelanoma cancer were used as negative controls. RESULTS: Although detected at various levels among assessable patients, each mRNA marker was significantly correlated with disease stage. A significant correlation with disease stage was demonstrated for patients who were positive to all four markers (P < .0001) or to at least three markers (P < .001). Univariate analysis showed a significant correlation between risk of recurrence (evaluated in stage I, II, and III patients) and increasing number of PCR-positive markers (P = .0002). Logistic regression multivariate analysis indicated that each single marker (except tyrosinase) and, more especially, the presence of four PCR-positive markers remained statistically independent prognostic factors for tumor progression. CONCLUSION: Our data establish the existence of a significant correlation among clinical stages, tumor progression, and presence of circulating melanoma-associated antigens in peripheral blood of MM patients. Preliminary assessment of a subset of patients with a higher risk of recurrence needs longer follow-up and further studies to define the role of RT-PCR in monitoring MM patients.

Adult↗
PubMed1999

3-year treatment with recombinant interferon-alpha as adjuvant therapy of cutaneous malignant melanoma.

Interferon alpha (IFN alpha) has been demonstrated to possess a significant biological activity for cutaneous malignant melanoma (CMM). Although multiple adjuvant trials utilizing IFNá have been tested, no consensus on the optimal dosing schedule has been reached. From February 1993 to October 1997 we enrolled 86 CMM patients using low doses of IFN alpha-2b (3 MU/d TIW SC for 3 years) in a phase II study. Our present data show a median disease-free survival (DFS) of 30 months (range 2-62), comparable to those obtained in high-dose IFN alpha trials. These findings suggest that positive results may be also obtained using low doses of IFN alpha in adjuvant treatment of CMM patients. in contrast to the high dose, the low dose regimen was well tolerated with an acceptable quality of life of patients.

Chemotherapy, Adjuvant↗
PubMed1998

Weekly paclitaxel-cisplatin administration with G-CSF support in advanced breast cancer. A phase II study.

PURPOSE: In a previous phase I study we found the MTDs of paclitaxel and cisplatin when given together weekly, with or without G-CSF support, in patients with advanced solid tumors. The present study was conducted to define the toxicity and efficacy of this regimen, when used with G-CSF support, in chemotherapy-naive or pretreated patients with advanced breast cancer, and to compare the antiproliferative activity of paclitaxel-cisplatin and paclitaxel-doxorubicin combinations on two human breast cancer cell lines. METHODS: Patients with metastatic breast cancer received weekly paclitaxel (as a 3-hour i.v. infusion) at the dose of 85 mg/m2 (75 mg/m2 in pretreated women) followed by cisplatin (40 mg/m2) for a minimum of 6 weeks. An additional 6 weekly cycles were delivered in patients showing absence of documented disease progression after the first 6 weeks. After the 12th cycle only patients who had shown a substantial tumor shrinkage received 6 further cycles. G-CSF 5 microg/kg was also given, SC on days 3 to 5 of each week, for the whole duration of chemotherapy. The combination of paclitaxel with cisplatin or doxorubicin was also tested in vitro on two breast cancer cell lines (MCF-7 and MDAMB-231). RESULTS: Forty-three women with metastatic breast cancer entered this trial between June 1995 and January 1997. Twenty-seven patients were previously untreated for their metastatic disease (but 23 had previously received adjuvant chemotherapy). The dominant site of disease involvement was visceral in 23, bone in 13, and soft tissues in 7 patients. Seven complete and 15 partial responses were observed in unpretreated patients, while no complete and 6 partial responses were achieved in the pretreated population. The overall response rate, assessed on an 'intent to treat' basis, was 81% (26% CRs) in patients unpretreated for metastatic disease and 37% in those who had received one or more previous chemotherapy regimens. Eighteen responder patients had previously received anthracyclines either as adjuvant chemotherapy (12) or in the treatment of metastatic disease (6). At a median potential follow-up of 12 (range, 3-21) months, 14/27 unpretreated and 12/16 pretreated patients had shown disease progression. The median time to treatment failure was 13 and 7 months, respectively, in the 2 subgroups. The 1-year survival probability was 95% in unpretreated patients. The treatment showed a moderate toxicity in both subgroups of patients. Both hematological toxicity and peripheral neuropathy occurred more frequently in pretreated patients. Treatment-related deaths did not occur, and severe myelosuppression was observed only in pretreated patients with massive liver involvement. Delays in chemotherapy administration were very uncommon, especially during the first 6 treatment cycles, and the average actually delivered dose intensity exceeded 90% in unpretreated patients. The in vitro data on MCF-7 and MDA-MB-231 human breast cancer cell lines showed that exposure to the combination of cisplatin and paclitaxel produced a tumor cell killing similar to that achievable with equivalent concentrations of doxorubicin and paclitaxel. CONCLUSIONS: Weekly paclitaxel and cisplatin with G-CSF support is an active and particularly well tolerated treatment for patients with either unpretreated or pretreated metastatic breast cancer. This approach seems quite effective also in patients relapsing after anthracycline-based adjuvant chemotherapy. In view of the negligible hematological toxicity associated with this regimen, further clinical trials testing the addition of non cross-resistant drugs to this combination should be performed.

