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Biomedical subjects

Albert Font

Publications and source records attributed to Albert Font.

9 recordsLinked to original sources

Non-Cancer Causes of Death in Patients With Metastatic Hormone-Sensitive Prostate Cancer: A Real-World Analysis.

BACKGROUND: As overall survival improves in metastatic hormone-sensitive prostate cancer (mHSPC), non-cancer causes of death are increasingly relevant. METHODS: We conducted a real-world multicenter study of patients diagnosed with mHSPC treated with ADT alone or in combination. Causes of death before progression to castration-resistant prostate cancer (CRPC) were classified as cancer- or non-cancer-related. Deaths were classified as non-cancer-related if they occurred in the absence of cancer progression. RESULTS: Among 565 patients, 35 (6.2%) died from non-cancer-related causes without disease progression, mainly infections (34%) and cardiovascular events (20%). CONCLUSIONS: Non-cancer mortality represents a meaningful proportion of deaths in mHSPC, supporting systematic cardiovascular risk evaluation and infection-prevention strategies.

Humans↗

Feasiblity study of gemcitabine and cisplatin administered every two weeks in patients with advanced urothelial tumors and impaired renal function.

OBJECTIVES: Cisplatin-based combination chemotherapy is the mainstay of treatment for advanced bladder cancer. However, full doses of cisplatin cannot be delivered in patients with impaired renal function. Our aim was to prove the feasibility of a gemcitabine and low-dose cisplatin regimen, delivered every two weeks in patients with impaired renal function. MATERIAL AND METHODS: Patients with locally advanced or metastatic bladder cancer with creatinine clearance between 35-60 ml/min received gemcitabine 2500 mg/m2 and cisplatin 35 mg/m2 on day 1, every 14 days. RESULTS: Between January 2004 and March 2005, 17 patients were treated. Mean creatinine clearance was 47.8 ml/min (range: 37-59 ml/min). Four patients had previously received chemotherapy with gemcitabine and/ or platinum. Median number of cycles per patient was 5 (1-13). No patient developed renal toxicity or worsening of renal function. Main toxicities were (grade 3/4): Anemia 2/1; leucopenia: 1/2; trombopenia 1/1. There was one toxic death related to metabolic acidosis, secondary to vomiting. Among 16 patients evaluable for response, we observed one complete response, 7 partial responses (ORR: 53.3%; IC 95%: 28.1-78.5%), 6 stabilizations (37.5%) and 2 progressions (12.5%). CONCLUSIONS: Gemcitabine and low-dose cisplatin is a safe and feasible combination in patients with poor renal function. Response rates seem similar to those previously described with standard schedules of this combination.

Aged↗

Her-2/neu expression in prostate cancer: a dynamic process?

The clinical effects of targeting Her-2/neu in prostate carcinoma are not known. This study explores the feasibility of molecular profiling to determine the correlation between Her-2/neu expression and hormonal sensitivity. Patients with progressive androgen-independent prostate carcinoma were eligible to participate in the study. Her-2/neu expression was assessed on pretreatment tissue specimens and on bone marrow obtained in progressive androgen-independent disease. Her-2/neu expression was evaluated by immunohistochemistry and by fluorescence in situ hybridization in a consecutive series of 26 progressive androgen-independent prostate cancer patients. Twenty four bone marrow biopsy specimens and 16 prostate biopsies from 26 patients were analyzed. These biopsies were categorized by androgen sensitivity at the time of the biopsy. In total, 90% of specimens from bone marrow were Her-2/neu positive, and 10% of the specimens were Her-2/neu negative. Of the prostate biopsies, all were from patients with androgen-dependent disease. Three of 13 androgen-dependent prostate biopsies (23%) overexpressed Her-2/neu. Of the 10 tumor samples analyzed by fluorescence in situ hybridization, genomic amplification of the Her-2/neu locus was not detected in any of the metastatic prostate tumors. Her-2/neu expression varies with the clinical state of patients with prostate carcinoma: Accurate Her-2/neu profiling requires sampling metastatic tissue in patients with metastatic disease. Her-2/neu sampling from metastatic prostate carcinoma is not feasible until more reliable and practical methods can be developed.

Aged↗

Prospective randomized phase III trial of etoposide/cisplatin versus high-dose epirubicin/cisplatin in small-cell lung cancer.

