Recurrence of hepatitis C in liver transplants from elderly donors aged more than 75 years.
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Age Factors↗
Biomedical subjects
G Catalano
Publications and source records attributed to G Catalano.
Management of massive and persistent ascites and/or hydrothorax after liver transplantation.
PURPOSE: To describe the results of the treatment of eight liver transplantation (LT) patients subsequently developing large volumes of long-lasting ascites. PATIENTS AND METHODS: Between August 1996 and February 2003, 405 LTs were performed in 375 patients, eight (1.97%) of whom (six men and two women of mean age of 55.4 +/- 5.2 years) subsequently developed massive (> 500 mL/d) and persistent ascites and/or hydrothorax. All patients were HCV positive. The mean age of the liver donors was 66.8 +/- 21.9 years. All LTs were performed by replacement of the recipient retrohepatic vena cava. RESULTS: The eight patients displayed sinusoidal portal hypertension related to biopsy-proven recurrence of HCV infection. Mean wedged hepatic venous pressure was 14.9 +/- 5.1 mm Hg and mean portal vein/right atrial pressure gradient (PAPG) was 17.3 +/- 4.8 mm Hg. In two patients, the ascites appeared the day after LT; in the remaining six, ascites and/or hydrothorax appeared after 342.3 +/- 167.7 days. Seven patients with a mean PAPG of 18.4 +/- 3.9 mm Hg and a mean plasma/ascites albumin concentration gradient of 2.8 +/- 0.3 g/L were treated by means of a trans-jugular intrahepatic portosystemic shunt TIPS, and one (with a PAPG of 9 mm Hg and a plasma/ascites albumin concentration gradient of 1.38 g/L) by means of spleen arterial embolisation. After a mean follow-up of 558 +/- 147.2 days, the ascites and/or hydrothorax have resolved in five patients (62.5%), one (12.5%) has stable ascites not requiring paracentesis, and two (25%) have died of multiorgan failure. CONCLUSIONS: These data suggest the efficacy of the aggressive treatment of massive and persistent ascites and/or hydrothorax.
Ascites↗
Weekly gemcitabine and cisplatin chemotherapy: a well-tolerated but ineffective chemotherapeutic regimen in advanced pancreatic cancer patients. A report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD).
BACKGROUND: This phase II study was initiated to determine the activity and toxicity of a combination of gemcitabine (GEM) and cisplatin (CDDP) in patients with pancreatic cancer. PATIENTS AND METHODS: CDDP 35 mg/m(2) was given as a 30-min infusion and GEM 1000 mg/m(2) as a 30-min infusion. Both drugs were administered once weekly for 2 consecutive weeks out of every 3 weeks to chemonaive patients with locally advanced or metastatic pancreatic cancer. RESULTS: Forty-five advanced pancreatic cancer patients received this regimen for a total of 180 cycles of chemotherapy. One complete and four partial responses have been observed for an overall response rate of 9% (95% confidence interval 10% to 11%). Twenty-one patients (46%) had stable disease and 19 progressed on therapy. The median time to progression was 3.6 months, with a median survival of 5.6 months. A clinical benefit was obtained in nine of 37 patients (24%). Side-effects were mainly represented by hematological toxicity. Grade 3/4 WHO toxicities included neutropenia (6% of the patients) and thrombocytopenia (11%). The dose of GEM and CDDP was reduced in 14 patients (31%) and treatment was delayed in 10 patients (22%). CONCLUSIONS: Our results in terms of response rate, clinical benefit and survival do not support an advantage for the combination of GEM and CDDP given by this schedule.
Adult↗
Surgical complications after liver transplantation.
