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Biomedical subjects

D Castellano

Publications and source records attributed to D Castellano.

15 recordsLinked to original sources
PubMed2022

Lurbinectedin, a selective inhibitor of oncogenic transcription, in patients with pretreated germline BRCA1/2 metastatic breast cancer: results from a phase II basket study.

BACKGROUND: Lurbinectedin, a selective inhibitor of oncogenic transcription, has shown preclinical antitumor activity against homologous recombination repair-deficient models and preliminary clinical activity in BRCA1/2 breast cancer. PATIENTS AND METHODS: This phase II basket multitumor trial (NCT02454972) evaluated lurbinectedin 3.2 mg/m2 1-h intravenous infusion every 3 weeks in a cohort of 21 patients with pretreated germline BRCA1/2 breast cancer. Patients with any hormone receptor and human epidermal growth factor receptor 2 status were enrolled. The primary efficacy endpoint was overall response rate (ORR) according to RECIST v1.1. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. RESULTS: Confirmed partial response (PR) was observed in six patients [ORR = 28.6%; 95% confidence interval (CI) 11.3% to 52.2%] who had received a median of two prior advanced chemotherapy lines. Lurbinectedin was active in both BRCA mutations: four PRs in 11 patients (36.4%) with BRCA2 and two PRs in 10 patients (20.0%) with BRCA1. Median DoR was 8.6 months, median PFS was 4.1 months and median OS was 16.1 months. Stable disease (SD) was observed in 10 patients (47.6%), including 3 with unconfirmed response in a subsequent tumor assessment [ORR unconfirmed = 42.9% (95% CI 21.8% to 66.0%)]. Clinical benefit rate (PR + SD ≥ 4 months) was 76.2% (95% CI 52.8% to 91.8%). No objective response was observed among patients who had received prior poly (ADP-ribose) polymerase inhibitors. The most common treatment-related adverse events (AEs) were nausea (61.9%), fatigue (38.1%) and vomiting (23.8%). These AEs were mostly grade 1/2. The most common grade 3/4 toxicity was neutropenia (42.9%: grade 4, 23.8%: with no febrile neutropenia). CONCLUSIONS: This phase II study met its primary endpoint and showed activity of lurbinectedin in germline BRCA1/2 breast cancer. Lurbinectedin showed a predictable and manageable safety profile. Considering the exploratory aim of this trial as well as previous results in other phase II studies, further development of lurbinectedin in this indication is warranted.

Humans↗
PubMed2006

Randomized study of cefepime versus ceftazidime plus amikacin in patients with solid tumors treated with high dose chemotherapy (HDC) and peripheral blood stem cell support (PBSCS) with febrile neutropenia.

OBJECTIVE: This randomized clinical trial evaluated the efficacy and safety of monotherapy with cefepime for patients with solid tumors treated with high dose chemotherapy (HDC) and peripheral blood stem cell support (PBSCS) with febrile neutropenia. SUBJECTS: Patients with solid tumors treated with HDC and PBSCS, that developed fever and neutropenia (absolute neutrophil count < 500 cells/microL) were eligible, and randomly assigned to receive ceftazidime plus amikacin or cefepime. RESULTS: Fifty-one episodes were randomized, and all were evaluable (27 received ceftazidime plus amikacin arm, and 24 cefepime). Major efficacy endpoints did not show significant differences, with success rates of 44.4% and 54.2% (p = 0.481) for the combination arm and the monotherapy arm, respectively. The proportion of patients that became afebrile in the first 24 hours was significantly higher in the cefepime group (41.7% vs 11.1%, respectively; p = 0.012). However, due to its premature closure and small sample size, this study lacks the adequate power to definitely address this question. CONCLUSIONS: Cefepime monotherapy appeared to have an equivalent efficacy and safety as empiric treatment in febrile neutropenia episodes in a highrisk population compared with ceftazidime and amikacin. Nevertheless, this study is not adequately powered to answer this question. Given the small number of patients randomized and the single-center nature of this study, these results must be cautiously interpreted.