High-dose epirubicin plus cisplatin was compared with the reference regimen of etoposide/cisplatin in small-cell lung cancer (SCLC). Four hundred two previously untreated patients with SCLC were randomized to receive etoposide 100 mg/m(2) on days 1-3 and cisplatin 100 mg/m(2) on day 1 or epirubicin 100 mg/m(2) and cisplatin 100 mg/m(2) on day 1 every 21 days for a total of 6 cycles. Patients were stratified according to treatment center and extent of disease (limited disease, n = 207; extensive disease, n = 195). Patients with limited disease were treated with thoracic radiation therapy after completion of chemotherapy, and those who exhibited a complete response were advised to receive prophylactic cranial irradiation. The primary endpoint was survival, and secondary endpoints were time to progression (TTP), response, toxicity, and costs. Patient characteristics were generally well balanced in the 2 arms, even though more patients in the epirubicin/cisplatin arm had > 5% weight loss and poor Karnofsky performance index compared with the etoposide/cisplatin arm. One hundred thirty-four patients (66.3%) in the etoposide/cisplatin arm and 126 (63.0%) in the epirubicin/cisplatin arm received all 6 planned cycles of chemotherapy. Response rate, TTP, and survival did not differ significantly between the 2 arms. Grade 3/4 neutropenia and toxic deaths occurred more frequently in the etoposide/cisplatin arm. Epirubicin/cisplatin showed a similar activity with a slightly lower toxicity profile than the reference regimen of etoposide/cisplatin. The epirubicin/cisplatin regimen may be recommended in the treatment of SCLC.

Adult↗

Gemcitabine and carboplatin in advanced transitional cell carcinoma of the urinary tract: an alternative therapy.

BACKGROUND: Cisplatin-based combinations are considered to be the standard treatment for advanced transitional cell carcinoma (TCC) of the urothelium. Many of the patients are elderly with concomitant diseases or impaired renal function. We studied the tolerance and activity of the gemcitabine/carboplatin combination as a therapeutic alternative. METHODS: Patients with locally advanced or metastatic TCC of the urothelium were treated with gemcitabine 1000 mg/m(2) on Days 1 and 8 and carboplatin area under the concentration-time curve 5 on Day 1 every 21 days. Patients with creatinine clearance of 30 mL/min or above and Karnofsky performance status (KPS) scores 60 or above were enrolled. RESULTS: A total of 227 cycles were administered to 41 patients, with an average of 5.5 cycles per patient (range, 1-8 cycles). Creatinine clearance was below 60 mL/min in 54% of patients, KPS was 70 or below in 37% of patients, and 37% of patients were 70 years old or older. Hematologic toxicity was mainly Grade 3/4 neutropenia in 63%, Grade 3/4 thrombocytopenia in 32%, and Grade 3/4 anemia in 54% of patients. There were only three episodes of febrile neutropenia and one death from neutropenic sepsis. Nonhematologic toxicity was mild, with asthenia as the most frequently reported event. We obtained 6 complete and 17 partial responses, for an overall response rate of 56.1% (95% confidence interval [CI], 40.6-71.6%). Progression-free survival was 7.2 months (95% CI, 5.7-8.5) and median survival was 10.1 months (95% CI, 8.8-12.2). CONCLUSIONS: The combination of gemcitabine plus carboplatin achieves a similar result to doublets using cisplatin. It has an acceptable toxicity profile and enables patients with impaired renal function and/or poor performance status and elderly patients to be treated.

Aged↗

Weekly regimen of irinotecan/docetaxel in previously treated non-small cell lung cancer patients and correlation with uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) polymorphism.

PURPOSE: Inherited variations in drug metabolizing enzymes may influence drug efficacy. This phase II study assesses the impact of second-line weekly irinotecan (CPT-11)/docetaxel in non-small cell lung cancer (NSCLC) patients, and gauges the uridine diphosphate glucuronosyl transferase (UGT1A1) polymorphism influence in toxicity and antitumor activity. EXPERIMENTAL DESIGN: Fifty-one patients with NSCLC treated with at least one prior chemotherapy regimen were enrolled. Patients received irinotecan 70 mg/m(2) followed by docetaxel 25 mg/m(2). Both drugs were given on days 1, 8, and 15 every 28 days. UGT1A1 polymorphism were analyzed in blood samples of 47 patients. The UGT1A1 polymorphism are classified according to the number of TA repeats in the promoter region of this gene. RESULTS: Three patients (6%) achieved a partial response and nineteen patients (37%) had stable disease. Median survival was 8 months (95% CI: 4.8-11.2) and 1-year survival 30%. Grade 3-4 hematologic toxicity was low (less than 10% of patients); 15% of patients had grade 3 asthenia and 25% of patients had grade 3/4 diarrhea. The frequency of UGT1A1 genotypes was as follows: 6/6 49%, 6/7 36%, and 7/7 15%. No differences in toxicity were observed according to UGT1A1 polymorphism. A nonsignificant improvement in time to progression (4 vs. 3 months) and median survival (11 vs. 8 months) was detected in patients with the variant alleles (6/7 and 7/7). CONCLUSIONS: This weekly irinotecan/docetaxel regimen has shown an acceptable toxicity profile while encouraging median and 1-year survival in heavily pretreated NSCLC patients. The tendency to better prognosis in patients carrying the variant genotypes 6/7 and 7/7 of UGT1A1 gene requires further validation.