AIM: The number of liver transplantations in Italy has steadily increased over the last 10 years as a result of the use of donors aged more than 60 years. The use of organs with a reduced functional reserve has been compensated for by improvements in immunosuppressive therapy, surgical techniques and the management of postoperative complications. This article describes the incidence and treatment of the main surgical complications after liver transplantation. METHODS: Between January 1996 and June 2003, 398 patients received 430 transplants at our Centre. Thirty-seven early relaparotomies were performed (8.6%), including 12 retransplantation (2.8%). The 1-, 3- and 5-year actuarial survival of the patients was 79.8%, 72.2% and 67.5%, and that of the grafts was 75.9%, 68% and 63.4%. Perioperative mortality was 10.5% (with no intraoperative deaths). RESULTS: The overall incidence of biliary complications was 31.6%, 9.1% of which were due to the removal of the Kehr tube. There were 42 (9.8%) anastomotic stenoses, 5 (1.2%) extra-anastomotic stenoses, 1 (0.2%) anastomotic leak, 5 (1.2%) extra-anastomotic leaks, and 19 (4.4%) ischemic-type biliary lesions. The overall incidence of vascular complications was 6.9%: 7 (1.6%) cases of hepatic artery thrombosis, 17 (4.0%) arterial stenoses, 1 (0.2%) arterial pseudoaneurysm, 4 (0.9%) cases of portal thromboses and 1 (0.2%) case of caval laminar thrombosis. Eight patients (1.9%) developed massive and persistent post-transplant ascites and/or hydrothorax. CONCLUSION: The use of donors aged more than 60 years makes it possible to maintain high standards of patient and graft survival that is not only due to the optimisation of immunosuppressive protocols, but also to improvements in surgical techniques, intensive care and the management of surgical complications.
Adolescent↗
Oxaliplatin plus raltitrexed and leucovorin-modulated 5-fluorouracil i.v. bolus: a salvage regimen for colorectal cancer patients.
The aim of the present study was to define the activity and tolerability of a triplet regimen including oxaliplatin 130 mg x m(-2) (2 h i.v. infusion) and raltitrexed 3.0 mg x m(-2) (15 min i.v. infusion) given on day 1, followed by levo-folinic acid 250 mg x m(-2) (2 h i.v. infusion) and 5-fluorouracil 1050 mg x m(-2) i.v. bolus on day 2, every 2 weeks, in pretreated colorectal cancer patients. From April 1999 to December 2000, 50 patients were enrolled: 26 were males and 24 females, their median age was 63 (range, 43-79) years; ECOG performance status was 0 in 26 patients, > or =1 in 24 patients; 26 patients had received previous adjuvant chemotherapy, 40 patients had been exposed to one or two lines of palliative chemotherapy (including irinotecan in 31 cases); 18 patients were considered chemo-refractory. A total of 288 cycles were administered, with a median number of 6 (range 1-12) courses per patient. A complete response was obtained in three patients, and a partial response in nine patients, giving a major response rate of 24% (95% confidence interval, 13-38%), while 15 further patients showed a stable disease, for an overall control of tumour growth in 60% of patients. Three complete responses and three partial responses were obtained in patients pretreated with irinotecan (response rate, 19%); among refractory patients, three achieved partial responses (response rate, 13%). After a median follow-up of 18 (range, 10-30) months, 40 patients showed a progression of disease: the growth modulation index ranged between 0.2 and 2.5: it was > or =1.33 (showing a significant delay of tumour growth) in 16 (40%) patients. Actuarial median progression-free survival time was 7.6 months, and median survival time was 13.6 months: estimated probability of survival was 55% at 1 year. Main severe toxicity was neutropenia: World Health Organisation grade 4 affected 32% of patients; non-haematological toxicity was mild: World Health Organisation grade 3 diarrhoea was complained of by 8%, and grade 3 stomatitis by 4% of patients; neurotoxicity (according to Lévi scale) was scored as grade 3 in 8% of patients. In conclusion, this regimen was manageable and active as salvage treatment of advanced colorectal cancer patients; it showed incomplete cross-resistance with irinotecan-based treatments, and proved to delay the progression of disease in a relevant proportion of treated patients.
Adult↗
An analysis of p53, BAX and vascular endothelial growth factor expression in node-positive rectal cancer. Relationships with tumour recurrence and event-free survival of patients treated with adjuvant chemoradiation.