Adult↗
PubMed1997

Fotemustine and dacarbazine plus recombinant interferon alpha 2a in thetreatment of advanced melanoma.

Forty-three consecutive patients with advanced melanoma not previously treated with cytotoxic drugs (22 of them had already received adjuvant recombinant interferon alpha 2a (rIFN alpha 2a)) were given a combination of intravenous (i.v.) fotemustine (FM), 100 mg/m2 on day 1, and dacarbazine (DTIC), 250 mg/m2 i.v. on days 2-5, every 3 weeks. rIFN alpha 2a was administered at the dosage of 3 MIU subcutaneously 3 times a week until progression. Four complete and 13 partial responses were registered, for an overall response rate of 40% (95% CI, 25-56%). Activity of this regimen was similar in patients with mainly visceral (10/22, 45%) or soft tissue (6/13, 46%) involvement. The median duration of responses was 24 weeks. Median survival time was 40 weeks, with a 13% 2 year survival rate. Neutropenia and thrombocytopenia affected 67% and 51% of patients, but were of WHO grade 4 in only 2% and 5% of them, respectively. Side-effects attributable to rIFN alpha 2a were mild and manageable. In conclusion, the combination of FM + DTIC and rIFN alpha 2a seemed well tolerated and relatively active in patients with advanced melanoma. However, the role of rIFN alpha 2a in affecting the long-term outcome of patients is still questionable.

Adult↗
PubMed1997

Cisplatin-paclitaxel weekly schedule in advanced solid tumors: a phase I study.

PURPOSE: The objective of our study was to determine the maximum tolerable doses (MTDs) of both paclitaxel and cisplatin when given in a weekly schedule alone or simultaneously with G-CSF in advanced solid neoplasms. PATIENTS AND METHODS: Patients with advanced cancer either chemotherapy-naive or resistant to standard treatments received paclitaxel in a three-hour infusion followed by cisplatin, with or without the addition of r-HuG-CSF (5 micrograms/kg s.c. days three to five). The starting doses of CDDP and paclitaxel were 25 mg/m2/week and 45 mg/m2/week, respectively. During the first six courses the dosages of the two drugs were alternately escalated by 20% (CDDP = 5 mg/m2/week, and paclitaxel 10 mg/m2/week) at each step until the appearance of dose-limiting toxicity (DLT) in one-third or more of the patients enrolled in that cohort. RESULTS: Fifty-five patients with cancer (16 lung, 16 breast, 11 ovarian, 7 head and neck, 1 renal, 1 esophageal, 1 cervical, 1 soft-tissue sarcoma, and 1 of unknown primary), 25 of whom were pretreated, were entered into the study. A total of 439 weekly courses were delivered. In chemotherapy-naïve patients, the MTDs of cisplatin and paclitaxel were 30 mg/m2/week and 65 mg/m2/week, respectively, in the absence of G-CSF support, which increased to 40 mg/m2/week and 85 mg/m2/week, respectively, when G-CSF was given. There were no toxic deaths in this study. Neutropenia was the main dose-limiting toxicity (100/439 courses), but was seldom severe. Neurotoxicity was quite frequent (18 of 55 patients for the total of 88 courses) but never dose-limiting. It was more frequent and clinically relevant in cisplatin-pretreated patients. Overall 18 patients (eight ovarian, five breast, three lung, and two head and neck) achieved objective responses. CONCLUSIONS: The cisplatin-paclitaxel weekly administration seems a safe, practical and effective therapeutical approach in patients with advanced solid neoplasms. Large phase II trials are warranted to accurately define the efficacy of this schedule in cisplatin-paclitaxel sensitive tumors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Weekly paclitaxel and cisplatin with concurrent radiotherapy in locally advanced non-small-cell lung cancer: a phase I study.

