Cisplatin plus oral etoposide (EoP) combination is more effective than paclitaxel in patients with advanced breast cancer pretreated with anthracyclines: a randomised phase III trial of Turkish Oncology Group

Our objective was to determine whether oral etoposide and cisplatin combination (EoP) is superior to paclitaxel in the treatment of advanced breast cancer (ABC) patients pretreated with anthracyclines. From December 1997 to August 2003, 201 patients were randomised, 100 to EoP and 101 to paclitaxel arms. Four patients in each arm were ineligible. The doses of etoposide and cisplatin were 50 mg p.o. twice a day for 7 days and 70 mg m−2 intravenously (i.v.) on day 1, respectively, and it was 175 mg m−2 on day 1 for paclitaxel. Both treatments were repeated every 3 weeks. A median of four cycles of study treatment was given in both arms. The response rate obtained in the EoP arm was significantly higher (36.3 vs 22.2%; P=0.038). Median response duration was longer for the EoP arm (7 vs 4 months) (P=0.132). Also, time to progression was significantly in favour of the EoP arm (5.5 vs 3.9 months; P=0.003). Median overall survival was again significantly longer in the EoP arm (14 vs 9.5 months; P=0.039). Toxicity profile of both groups was similar. Two patients in each arm were lost due to febrile neutropenia. The observed activity and acceptable toxicity of EoP endorses the employment of this combination in the treatment of ABC following anthracyclines

Helicobacter pylori regulates iNOS promoter by histone modifications in human gastric epithelial cells. [R. Pero* corresponding author]

Inducible nitric oxide synthase (iNOS) expression is altered in gastrointestinal diseases. Helicobacter pylori (Hp) infection may have a critical role in iNOS disregulation. We undertook this study to investigate possible chromatin changes occurring early during iNOS gene activation as a direct consequence of Hp???gastric cells interaction. We show that Hp infection is followed by different expression and chromatin modifications in gastric cells including (1) activation of iNOS gene expression, (2) chromatin changes at iNOS promoter including decreased H3K9 methylation and increased H3 acetylation and H3K4 methylation levels, (3) selective release of methyl-CpG-binding protein 2 from the iNOS promoter. Moreover, we show that Hp-induced activation of iNOS is delayed, but not eliminated, by the treatment with LSD1 inhibitors. Our data suggest a role for specific chromatin-based mechanisms in the control of human iNOS gene expression upon Hp exposure

The use of recombinant human granulocyte colony-stimulating factor in combination with single or fractionated doses of ifosfamide and doxorubicin in patients with advanced soft tissue sarcoma

PubMedID: 8808721Sixty patients with stage III-B and IV soft tissue sarcomas were randomized to receive either ifosfamide 5 g/m2xdx1 and doxorubicin 60 mg/m2xdxl given every 3 weeks (arm A) or ifosfamide 1.8 g/m2xdx5 and doxorubicin 60 mg/m2xdx1 given every 4 weeks (arm B). Recombinant human granulocyte colony-stimulating factor (r-met Hu G-CSF: 250 µg/m2xd) was applied with a prophylactic intent to patients in arm A only. The response rate was higher in arm A patients (56% versus 33%, p = 0.03). In stage III patients, the complete response rate was significantly higher (53% versus, 13.3%, p = 0.01) and the duration of response was significantly longer in arm A (20 ± 8.2 months versus, 13.4 ± 7 months, p = 0.05). Chemotherapy related myelotoxicity and mucositis were also less frequent in this arm as a result of propylactic r-met Hu G-CSF administration (p = 0.04, p = 0.003). It was concluded that single dose ifosfamide and doxorubicin combinations deserve further investigation under the cover of hematopoietic growth factors, particularly in patients with stage III soft tissue sarcomas

Palmar-plantar erythrodysesthesia due to docetaxel-capecitabine therapy is treated with vitamin E without dose reduction

PubMedID: 16188440Palmar-plantar erythrodysesthesia (PPE) is a distinctive and relatively frequent toxic reaction related to some chemotherapeutic agents. Doxorubicin, cytarabine, docetaxel, fluorouracil, and capecitabine are the most frequently implicated agents. Recently, taxanes, especially docetaxel, have been widely used in combination with capecitabine in patients with metastatic breast cancer (MBC). A high percentage of PPE has been seen in patients undergoing this combination therapy. PPE seems to be dose dependent and both peak drug concentration and total cumulative dose determine its occurrence. Withdrawal or dose reduction of the implicated drug usually gives rise to amelioration of the symptoms. Supportive treatments such as topical wound care, elevation, and cold compresses may help to relieve the pain. Use of systemic corticosteroids, pyridoxine (vitamin B6), blood flow reduction, and, recently, topical 99% dimethyl-sulfoxide have been used with variable outcomes. Vitamin E treatment has not been published before, especially without dose reduction of docetaxel-capecitabine therapy. Here we present five MBC patients treated with docetaxel-capecitabine combination therapy in whom PPE was observed during the clinical follow-up period. In all patients grade 2-3 PPE was observed. Vitamin E therapy was started at 300 mg/day p.o. without dose reduction of therapy and after 1 week of treatment PPE began to disappear. We suggest that it could be of interest to consider vitamin E as a preventive drug when drugs with a strong association with PPE are going to be administered. © 2005 Elsevier Ltd. All rights reserved