Tumours of patients with node-positive rectal cancer were studied by immunohistochemistry for p53, BAX and vascular endothelial growth factor expressions. Results were correlated to the relapse rate, the pattern of relapse and the event-free survival after radical surgery and adjuvant chemoradiation. After a median follow-up of 60 months, 39 patients remained disease-free and 40 patients relapsed (18 local relapses and 22 distant metastases). The majority of disease-free patients showed p53 negative and vascular endothelial growth factor negative tumours. Local relapses occurred more frequently in patients with p53 overexpressing tumours (P<0.01), while distant metastases were in patients with vascular endothelial growth factor positive tumours (P<0.003). Patients with p53 negative or vascular endothelial growth factor negative tumours showed better event-free survival than patients with p53 positive or vascular endothelial growth factor positive tumours. BAX analysis did not show any association with patients' outcome and it was unrelated to the p53 status. Adjuvant treatment strategies for node-positive rectal cancer may be improved by identifying categories of high-risk patients. In this study, vascular endothelial growth factor and p53 expressions correlated with recurrent disease, pattern of relapse and poor event-free survival.
Aged↗
Infusional 5-fluorouracil, cisplatin and mitomycin C in advanced gastric cancer: a low cost effective regimen.
Recently, we reported a highly active regimen in advanced gastric cancer including a weekly administration of cisplatin, epidoxorubicin, leucovorin, 5-fluorouracil with the support of filgrastim. In order to simplify the administration and to decrease the toxicity of these drugs, mainly epidoxorubicin-induced alopecia, we designed a regimen including an infusional 5-fluorouracil schedule according to the de Gramont regimen, cisplatin and mitomycin C replacing epidoxorubicin. Forty-five patients with advanced or metastatic gastric cancer were treated with cisplatin 50 mg m(-2) i.v. on day 1, every 2 weeks, 6S-stereoisomer-leucovorin 100 mg m(-2) i.v. followed by 5-fluorouracil 400 mg m(-2) i.v. bolus and 600 mg m(-2) i.v. in a 22-h infusion, on days 1 and 2, every 2 weeks, and mitomycin C 7 mg m(-2) i.v. bolus on day 2, every 6 weeks. Grades 3-4 toxicities (National Cancer Institute-Common Toxicity Criteria) consisted mainly of neutropenia and thrombocytopenia. Five patients had a complete response and 16 had a partial response for an overall response rate of 46.7% (95% confidence interval, 32.1-61.2%). The median survival was 11 months. The combination of cisplatin, 5-fluorouracil and leucovorin according to de Gramont, and mitomycin C seems to be an active and safe regimen in the treatment of advanced gastric cancer. Because of its low cost it may be suggested for patients not enrolled into clinical trials.
Adult↗
Cavoportal hemitransposition: patient selection criteria and outcome.
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Adult↗
Preclinical and phase I study of oxaliplatin and topotecan in combination in human cancer.
BACKGROUND: DNA damage caused by platinum agents is frequently followed by induction of topoisomerase I, providing a rationale for use of platinum-based compounds with topoisomerase I inhibitors. MATERIALS AND METHODS: We studied the effect of a sequential schedule of oxaliplatin on day I and topotecan on days 2-5, in human colon and ovarian cancer cells in vitro, in nude mice bearing human cancer xenografts and finally in cancer patients in a phase I trial. RESULTS: We demonstrated a supra-additive effect of this combination on inhibition of colony formation and induction of apoptosis in vitro. We then demonstrated that the two agents in combination markedly inhibit tumor growth in nude mice. We translated these results into a clinical setting, conducting a phase I study in cancer patients with oxaliplatin 85 mg/m2 on day 1 and topotecan at doses escalating from 0.5 to 1.5 mg/m2 on days 2-5. Sixty cycles of treatment were administered to 18 patients affected prevalently by ovarian and colorectal cancer. Combination with topotecan 1.5 mg/m2 caused a dose-limiting toxicity. Therefore the maximum tolerated dose of topotecan was 1.25 mg/m2, at which six patients experienced a mild hematological and gastrointestinal toxicity. We also obtained evidence of clinical activity, particularly in ovarian cancer. CONCLUSIONS: Our results provide a solid biological and clinical rationale for a phase II trial at the recommended doses of oxaliplatin 85 mg/m2 and topotecan 1.25 mg/m2, possibly in ovarian cancer patients.