PURPOSE: Both cisplatin (CDDP) and paclitaxel have shown good antitumor activity in non-small-cell lung cancer (NSCLC) patients and are able to potentiate the antitumor effects of radiation therapy (RT). This study aimed to determine the maximum-tolerated doses (MTDs) of CDDP and paclitaxel (escalated alternately) when given concurrently with RT and to define the nature of the dose-limiting toxicity (DLT). PATIENTS AND METHODS: Chemotherapy-naive patients with locally advanced NSCLC received six weekly administrations of a CDDP-paclitaxel combination with concurrent local RT. The starting doses of CDDP and paclitaxel were 30 mg/m2/wk and 35 mg/m2/wk, respectively. RT was initially given at the dose of 1.2 Gy twice daily for 5 days per week for 5 weeks (total dose, 60 Gy) and at a single daily dose of 2 Gy for 5 days per week for 6 weeks in the last two cohorts of patients. The drug doses were escalated alternately until DLT occurred in more than one third of the patients in a given cohort. RESULTS: Overall, 25 patients were recruited through five different cohorts. All were assessable for toxicity. Esophagitis was the main toxicity and occurred in 16 of 25 patients (64%) and was grade 3 or 4 in five of them. At step 3 (CDDP 35 mg/m2/wk and paclitaxel 45 mg/m2/wk), two of five patients had to discontinue treatment because of severe esophagitis and one of these died of complications related to grade 4 esophagitis. However, keeping the same doses of chemotherapy and replacing hyperfractionation with a standard single-day fraction, weekly doses of CDDP and paclitaxel of 35 mg/m2 and 45 mg/m2 could be safely administered. Neutropenia was by far the most relevant hematologic toxicity and occurred in 33 of 141 weekly delivered courses, but it was of grade 4 in only four courses. Substantial pulmonary or neurologic toxicity was not observed in this study. Two complete responses (CRs) and 13 partial responses (PRs) were observed, for a 60% overall response rate (95% confidence interval [CI], 39% to 79%). The median survival time was 16 months, with a 66% 1-year survival probability. CONCLUSION: CDDP 35 mg/m2/wk and paclitaxel 45 mg/m2/wk can be safely administered with concurrent standard RT. The use of hyperfractionation is associated with a more frequent occurrence of severe esophagitis and requires a reduction of the CDDP dose to 30 mg/m2/ wk. Only future randomized trials will elucidate which of these two approaches (standard or hyperfractionated RT) is the better option to improve the outcome of patients with locally advanced NSCLC.

Adult↗
PubMed1997

Weekly paclitaxel/cisplatin with concurrent radiotherapy in patients with locally advanced non-small cell lung cancer: a phase I study.

