In Vitro Biological Activities of Drepanoalpha® Ethanolic Extract, A Justicia Secunda and Moringa Oleifera-Based Phytomedicine Proposed for The Symptomatic Treatment of Sickle Cell Disease

Sickle cell disease (SCD) is an autosomal recessive blood disorder characterized by red blood cells that assume an abnormal, rigid sickle shape under low-oxygen conditions. These sickle-shaped erythrocytes tend to lyse, aggregate, and obstruct small blood vessels, leading to major complications. The present study aims to investigate properties that may underlie the activity of Drepanoalphaâ, an antisickling herbal formulation developed in the Democratic Republic of Congo (DRC) for the prevention and symptomatic treatment of sickle cell disease crises. The Drepanoalpha® Ethanolic Extract (DEE) is a dry extract (drug-extract ratio, DER, 100/11) prepared from ethanol (96 %, v/v) percolation of a 1:1 mixture of 2 food plants, Justicia secunda Vahl and Moringa oleifera Lam. Sickling was classically measured by light microscopy on diluted washed erythrocytes obtained from homozygote patients; erythrocytes were treated with 2 % Na2S2O5 in the presence of DEE (suspension in 9 ‰ NaCl), 9 ‰ NaCl (negative control) or disodium cromoglycate (DSCG, positive control). For all tested conditions, the sickle hemoglobin polymerization, the Fe2+/Fe3+ ratio, and the median corpuscular fragility were measured by spectrophotometry. The DEE reversed sickling by 89.1 %, comparable to DSCG (87.7 %; 60.3 µg/mL), inhibiting sickle cell hemoglobin polymerization of 77.8 % and 74.4 %, respectively. The Fe2+/Fe3+ ratio was improved by 18.0 % for DEE and 15.9 % for DSCG. The median corpuscular fragility values were 0.602, 0.714, and 0.732 for NaCl 9 ‰, DSCG, and DEE, respectively. The measured in vitro parameters validate an effective antisickling effect of DEE and confirm the value of this improved traditional herbal formulation for the management of SCD

Sentinel Node Identification Rate and Nodal Involvement in the EORTC 10981-22023 AMAROS Trial

Background The randomized EORTC 10981-22023 AMAROS trial investigates whether breast cancer patients with a tumor-positive sentinel node biopsy (SNB) are best treated with an axillary lymph node dissection (ALND) or axillary radiotherapy (ART). The aim of the current substudy was to evaluate the identification rate and the nodal involvement. Methods The first 2,000 patients participating in the AMAROS trial were evaluated. Associations between the identification rate and technical, patient-, and tumor-related factors were evaluated. The outcome of the SNB procedure and potential further nodal involvement was assessed. Results In 65 patients, the sentinel node could not be identified. As a result, the sentinel node identification rate was 97% (1,888 of 1,953). Variables affecting the success rate were age, pathological tumor size, histology, year of accrual, and method of detection. The SNB results of 65% of the patients (n = 1,220) were negative and the patients underwent no further axillary treatment. The SNB results were positive in 34% of the patients (n = 647), including macrometastases (n = 409, 63%), micrometastases (n = 161, 25%), and isolated tumor cells (n = 77, 12%). Further nodal involvement in patients with macrometastases, micrometastases, and isolated tumor cells undergoing an ALND was 41, 18, and 18%, respectively. Conclusions With a 97% detection rate in this prospective international multicenter study, the SNB procedure is highly effective, especially when the combined method is used. Further nodal involvement in patients with micrometastases and isolated tumor cells in the sentinel node was similar—both were 18%

An EORTC phase II study of sequential methotrexate-fluorouracil in locally advanced or metastatic gastric cancer

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An EORTC Gastrointestinal (GI) Group randomized evaluation of the toxicity of sequential high dose methotrexate and 5-fluorouracil combined with adriamycin (FAMTX) vs 5-fluorouracil, adriamycin and mitomycin (FAM) in advanced gastric cancer

Until now advanced gastric cancer has been generally treated with the FAM chemotherapy protocol. Due to the relatively low response rates with this protocol we decided to start a randomized prospective phase II trial comparing the FAM with the FAMTX protocol. The primary aim of our trial was to compare the toxicity in both protocols. The FAMTX protocol has been demonstrated to be fully comparable with the toxicity of the FAM protocol. The trial has been extended to a phase III study. With respect to response rates and survival times it is too early for evaluation. © 1989, Humana Press Inc. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Final results of a randomized trial on the treatment of rectal cancer with preoperative radiotherapy alone or in combination with 5‐fluorouracil, followed by radical surgery trial of the european organization on research and treatment of cancer gastrointestinal tract cancer cooperative group