Adult↗
Very young women (<35 years) with operable breast cancer: features of disease at presentation.
BACKGROUND: Breast cancer rarely occurs in young women. Our knowledge about disease presentation, prognosis and treatment effects are largely dependent upon older series. MATERIALS AND METHODS: We evaluated biological features and stage at presentation for 1427 consecutive premenopausal patients aged < or = 50 years with first diagnosis of invasive breast cancer referred to surgery at the European Institute of Oncology from April 1997 to August 2000. A total of 185 patients (13%) were aged < 35 years ('very young') and 1242 (87%) were aged 35-50 years ('less young'). The expression of estrogen receptors (ER), progesterone receptors (PgR), presence of vascular invasion (VI), grading (G), expression of Ki-67, HER2/neu overexpression, pathological stage according to TNM staging system (pTNM), pathological tumor size and number of axillary lymph node involvement were evaluated. RESULTS: Compared with less young patients, the very young patient group had a higher percentage of tumors classified as ER negative (P < 0.001), PgR negative (P = 0.001), higher expression of Ki-67 > or = 20% of cells stained; 62.2% versus 53%, (P < 0.001), vascular or lymphatic invasion (48.6% versus 37.3%, P = 0.006), and pathological grade 3 (P < 0.0001). There was no difference between the two groups for pT, pathological tumor size (pN) and number of positive lymph nodes. CONCLUSIONS: We conclude that compared with less young premenopausal patients, very young women have a greater chance of having an endocrine-unresponsive tumor, and are more likely to present with a higher grade, more extensively proliferating and vessel invading disease. Pathological tumor size, nodal status and number of positive axillary lymph-nodes have a similar distribution among the younger and the older cohorts, thus not supporting previous data indicating more advanced disease in younger patients at diagnosis of operable disease.
Adult↗
Second-line chemotherapy with a hybrid-alternating regimen of bolus 5FU modulated by methotrexate and infusional 5FU modulated by folinic acid in patients with metastatic colorectal cancer pretreated with 5FU. A phase 2 study.
BACKGROUND AND AIM: In vitro, methotrexate (MTX) is the best modulator for bolus 5-fluorouracil (5FU), whereas folinic acid (FA) is the best for continuous infusion. We evaluated the effect of 5FU modulated by both MTX (bolus administration) and FA (continuous infusion) as second-line treatment of patients with metastatic colorectal cancer. PATIENTS AND METHODS: Entry criteria were: at least one 5FU-based chemotherapy regimen as first-line treatment for metastatic disease, or progression within twelve months after 5FU-containing adjuvant therapy. Treatment schedule: MTX 200 mg/m2 i.v. days 1 and 15; 5FU 600 mg/m2 i.v. bolus, days 2 and 16; 5FU 200 mg/m2 i.v. continuous infusion for 21 days, starting on day 29; FA 20 mg/m2 i.v. bolus weekly during the three weeks of 5FU infusion. Cycles were repeated every 56 days. The primary end-point was tumour control rate, including partial responses and stabilizations. RESULTS: 34/35 patients enrolled were evaluable for response. Five (14.7%) had a partial response, 13 (38.2%) disease stabilization, and 16 (47.1%) progressed; tumour control rate was 52.9%. Median TTP was 5.8 months (95% CI 4.03-7.83); 29 patients had died. Median OAS was 15.9 months (95% CI 8.8-21.9). Toxicity was mild. CONCLUSIONS: The regimen constituted by 5FU modulated by MTX (bolus administration) and FA (continuous infusion) is active as second-line treatment of metastatic colorectal cancer.
Adenocarcinoma↗
Efficacy of anthracyclines and paclitaxel as first line chemotherapy in patients with visceral metastases of breast cancer.