We designed a phase I study to determine the maximum tolerated doses of weekly cisplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (doses escalated alternately) when given concurrently with standard or hyperfractionated radiotherapy (RT) and to define the nature of the dose-limiting toxicity. Chemotherapy-naive patients with locally advanced non-small cell lung cancer received weekly combination cisplatin/paclitaxel with concurrent local RT. Radiation therapy was initially given at the dose of 1.2 Gy twice daily x 5 d/wk x 5 weeks (total dose, 60 Gy). In the last two patient cohorts, the single daily dose was decreased to 2 Gy x 5 d/wk x 6 weeks. Overall, 25 patients were recruited into five different cohorts. Esophagitis was the main nonhematologic toxicity, occurring in 16 of 25 patients (64%; grade 3 or 4 in five). Neutropenia was the most prevalent hematologic toxicity, occurring in 33 of 141 weekly courses, but grade 4 neutropenia was seen in only four courses. Cisplatin/paclitaxel doses of 35 mg/m2/wk and 45 mg/m2/wk, respectively, were safe when standard RT was used, while the cisplatin dose had to be decreased to 30 mg/m2/wk in patients receiving bifractionation. Two complete and 13 partial responses were observed, for a 60% overall response rate (95% confidence interval, 39% to 79%). Median survival was 16 months, with a 66% 1-year actuarial probability. We thus conclude that the cisplatin/paclitaxel combination given weekly can be safely administered concurrent with both standard or hyperfractionated RT. Hyperfractionation is associated with a higher incidence of severe esophagitis and required a slight reduction in cisplatin dose. To verify whether the use of a daily schedule translates into a better therapeutic index, a new phase I study is under way, testing twice-daily cisplatin/paclitaxel concurrently with hyperfractionated RT.

Adult↗
PubMed1995

Gunshot injuries of the liver: the Baragwanath experience.

BACKGROUND: This study comprised 304 patients with gunshot injuries of the liver, many of which from high-velocity firearms. The purpose of this study is to evaluate our management policy in gunshot injuries of the liver in light of our recent wider experience. METHODS: All grade I and II injuries and most grade III injuries were managed by simple operative measures, without postoperative mortality directly related to the liver trauma. RESULTS: Grade III, IV, and V injuries had 8.5%, 52%, and 16% resectional debridement rates and 8.5%, 38%, and 84% perihepatic packing rates, respectively. In the resectional debridement group the postoperative mortality rate was 15% (half the deaths were directly caused by the hepatic injury). The postoperative mortality rate in the perihepatic packing group was 31.5% of which 45% of deaths were due to ongoing bleeding, 27.5% to sepsis, and 27.5% to associated trauma. The septic complications were less common when packs were removed early. CONCLUSIONS: We suggest that resectional debridement and perihepatic packing should be liberally applied in the most severe grade III, most grade IV, and grade V gunshot injuries of the liver and that perihepatic packing should be removed as early as the physiologic derangements are corrected. Our experience with grade VI injuries is very limited, and their management should be studied in larger series.

Adolescent↗
PubMed1995

Health indicators and the organization of health care systems in western Europe.

OBJECTIVES: This study investigated the association between health care systems and health indicators in developed countries. METHODS: Cross-national comparisons were conducted with regression analysis between 17 Western European countries with two types of health care systems: national health services and social security systems. RESULTS: Health care expenditures were inversely correlated to potential years of life lost to females and to infant mortality rates; they were positively correlated to life expectancy for females. Regression models predicted that countries with national health services systems would have lower infant mortality rates at similar levels of gross domestic product (GDP) and health care expenditures. Finally, increases in health care expenditures would decrease the ratio of observed to predicted infant mortality rates according to GDP; this decrease would be greater in countries with national health services than in those with social security systems. The model predicted this difference to be about 13% at average levels of health expenditures. CONCLUSIONS: National health services seem to be more efficient at producing lower infant mortality rates than social security systems in Western European countries.

Developed Countries↗
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↗
PubMed1994

Combination of vinorelbine, cisplatin, and etoposide in advanced non-small cell lung carcinoma: a pilot study.