Adult↗
PubMed2003

Biweekly vinorelbine and gemcitabine: a phase I dose-finding study in patients with advanced solid tumors.

BACKGROUND: The purpose of this study was to determine the dose-limiting toxicity (DLT) and maximum tolerated dose of a combination of vinorelbine plus gemcitabine administered on a biweekly schedule in patients with advanced solid tumors. PATIENTS AND METHODS: Patients with advanced or refractory solid tumors included in this phase I study were treated with vinorelbine followed by gemcitabine. Vinorelbine was given intravenously over 10 min, and gemcitabine was given intravenously at an fixed-dose infusion rate of 10 mg/m(2)/min. Six dose levels of vinorelbine/gemcitabine were explored: 20/2000, 25/2500, 25/3000, 30/3000, 30/3500 and 30/2500 mg/m(2). RESULTS: Nineteen patients were included in the study. Fourteen patients were pretreated with chemotherapy and/or radiotherapy. A total of 123 cycles of chemotherapy were administered. DLTs were neutropenic fever and grade 3 asthenia at dose level 5 (30/3500 mg/m(2)); at dose level 4 (30/3000 mg/m(2)) they were grade 3 asthenia, and a radiation-recall reaction and pneumonitis. Sixteen patients were evaluable for efficacy. Five patients had an objective response (one complete response and four partial responses), for an overall response rate of 31%. CONCLUSIONS: The recommended dose for phase II study is vinorelbine 30 mg/m(2) and gemcitabine 2500 mg/m(2) administered once every 2 weeks. This regimen is feasible and well-tolerated at this dose, and shows a good clinical activity in all levels explored.

Aged↗
PubMed2002

Induction chemotherapy with paclitaxel, cisplatin and 5-fluorouracil for squamous cell carcinoma of the head and neck: long-term results of a phase II trial.

BACKGROUND: The aim of this study was to evaluate the efficacy and toxicity of a combination of paclitaxel, cisplatin and 5-fluorouracil (PPF) as induction chemotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). METHODS: Seventy patients with previously untreated stage III-IV SCCHN were included in this phase II trial. Induction treatment consisted of a maximum of three outpatient courses of paclitaxel 175 mg/m(2) as a 3-h infusion on day 1, cisplatin 100 mg/m(2) on day 2, and 5-fluorouracil (5-FU) 500-750 mg/m(2)/day as a 24-h continuous infusion on days 2-6, repeated every 3 weeks. The 5-FU dose was reduced from 750 mg/m(2)/day to 500 mg/m(2)/day due to the excessive toxicity observed in the first 14 patients enrolled. Local treatment consisted of radiotherapy and/or surgery. RESULTS: Two-hundred-and-one cycles were administered to 70 patients. The main toxicities of PPF were neutropenia (grade 4, 14%; febrile neutropenia, 4%), peripheral neuropathy (grade 2-3, 14%) and catheter-associated venous thrombosis (7%). There were three early deaths (two from neutropenic sepsis and one from pulmonary embolism), and 13 patients required hospitalization due to toxicity. Other side effects included mucositis, anorexia, diarrhea, myalgias and alopecia. The overall response rate to PPF was 88%, including 59% complete responses (CR) and 29% partial responses. The CR rates at the primary tumor and neck lymph nodes were 74% and 62%, respectively. With a median follow-up of 51 months (range 40-63 months), the estimated 5-year time-to-disease progression and overall survival rates were 56% and 44%, respectively. CONCLUSIONS: The PPF regimen has major antitumor activity and is associated with manageable toxicity as induction treatment in SCCHN patients. The high complete response rate and favorable long-term outcome justify further evaluation of this chemotherapy combination.

Adult↗
PubMed2000

Dehydrozaluzanin C: a potent plant growth regulator with potential use as a natural herbicide template.