BACKGROUND: Anthracyclines combined with paclitaxel are one of the most active schedules in patients with advanced breast cancer: response rates range from 40 to 80%, considering all metastatic sites (visceral and soft tissues). We performed a non-randomized phase II trial with anthracyclines/paclitaxel combination to evaluate response and toxicity only in patients with visceral metastases. METHODS: Twenty-seven patients (median age 50 years; range 30-72) with visceral metastases of breast cancer were enrolled in this study. Overall, 11 patients had lung metastases (41%), 10 liver (37%), 4 liver-lung metastases (15%) and 2 peritoneal carcinosis (7%). 7 patients had received adjuvant anthracycline-based chemotherapy (26%) and 10 patients adjuvant CMF combination chemotherapy (37%); 10 patients (37%) received hormonal therapy for advanced disease. Treatment schedules were: group A) 17 patients, Adriamicyn 50 mg/m2 on day 1 i.v. bolus and Paclitaxel 175 mg/m2 on day 2 i.v. 3 hours infusion, every 3 weeks; group B) 10 patients, epirubicin 90 mg/m2 on day 1 i.v. bolus and paclitaxel 200 mg/m2 on day 2 i.v., 3 hours infusion, every 3 weeks. The number of cycles administered was 141 with a median of 5 (range 3-9). RESULTS: All patients were evaluable for response and toxicity. The objective response rate was 59% - 16 patients - (15% complete and 44% partial remission), 95% C.I. 40.7-77%; 10/17 in group A and 7/10 in group B. Stable disease 30% (8 patients) and progressive disease 11% (3 patients). The median duration of response was 5 months (range 1-16); median time to progression 13 months (range 3-18) and median survival 17 months (range 4-24). The main toxicity was neutropenia, occurred in 16 patients (59%; grade IV in 7 patients, of whom 2 febrile neutropenia, and grade III in 9 patients); grade III gastrointestinal toxicity in 2 patients; grade III neurological toxicity in 1 patient; grade III stomatitis in 2 patients. No congestive hearth failure or treatment death related was observed. CONCLUSIONS: These schedules of anthracyclines and paclitaxel confirmed their efficacy in metastatic breast cancer even in patients with visceral disease. Neutropenia was the main toxicity; grade IV neutropenia was more frequently observed in epirubicin/paclitaxel arm.
Adult↗
Potential role and chronology of abnormal expression of the Deleted in Colon Cancer (DCC) and the p53 proteins in the development of gastric cancer.
BACKGROUND: Loss of activity of tumor suppressor genes is considered a fundamental step in a genetic model of carcinogenesis. Altered expression of the p53 and the Deleted in Colon Cancer (DCC) proteins has been described in gastric cancer and this event may have a role in the development of the disease. According to this hypothesis, we investigated the p53 and the DCC proteins expression in different stages of gastric carcinomas. METHODS: An immunohistochemical analysis for detection of p53 and DCC proteins expression was performed in tumor tissue samples of patients with UICC stage I and II gastric cancer. For the purpose of the analysis, the staining results were related to the pathologic data and compared between stage categories. RESULTS: Ninety-four cases of gastric cancer were analyzed. Disease stage categories were pT1N0 in 23 cases, pT2N0 in 20 cases, pT3N0 in 20 cases and pT1-3 with nodal involvement in 31 cases. Stage pT1-2N0 tumors maintained a positive DCC expression while it was abolished in pT3N0 tumors (p <.001). A significant higher proportion of patients with N2 nodal involvement showed DCC negative tumors. In muscular-invading tumors (pT2-3N0) the majority of cases showed p53 overexpression, whereas a significantly higher proportion of cases confined into the mucosa (pT1N0) showed p53 negative tumors. Also, a higher frequency of p53 overexpression was detected in cases with N1 and N2 metastatic lymph nodal involvement. CONCLUSIONS: Altered expression of both DCC and p53 proteins is detectable in gastric carcinomas. It seems that loss of wild-type p53 gene function and consequent p53 overexpression may be involved in early stages of tumor progression while DCC abnormalities are a late event.