The combination of vinorelbine (VNR), cisplatin (CDDP) and etoposide (VP16) was reported to obtain major responses in more than 40% of patients with advanced non-small cell lung carcinoma (NSCLC). However, optimal dosages and schedule of the three drugs has remained unsettled. This trial was carried out to further assess the activity and toxicity of this regimen. We treated 19 patients (all males) affected by NSCLC, with a median age of 62 years and a median ECOG performance status of 1. Eleven of them had locally advanced disease and 8 showed distant metastases. The dose of CDDP was 30 mg/m2 i.v., while VP16 was given at 80 mg/m2 i.v. Both drugs were administered for 3 consecutive days every 3 weeks. The first 7 patients also received VNR 25 mg/m2 i.v. on days 1 and 8, while in the subsequent 12 cases VNR was administered at 30 mg/m2 i.v. on day 1. An overall activity of 42% (95% confidence limits, 20%-66%) was observed among treated patients, with no significant differences related to stage or histology. The dose limiting toxicity was essentially a grade 3-4 neutropenia occurring during treatment in 50% of patients, regardless of schedule employed. The actual median dose intensity of VNR was 13 mg/m2/wk (78% of the planned one) in the first 7 patients, and 9 mg/m2/wk (90% of the ideal one) in the following 12 patients. Though eight patients are still alive from 18+ to 29+ weeks at the time of this analysis, the overall median survival time was only 25 weeks. Our results support the high activity of this three-drug regimen in advanced NSCLC. However, the actual impact of this treatment on survival of patients should be defined with randomized trials.

Aged↗
PubMed1993

Immunological and clinical effects of intramuscular rIFN alpha-2a and low dose subcutaneous rIL-2 in patients with advanced malignant melanoma.

Fifteen patients with tumour recurrence following radical surgical excision of malignant melanoma were treated with a combination of interferon alpha-2a (rIFN alpha-2a) and interleukin-2 (rIL-2). Immunological monitoring (performed prior to therapy and on days 7, 21, and 28, of each course of treatment) showed significant changes of several parameters after rIFN alpha-2a and rIL-2 administration. A significant increase in cells expressing CD16 (cells bearing Fc receptor), CD25 (cells bearing IL-2 receptor), and CD56 (NK cells, activated lymphocytes), as well in levels of soluble IL-2 receptor, beta 2-microglobulin and neopterin was observed. Immunological changes were closely related to the injection of the biological agent and were more relevant during the first than the second cycle of treatment. rIFN alpha-2a and rIL-2 exerted a clear synergistic activity on the same immunological parameters. No major response was seen with the present approach: four subjects showed rapid progression of decrease during the first month of therapy, while of 11 patients who completed two courses of treatment, only five were considered in stable disease. In conclusion, our results suggest that a combination of rIFN alpha-2a and rIL-2, at dosages and schedules, used in this trial, was well-tolerated and immunologically active, but was clinically ineffective in the management of advanced melanoma.

Adult↗
PubMed1991

Treatment of advanced colorectal cancer with mitoxantrone, high dose folinic acid and fluorouracil.

A new combination chemotherapy including mitoxantrone 10 mg/m2 i.v. on day 1 and 5-fluorouracil 400 mg/m2 i.v. plus folinic acid 200 mg/m2 i.v. on days 1-5 was administered every 28 days to 13 patients with locally advanced or metastatic colon (1 case), ractosigmoid colon (4 cases), or rectum (8 cases) carcinoma. The median number of cycles performed was 3 (range, 1-9). No patient achieved complete or partial remission with this regimen, whereas 5 showed a stable disease lasting 3-8 months. Acute toxicity was mild/moderate in intensity and comparable to that reported with the standard 5-fluorouracil + folinic acid combination. Since we observed no major responses in our 13 consecutive patients, we consider that the overall activity of our regimen, at the doses and schedule utilized, was only moderately effective in advanced colorectal carcinoma.

Adult↗