The natural product dehydrozaluzanin C (former DHZ) is a sesquiterpene lactone obtained from different weeds of the Compositae family. Its potential as a plant growth regulator has been evaluated by using a phytotoxic allelopathic bioassay, where the commercial herbicide Logran is used as internal reference. The evaluation is made based on their effects on germination and growth over several dicotyledon and monocotyledon species. The activity was tested in the range of 1000-0.001 microM. In almost all cases, DHZ was more active than the internal reference at 1000 microM, and its activity fell below the level of the internal reference at 100 microM. These results confirm DHZ as a potent plant growth regulator and a good candidate for the development of new herbicide models.

Herbicides↗
PubMed2000

Sesquiterpene lactones with potential use as natural herbicide models. 2. guaianolides.

A structure-activity study to evaluate the effect of 17 guaianolide sesquiterpene lactones (in a range of 100-0.001 microM) on the growth and germination of several mono- and dicotyledon target species is accomplished. Results are compared with those obtained in the same bioassay with an internal standard, the commercial herbicide Logran, to validate the results with a known active formulation and to compare the results with a commercial product to test their potential use as natural herbicide models. Specific conditions for the selective mono- or polyhydroxylation of guaianolides using the SeO(2)/tert-butyl hydroperoxide system are presented and discussed. The high regio- and stereoselectivities of the reaction are explained through the specific structural requirements of the bulky first adduct formed during the ene reaction. These compounds appear to have deeper effects on the growth of either monocots or dicots than the previously tested germacranolides. Otherwise, the lactone group seems to be necessary for the activity, though it does not necessarily need to be unsaturated. However, the presence of a second and easily accessible unsaturated carbonyl system greatly enhances the inhibitory activity. Lipophilicity and the stereochemistry of the possible anchoring sites are also crucial factors for the activity. Finally, the levels of growth inhibition obtained with some compounds on dicots or monocots are totally comparable to those of Logran and allow proposing them as lead compounds.

Herbicides↗
PubMed2000

Search for a standard phytotoxic bioassay for allelochemicals. Selection of standard target species.

In the search for a standard bioassay of phytotoxicity for allelochemicals, 22 commercial varieties of eight plant species [four dicotyledons: lettuce (Compositae), carrot (Umbelliferae), cress (Cruciferae), tomato (Solanaceae); and four monocotyledons: onion (Liliaceae), barley, wheat, and corn (Gramineae)] proposed as models for the most common weed families have been tested at different pH and solution volumes per set conditions. Nine commercial varieties selected as standard target species (STS) were tested with standard commercial herbicides to ensure their sensitivity to phytotoxic compounds. Results are discussed to establish the proper growth requirements, and sensitivity of commercial seeds of STS and to find the most suitable commercial herbicides that allow comparison with an internal standard to validate the response of potential allelochemicals.

Biological Assay↗
PubMed1999

Sesquiterpene lactones with potential use as natural herbicide models (I): trans,trans-germacranolides.

A structure-activity study to evaluate the effect of the trans, trans-germacranolide sesquiterpene lactones costunolide, parthenolide, and their 1,10-epoxy and 11,13-dihydro derivatives (in a range of 100-0.001 microM) on the growth and germination of several mono and dicotyledon target species is accomplished. Results are compared with those obtained in the same bioassay with an internal standard, the commercial herbicide Logran, to validate the results with a known active formulation and to compare the results with a commercial product to test their potential use as natural herbicide models. These compounds appear to have a more selective effects on the radicle growth of monocotyledons. Certain factors such as the presence of nucleophile-acceptor groups and their accessibility enhance the inhibitory activity. The levels of radicle inhibition obtained with some compounds on wheat are totally comparable to those of Logran and allow to propose them as lead compounds.

Herbicides↗
PubMed1999

Phase I-II study of gemcitabine and fluorouracil as a continuous infusion in patients with pancreatic cancer.