Aged↗
Vascular endothelial growth factor expression, S-phase fraction and thymidylate synthase quantitation in node-positive colon cancer: relationships with tumor recurrence and resistance to adjuvant chemotherapy.
BACKGROUND: The behaviour of colorectal carcinomas may depend on molecular properties of tumors. In node-positive colon cancer, we assessed the S-phase fraction (SPF) index, the vascular endothelial growth factor (VEGF) expression and the TS levels. The combined analysis of SPF/VEGF was studied for predictivity of recurrent disease, the TS quantitation was related to the efficacy of fluorouracil-based adjuvant chemotherapy. PATIENTS AND METHODS: Consecutive patients with surgically-resected, node-positive colon cancer were studied. Flow cytometry for the SPF and immunohistochemistries for the TS and the VEGF expression were carried out on the primary tumor. Recurrences had to be proven by biopsy or surgery, and they were categorized as early, if occurred within 12 months after surgery, or late if occured 13 months or more. RESULTS: Of 150 evaluable patients, 100 had received fluorouracil-based adjuvant chemotherapy and 50 control patients were untreated. The combined analysis of the VEGF and the SPF showed a strong association between the two markers; 48 patients (32%) had high SPF/VEGF positive tumors and 69 patients (46%) had low SPF/VEGF negative tumors (P < 0.0001). The majority of disease-free patients (73.4%) showed VEGF negative/low SPF tumors (P < 0.0001). Early recurrences occurred more frequently in patients with VEGF positive/high SPF tumors (P < 0.001). In the 100 patients treated with adjuvant chemotherapy, 86% of relapsed patients had TS overexpressing tumors and 69% of disease-free patients had TS negative tumors (P < 0.001). Also, early recurrences occurred more frequently in TS overexpressing tumors (P < 0.0001). CONCLUSIONS: Evidence is supported that node-positive colon cancer constitutes a heterogenous disease. Patients with VEGF positive/high SPF tumors showed an unfavourable outcome compared to patients with VEGF negative/low SPF tumors. The efficacy of fluorouracil-based adjuvant chemotherapy may depend on the TS status.
Adult↗
The utility of laboratory screening in medically III patients with psychiatric symptoms.
The presence of psychiatric illness in general hospital medical inpatients can complicate a patient's clinical course. Currently, there is no standard laboratory work-up recommended for this patient population. To begin to assess the utility of a routine panel of tests, the results of serum vitamin B12 (cobalamin) levels, folate levels, thyroid stimulating hormone levels, and syphilis serology of 349 patients were reviewed. These patients had been admitted to the hospital for nonpsychiatric conditions but either had preexisting psychiatric disturbances or developed a mood spectrum disorder or cognitive spectrum disorder during their hospitalization. The incidence of vitamin B12 and folate deficiencies in these patients was found to be higher than has been reported for the general population. Thus, routine screening for these vitamin deficiencies may be indicated because of their prevalence in this patient population.
Adolescent↗
Effects of selenium and zinc supplementation on nutritional status in patients with cancer of digestive tract.
OBJECTIVE: To evaluate the effect of oral administration of selenium and zinc tablets in patients with cancer of the digestive tract during chemotherapy. DESIGN: A case-control, randomized study. SETTING: Medical Oncology, II University of Naples, Naples, Italy. SUBJECTS: A total of 60 patients (median age 55 y, range 46-61 y) with diagnosis of gut cancer were randomized in 1999. Patients were treated for 60 days with chemotherapy. INTERVENTIONS: Trace elements were measured by atomic absorption spectroscopy. The nutritional status of the patients was assessed by biochemical and bio-impedance analysis (BIA) parameters in basal condition and after 60 days of treatment. Oral administration of selenium and zinc in oral tablet form for 50 days was Se 200 microg/day (50 microg/tablet) and Zn 21 mg/day (7 mg/tablet). RESULTS: Both in the basal condition and at 60 days all patients were malnourished. Selenium and zinc concentrations were significantly lower (P < 0.01) whereas copper concentration was significantly higher (P < 0.01) in cancer patients than in control subjects. However, 21/30 (70%) of those treated with Se and Zn did not showed a further worsening of nutritional status and experienced a significant decrease of asthenia with an increase of appetite. On the other hand, 24/30 (80%) untreated patients had a significant decline of all parameters studied after 60 days (prealbumin, cholesterol, transferrin, P < 0.05 vs 0 time; total proteins, albumin/globulin ratio, P < 0.01 vs 0 time; fat-free mass, fat mass, Na+/K+ ratio, body mass index P < 0.05 vs 0 time; fat free mass/fat mass, total body water, extra cellular/intra cellular water, basal metabolic rate: P < 0.01 vs 0 time). CONCLUSIONS: Data indicate that Se and Zn supplementation may improve the clinical course of general conditions in patients with gut cancer. These effects of Se and Zn require confirmation in an independent trial of appropriate design before new public health recommendations regarding Se and Zn supplementation can be made.