Adult↗

Double-blind, placebo-controlled, randomized phase III trial of darbepoetin alfa in lung cancer patients receiving chemotherapy.

BACKGROUND: Patients receiving chemotherapy often develop anemia. Darbepoetin alfa (Aranesp(TM)) is an erythropoiesis-stimulating glycoprotein that has been shown, in dose-finding studies, to be safe and clinically active when administered to patients with cancer every 1, 2, or 3 weeks. This phase III study compared the safety and efficacy of darbepoetin alfa with placebo in patients with lung cancer receiving chemotherapy. METHODS: In this multicenter, double-blind, placebo-controlled study, 320 anemic patients (hemoglobin or=25% improvement; mean difference = 13%; 95% CI = 2% to 23%, P =.019) than patients receiving placebo. Patients receiving darbepoetin alfa did not appear to have any untoward effect in disease outcome and did not develop antibodies to the drug. Adverse events were similar between the groups. CONCLUSIONS: Patients with chemotherapy-associated anemia can safely and effectively be treated with weekly darbepoetin alfa therapy. Darbepoetin alfa decreased blood transfusion requirements, increased hemoglobin concentration, and decreased fatigue. Although no conclusions can be drawn about survival from this study, the potential salutary effect on disease outcome warrants further investigation in a prospectively designed study.

Adult↗

Phase II non-randomized study of three different sequences of docetaxel and vinorelbine in patients with advanced non-small cell lung cancer.

Docetaxel and vinorelbine as single agents and in combination with cisplatin have shown significant activity in advanced non-small cell lung cancer (NSCLC). Significant neutropenia has been observed with the combination of docetaxel/vinorelbine. To gain insight into the potential synergism of this combination, we examined three different sequences of docetaxel 75 and vinorelbine 20 mg/m(2), every 3 weeks, in locally advanced and metastatic NSCLC patients. About 14 patients were evaluable in each schedule: schedule A, docetaxel day 1, vinorelbine days 1 and 6; schedule B, docetaxel day 6, vinorelbine days 1 and 6; schedule C, docetaxel day 1, vinorelbine days 6 and 15. Response rates were: 42.8, 7.1 and 21.4% for schedules A, B and C, respectively (P=0.01, schedule A vs. B). Median survival time was 16, 6.5 and 10.6 months for schedules A, B and C, respectively (P=0.04, schedule A vs. B). Neutropenia was the commonest toxicity; 43% of patients in schedule A and 57% of patients in schedule B had a febrile neutropenia episode. Prophylactic granulocyte-colony stimulating factor (G-CSF) was prescribed in schedule C after the first episode of febrile neutropenia. Non-hematologic toxicities were mild in all three schedules. For future studies, schedule A with lower doses is recommended.

Adult↗

Phase II study of gemcitabine and cisplatin in chemonaive patients with advanced epithelial ovarian cancer.

This phase II study evaluated the activity of gemcitabine (Gemzar) plus cisplatin (Platinol) as first-line treatment of advanced epithelial ovarian cancer. Forty-two chemonaive patients with advanced (stage III and IV) epithelial ovarian cancer received gemcitabine 1,250 mg/m(2) on days 1 and 8 and cisplatin 100 mg/m(2) on day 1, every 3 weeks, up to eight cycles. The median number of cycles completed was 5 (range 2-8). Of the 41 patients evaluable for tumor response, 20 had a partial response and nine had a complete response, for an overall clinical and pathologic response rate of 70.7% (95% CI 56.8-84.6%). Median overall survival for all 42 patients was 23.4 months (95% CI 15.9-29.9 months) and the median progression-free survival time was 10.4 months (95% CI 9.4-13.5 months). The combination was generally manageable. Hematologic toxicity (grade 3/4 neutropenia: 31.0/21.4%; grade 3/4 thrombocytopenia: 9.5/4.8%; grade 3/4 anemia: 11.9/0%) and nausea and vomiting (grade 3/4: 35.7/31.0%) were the most common toxicities. There was one toxic death (septic shock due to hematologic toxicity-induced infection). We conclude that gemcitabine plus cisplatin is active and feasible as first-line treatment of advanced epithelial ovarian cancer. Further clinical trials with the addition of gemcitabine to first-line treatment appear warranted.

Adult↗