PURPOSE: To determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and efficacy of gemcitabine combined with fluorouracil (5-FU) in patients with pancreatic cancer. PATIENTS AND METHODS: Patients with measurable, locally advanced, nonresectable or metastatic pancreatic cancer were candidates for the study. 5-FU was given via protracted venous infusion (PVI) at a fixed dosage of 200 mg/m2/d, and gemcitabine was administered weekly for 3 consecutive weeks every 4 weeks. The initial dose of gemcitabine was 700 mg/m2 and was escalated in increments of 100 mg/m2/wk until the appearance of severe toxicity. Measurements of efficacy included the following: response rate; clinical benefit response, which is a composite measurement of pain, performance status, and weight loss; time to disease progression; and survival. RESULTS: Twenty-six patients received a total of 109 courses. Dose-limiting toxicity, which consisted of grade 4 neutropenia with fever (one patient) and grade 4 thrombocytopenia (one patient), was observed in two of three patients treated with 1,100 mg/m2/wk of gemcitabine. On the basis of these results, the MTD of gemcitabine with 5-FU via PVI on this schedule was 1,000 mg/m2. Sixteen patients developed grade 3-4 neutropenia, and three patients developed grade 3-4 thrombocytopenia. Grade 3-4 nonhematologic toxicity consisted of diarrhea (two patients) and cutaneous toxicity, asthenia, edema, mucositis, and nausea and vomiting (one patient each). The delivered dose-intensity of gemcitabine was similar at the 1,000 mg/m2 dose level (599 mg/m2/wk) as at the 900 mg/m2 (601 mg/m2/wk) dose level. For this reason, the recommended dose of gemcitabine for phase II evaluation on this schedule was 900 mg/m2. Five patients had objective responses (one complete response and four partial responses; response rate, 19.2%; 95% confidence interval [CI], 6.5 to 39.3), and 10 patients had improvement of disease-related symptoms (45%; 95% CI, 24 to 67). After a median follow-up of 17.7 months (range, 7.8 to 24.8 months), the median progression-free survival and overall survival times were 7.4 months (95% CI, 3.3 to 11.4) and 10.3 months (95% CI, 8.1 to 12.5), respectively. CONCLUSION: The MTD of gemcitabine when combined with 5-FU via PVI on this schedule was 1,000 mg/m2/ wk; however, on the basis of administered dose-intensity, the recommended dose for additional investigation is 900 mg/m2. This combination chemotherapy regimen was well tolerated and showed promising antitumor activity in the treatment of pancreatic cancer.

Adult↗
PubMed1998

A multicenter randomized Phase II trial of granulocyte-colony stimulating factor-supported, platinum-based chemotherapy with flexible midcycle cisplatin administration in patients with advanced ovarian carcinoma. PSAMOMA Cooperative Group, Spain.

BACKGROUND: The purpose of this study was to analyze whether the addition of granulocyte-colony stimulating factor (G-CSF) to platinum-based combination chemotherapy could increase platinum dose intensity and response rates and decrease hematologic toxicity in patients with advanced epithelial ovarian carcinoma. METHODS: Patients with untreated advanced ovarian carcinoma (International Federation of Gynecology and Obstetrics [FIGO] Stage IIC-IV) were treated after maximum debulking surgery with cyclophosphamide, 750 mg/m2, and carboplatin, 350 mg/m2, on Day 1 plus cisplatin, 75 mg/m2, on Day 14 when clinically indicated (adequate bone marrow and renal function). Patients were randomized to receive chemotherapy alone (Arm A) or chemotherapy supported with G-CSF (5 microg/kg subcutaneously on Days 2-13; Arm B). RESULTS: Between November 1993 and April 1995, 80 patients were included. Seventy-eight patients were evaluable for dose intensity calculations. Both groups were well matched with regard to age, Eastern Cooperative Oncology Group performance status, histopathologic subtype, tumor grade, FIGO stage, and residual tumor after surgery. The dose intensities calculated in mg/m2/week for cyclophosphamide and carboplatin were similar in both groups; however, the dose intensity of cisplatin was higher in Arm B (5.7 mg/m2 vs. 10.3 mg/m2). The occurrence of Common Toxicity Criteria Grade 3-4 neutropenia was less common in the G-CSF arm (55% vs. 7.7%). Response rates (52% vs. 68%) and pathologic complete responses (32% vs. 25%) were similar in both groups. CONCLUSIONS; The addition of G-CSF to this platinum-based chemotherapy regimen in patients with advanced ovarian carcinoma resulted in a modest increment in platinum dose intensity and appeared to reduce the incidence of Grade 3-4 neutropenia.