Case-Control Studies↗
A phase II study of sequential chemotherapy with docetaxel after the weekly PELF regimen in advanced gastric cancer. A report from the Italian group for the study of digestive tract cancer.
In advanced gastric cancer, we investigated feasibility and activity of sequential chemotherapy with docetaxel after an intensive weekly regimen consisting of cisplatin, epidoxorubicin, fluorouracil, leucovorin (PELF) plus filgrastim. Chemotherapy-naive patients with relapsed or metastatic gastric cancer received 8 weekly administrations of chemotherapy with cisplatin 40 mg/m(2), fluorouracil 500 mg/m(2), epidoxorubicin 35 mg/m(2), 6S-stereoisomer of leucovorin 250 mg/m(2) and glutathione 1.5 g/m(2). On the other days filgrastim 5 microg kg(-1) was administered by subcutaneous injection. Subsequently, patients with partial response or stable disease received 3 cycles of docetaxel 100 mg/m(2) every 3 weeks. 40 patients have been enrolled and they are evaluable for response and toxicity. After the PELF regimen, 3 patients achieved complete response, 13 patients showed partial response, 21 patients had stable disease and 3 patients progressed (40% response rate; 95% CI 25% to 55%). After docetaxel, 9 out 34 patients improved the outcome (26.5%); 7 patients with stable disease achieved partial response and 2 patients with partial response achieved complete response. The overall response rate in the 40 patients was 57.5% (95% CI, 42.5% to 72.5%). The PELF regimen did not cause any grade IV toxicity, the most frequent grade III acute side-effects were thrombocytopenia and vomiting which occurred in the 10% of 320 PELF cycles. Docetaxel caused grade III-IV neutropenia and thrombocytopenia in the 10% and the 19% of cycles respectively. Fatigue was a frequent side-effect during both PELF and docetaxel chemotherapy. The sequential application of docetaxel after PELF chemotherapy gained major objective responses with manageable toxicity. This strategy is worth of further investigation in the setting of palliative or neoadjuvant chemotherapy.
Adult↗
Inhibition of vascular endothelial growth factor by octreotide in colorectal cancer patients.
Vascular endothelial growth factor (VEGF) seems to be essential for angiogenesis and for the growth of colorectal cancer; thus its inhibition can arrest tumor growth and decrease metastatic potential. Octreotide has been shown to inhibit growth of colorectal tumors in vitro and in vivo. Part of the antiproliferative activity of octreotide could be related to its antiangiogenic properties. Effects of octreotide on VEGF expression were evaluated in 35 patients with operable colorectal cancer receiving octreotide for 2 weeks before surgery. Tissue VEGF expression and serum VEGF concentrations were determined before and after treatment with octreotide. There was a statistically significant reduction in the tissue VEGF expression both considering the percentage of VEGF positive cells (P = 0.006) and the intensity of VEGF staining (P = 0.003). A similar significant reduction was observed in serum values of VEGF (P = 0.03). The present study indicates that octreotide inhibits expression of VEGF in colorectal cancer patients, and, furthermore, that serum VEGF expression correlates with tissue VEGF, representing a safe method to monitor the activity of antiangiogenic agents.
Aged↗