To improve surgical results of potentially operable rectal cancer, the European Organization on Research and Treatment of Cancer conducted a two‐arm randomized clinical trial to compare the efficiency of preoperative administration of radiotherapy, with or without 5‐fluorouracil before radical surgery. Two hundred forty‐seven eligible patients were admitted from November 1972 through April 1976. The overall survival observed in the group treated with preoperative radiotherapy appears to be better than in the group of patients where preoperative combined modality was administered. Five‐year survival is 59% versus 46% with a marginal statistical significance of P = 0.06. Although the combined modality arm had a higher incidence of side effects and postoperative deaths, it had a greater effect than the radiotherapyalone arm in controlling the disease process, mainly distant metastases to the liver with a result bordering on statistical significance (P = 0.07). The incidence of nonmalignant and intercurrent deaths were higher in the combined modality group, whereas deaths due to malignancy were higher in the radiotherapyalone group. Observing more stringent selection in disease and patients' criteria, side effects and intercurrent deaths can be effectively reduced with further improvement in adjuvant therapy results. Copyright © 1984 American Cancer SocietySCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe

Treatment of patients with irresectable liver metastases from colorectal cancer by chemo‐occlusion with degradable starch microspheres

Chemo‐occlusion of the liver increases the tumour concentration of drugs. Thirty‐nine patients with colorectal liver metastases received a monthly bolus administration of mitomycin C (10 mg/m2 on day 1) plus a continuous infusion of 5‐fluorouracil (500 mg/m2 daily from days 1 to 5). Drugs were given via both portal (one‐third of the dose) and arterial (two‐thirds) routes to control large and small metastases. Arterially administered mitomycin C was mixed with individualized doses of degradable starch microspheres. In 16 patients treatment was not started or was interrupted early because of arterial or portal catheter problems. In 23 patients who received two or more cycles of treatment the mean (s.d.) microsphere dose was 835(399) mg. Toxicity was mild, consisting mainly of pain. Five complete and five partial responses were seen, and six patients had stable disease. The median time to progression and length of survival were 6 and 16 months respectively. The relatively high rates of complete and overall response in hypovascular tumours (six of 12 lesions) may support the rationale of chemo‐occlusion. Copyright © 1994 British Journal of Surgery Society Ltd.SCOPUS: ar.jFLWNAinfo:eu-repo/semantics/publishe

Phase II study of epirubicin in advanced adenocarcinoma of the pancreas

The EORTC Gastrointestinal Group has conducted a phase II trial in 41 patients with locally advanced or metastatic adenocarcinoma of the pancreas with epirubicin 90 mg/m2 intravenously every 4 weeks, with dose escalation if possible. Seven patients were not evaluable for response. In 34 evaluable patients there were two complete and six partial responses (response rate 24%). Nine patients had stable disease for at least 2 months, including one patient with a minor response. Median time to progression for responders was 7 months, for all patients 3 months. Median survival for responders was 9 months, for all patients 5 months. It is concluded that epirubicin is an active drug in pancreatic cancer. © 1985.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Adjuvant therapy of poor prognosis colon cancer with levamisole: Results of an EORTC double‐blind randomized clinical trial

From 1978 to 1985, 297 patients were entered in a double‐blind randomized trial comparing levamisole to placebo as adjuvant therapy of Dukes' C carcinoma of the colon. Therapy consisted of from two to five tablets of 50 mg levamisole (or placebo) twice a week, depending on bodyweight for 1 year. Levamisole was generally well tolerated, with only four reversible cases of agranulocytosis reported among 129 patients. The trial failed to show a benefit of levamisole on disease‐free survival (P = 0·53) or on survival (P = 0·35). There was no difference between the two treatment groups in terms of number of disease relapses, sites of relapse, or time to relapse. The proportion of patients still alive at 5 years was 51 per cent (standard error, 5·5 per cent) in the levamisole group versus 39 per cent (standard error, 5·4 per cent) in the placebo group. Copyright © 1989 British Journal of Surgery Society Ltd.SCOPUS: ar.jFLWNAinfo:eu-repo/semantics/publishe

An EORTC gastrointestinal group phase II evaluation of epirubicin combined with ifosfamide in advanced adenocarcinoma of the pancreas

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The value of preoperative radiotherapy in esophageal cancer: Results of a study of the E.O.R.T.C.

Attempts to combine radiation therapy and surgery in patients with operable carcinoma of the esophagus began 30 years ago. The first reported surgical series showed a low rate of resectability and a high postoperative mortality. Results of radiation therapy alone were also disappointing in the long run, especially in patients who appeared to be excellent operative risks with small localized tumors. The rationale for a combined approach was that x-ray therapy could bring about a reduction of tumor activity and bulk, an improvement in nutritional state through the restoration of the ability to swallow, a reduction of transplantability of the tumor, and a curative effect on periesophageal regional disease which is not treated well by surgery. On the other hand, surgery often allowed an extended resection, clearing residual foci or distant esophageal wall extension. The limit of a combined approach is the toxicity of the preoperative radiation which must be mild enough to allow surgery to proceed without excessive delay or increased mortality. Numerous radiotherapy schedules were tried using different fields, doses, and fractionations, most of them in nonrandomized studies. Two prospective randomized trials have been recently reported. The final results of a third prospective trial, run by the E.O.R.T.C. will be presented. © 1987 Société Internationale de Chirurgie.SCOPUS: ar.jinfo:eu-repo/semantics/publishe