Supportive treatment in weight-losing cancer patients due to the additive adverse effects of radiation treatment and/or chemotherapy

PubMedID: 11277319The reversal of anorexia and weight loss especially in patients with advanced cancer suffering from radiation treatment (RT) -related complications and debilitated furtherly during RT would be a welcome relief. The purpose of this study is to evaluate the feasibility of supportive treatment with megestrol acetate (MA) in our weight-losing cancer patients increasingly experiencing anorexia, smell, taste, and weight loss due to the additive adverse effects of RT ± chemotherapy and how MA changes the additive role of the severity of RT reactions on such patients. From June 1997 to October 1998, 100 eligible patients were enrolled on a randomized, placebo-controlled clinical trial. Of the 100 patients, 46 received MA during RT and 4 after the end of the RT, and 50 received placebo for 3 months. Subjective parameters were assessed by a brief questionnaire form based on scoring from 1 to 5, according to the degree of the loss or change for each parameter of malnutrition, appetite, taste and smell developed by us. At the end of the study a statistically significant weight gain was achieved in the patient group receiving MA compared to the placebo group (+ 3 to +5 kg versus -3.7 to -5.9 kg, p=0.000). Significant improvements were seen in performance status (p=0.000), appetite (p=0.000), malnutrition (p=0.000), loss of taste (p=0.000) and smell qualities (p=0.02) in the MA group compared to the placebo group. In the MA group there was no statistically significant difference related to the weight changes according to the grade of either the acute, or late RT effects (p=0.65 and 0.07, respectively). Whereas, in the placebo group a statistically significant additive effect of the acute and late RT effects was detected on weight loss (p=0.008 and 0.007, respectively). We observed no side-effects of MA in a 3-month time follow-up. The use of MA 480 mg/day during RT was effective in reversing anorexia and weight loss in spite of the acute RT effects, and helped most patients to well tolerate specific tumor therapy. Further evaluation of its mechanisms of action on RT-related adverse effects, tumor response relationships, and effect on patient survival are researched

Palmar-plantar erythrodysesthesia due to capecitabin is treated with vitamin E without dose reduction

ESMO Scientific and Educational Conference (ESEC) -- JUN 02-05, 2005 -- Budapest, HUNGARYWOS: 000229977400231…European Soc Med Onco

Human papillomavirus in pterygium.

PubMedID: 8082148Between August 1991 and 1992 consecutive pterygium cases and eight normal conjunctival tissues were examined for the presence of polyclonal Human Papilloma Virus (HPV) antigen by the avidin-biotin-complex technique and 16 of the pterygium cases and 25 pc of the control conjunctivas revealed HPV positivity. In six of the HPV positive pterygium tissues, there were also an epithelial proliferation. In conclusion, HPV infection was not endemic, but sporadic in Cukurova region, and it may be contributed to development of pterygium. In addition, because it is seen together with six cases of epithelial hyperplasia, it seems to play an important role in the development of neoplasia and such patients need to be followed up for possible malignant transformation

A randomised trial of two cisplatin-containing chemotherapy regimens in patients with Stage III-B and IV non-small cell lung cancer

PubMedID: 7655833Seventy-four newly diagnosed patients with histologically proven Stage III-B and IV non-small cell lung cancer were randomized to receive either cisplatin: 20 mg/m2 × day × 5, ifosfamide: 1.8 g/m2 × day × 5, mesna: 1.2 g/m2 × day × 5, etoposide: 100 mg/m2 × day × 5 (ICE) or cisplatin: 20 g/m2 × day × 5 and etoposide: 100 mg/m2 × day × 5. Response rates were 59% in the ICE and 40% in the CE arm with a significant advantage in response duration and overall survival in the ICE receiving patients (P = 0.03, P = 0.0008). As we used granulocyte colony stimulating factor (G-CSF) very frequently, myelotoxicity remained substantial but acceptable. © 1995

A TRIAL OF 2 FLUOROURACIL CONTAINING ADJUVANT CHEMOTHERAPY REGIMENS IN THE TREATMENT OF THE PATIENTS WITH COLORECTAL CANCER

XVI International Cancer Congress -- OCT 30-NOV 05, 1994 -- NEW DELHI, INDIAWOS: A1994BD09K00371