Adult↗
PubMed1998

A phase II study of a novel gemcitabine plus cisplatin regimen administered every three weeks for advanced non-small-cell lung cancer.

BACKGROUND: The aim of this study was to determine the clinical activity and toxicity of a novel chemotherapy combination regimen of gemcitabine plus cisplatin, administered every three weeks, in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Twenty-six previously untreated stages III (14) and IV (12) patients were included. Gemcitabine was administered on days 1 and 8 at a dose of 1250 mg/m2 and cisplatin was administered at a dose of 100 mg/m2 on day 1, every 21 days. RESULTS: Twenty-five patients were evaluable for response. One patient achieved a complete response, and 16 patients partial responses. The overall response rate was 65.3% (95% CI: 45%-82%). The main toxicity was hematological: neutropenia NCIC-CTC grade 3-4 in 54% of the patients, and thrombocytopenia grade 3-4 in 23%. The non-hematological toxicity was mild and tolerable. Only 13% of gemcitabine injections were dose-reduced or omitted due to toxicity. The actual dose-intensity of gemcitabine was 715 mg/m2/week, and 31 mg/m2/week for cisplatin. These figures represent the 86% and 93% of the theoretical dose intensity of both drugs, respectively. With a median follow-up of 10 months (range 7-13), 17 patients are still alive and nine have died. The median overall survival is 12 months. CONCLUSION: This novel combination of gemcitabine and cisplatin administered every three weeks is well tolerated and induces a remarkably high response rate. The regimen proves more interesting than the four-week schedules, particularly regarding patients who are candidates for local therapy.

Adult↗
PubMed1998

Phase II trial of cisplatin and gemcitabine in advanced squamous-cell carcinoma of the head and neck.

BACKGROUND: To evaluate the toxicity profile and efficacy of cisplatin combined with gemcitabine in patients with irresectable locally recurrent or metastatic squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: Gemcitabine was given at a dose of 800 mg/m2 on days 1, 8 and 15, plus cisplatin at a dose of 50 mg/m2 on days 1 and 8; every four weeks. RESULTS: Twenty-four patients with a median age of 59 years (range 42-74) were included. All patients were evaluable for toxicity and 22 patients were assessable for response. Eleven cases had advanced recurrent locoregional disease while 13 patients had metastatic disease. One CR (4.7%) and four PR (18%) were observed, for an overall response rate of 22.7% (95% CI: 8%-42%). The main toxicity was hematological: neutropenia grade 3-4 in 28% of the cycles and thrombocytopenia grade 3-4 in 16%. The most significant non-hematological toxicity was asthenia grade 2-3 in 24% of the cycles. CONCLUSIONS: This cisplatin plus gemcitabine combination schedule has a favourable toxicity profile with a discrete activity in patients with locally recurrent or metastatic squamous-cell carcinoma of the head and neck.

Adult↗
PubMed1998

A simple, cost-effective method for practicing phacoemulsification in the cadaveric eye.

The authors describe an inexpensive, reliable method for practicing intraocular surgery using a rigid contact lens as a temporary keratoprosthesis. This method allows clear visualization of the anterior chamber and lenticular structures for practicing modern cataract surgery, including capsulorhexis, hydrodissection, phacoemulsification, cortical aspiration, and intraocular lens insertion.

Cadaver↗