Background & objectives:Imatinib is the standard first-line treatment for chronic myeloid leukaemia (CML) patients. About 20 to 30 per cent patients develop resistance to imatinib and fail imatinib treatment. One of the mechanisms proposed is varying expression levels of the drug transporters. This study was aimed to determine the expression levels of imatinib transporter genes (OCT1, ABCB1, ABCG2) in CML patients and to correlate these levels with molecular response.Methods:Sixty three CML chronic phase patients who were on 400 mg/day imatinib for more than two years were considered for gene expression analysis study for OCT1, ABCB1 and ABCG2 genes. These were divided into responders and non-responders. The relative transcript expression levels of the three genes were compared between these two categories. The association between the expression values of these three genes was also determined.Results:No significant difference in the expression levels of OCT1, ABCB1 and ABCG2 was found between the two categories. The median transcript expression levels of OCT1, ABCB1 and ABCG2 genes in responders were 26.54, 10.78 and 0.64 versus 33.48, 7.09 and 0.53 in non-responders, respectively. A positive association was observed between the expression of the ABCB1 and ABCG2 transporter genes (r=0.407, P<0.05) while no association was observed between the expression of either of the ABC transporter genes with the OCT1 gene.Interpretation & conclusions:Our findings demonstrated that the mRNA expression levels of imatinib transporter genes were not correlated with molecular response in CML patients. Further studies need to be done on a large sample of CML patients to confirm these findings.
Background: There are very few options for the treatment of patients of SCCHN who relapse after surgery and/or radiotherapy and/or chemotherapy other than best supportive care (BSC). Over expression of the EGFR has been demonstrated in more than 80% of patients with SCCHN. In the present study, we compared the response rates, overall survival, toxicity profile and quality of life in patients of recurrent SCCHN receiving oral methotrexate versus a combination of EGFR inhibitor (Gefitinib) + COX II inhibitor (Etoricoxib). Patients and Methods: Twenty five patients of Advanced and Recurrent HNSCC were included in each group. Patients were randomly assigned to receive Gefitinib (250 mg twice a day before meals) plus Etoricoxib (120 mg/day) [Group A] or Oral Methotrexate (15 mg/week) [Group B]. All patients received BSC. Patients were follow-up 4 weekly with routine blood investigations and quality of life questionnaires - QLQ C-30 and QLQ H & N-35. CT scan of Head and Neck was done every 8 weeks. EGFR mutation studies were not performed. Results : Partial Response (PR) was seen in 6.25% of patients in group-A; and 0% from group-B. Stable Disease (SD) observed in 25% of patients from group-A and 10% patients from group-B. At the end of study, mean overall survival (OS) in group-A was 107.15 days; whereas mean overall survival in group-B was 73.95 days. The difference in survival was statistically significant (P<0.05). Comparing the QOL between two groups by EORTC QLQ C-30 and EORTC H & N-35 at 4 and 8 weeks, patients of group-A had better quality of life. No dose-limiting toxicities were seen in group-A or B. Most common toxicity observed in group A were skin rash and diarrhoea while on group B it was mucositits. Conclusions: In this small pilot study, in patients with advanced and recurrent SCCHN, dual targeted treatment (EGFR and COX II) with combination of Gefitinib plus Etoricoxib improved response rates, quality of life and overall survival as compared to oral methotrexate. The combination was well tolerated with minor side-effects and should be considered in this poor prognostic subset of patients. Larger, multi-centric studies are needed to confirm these results. Citation Format: Hemant Malhotra, Archit Joshi, Sandeep Jasuja, Ajay Yadav. Gefitinib [epidermal growth factor receptor (EGFR) inhibitor] plus etoricoxib (COX-2 inhibitor) versus oral methotrexate in advanced, recurrent head and neck squamous cell carcinoma (HNSCC): results of a randomized pilot study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2582. doi:10.1158/1538-7445.AM2015-2582
Background/Aim: Pharmacovigilance in oncology is imperative as antineoplastic drugs are two-edged swords whose irrational use can pose a major health problem and a needless financial burden on the patient. The aim of this study was to study the comprehensive safety profile of anti-neoplastic drugs used for treating oral cancers. Methods: This hospital-based prospective observational study was conducted at two premiers (a government and a private) tertiary care centres in North-Western India among newly diagnosed cases of oral cancers of both sexes between the ages of 20-70 years and requiring chemotherapy treatment. The prescribing pattern of chemotherapy drugs, associated adverse effects and potential risk factors for the development of adverse effects was studied. An adverse drug reaction (ADR) causality was assessed by the WHO-UMC algorithm and preventability by Schumock and Thornton's criteria. Univariate and multivariate logistic regression analyses were used to identify the predictors related to chemotherapy-induced adverse effects. Results: The data concerned 188 patients, of which 64.3 % developed chemotherapy-related adverse effects. Among the prescribed anti-neoplastic drugs, a combination of 5-Fluorouracil, Cisplatin and Paclitaxel regimen was associated with the majority (91.42 %) of the adverse effects. Alopecia was the most common adverse effect noted in 26.44 % of patients, followed by nausea and anaemia in 15.7 % and 9.9 % of patients, respectively. Independent predictors of chemotherapy-related adverse effects were site (Adjusted odds ratio [AOR] = 1.95; 95 % CI 1.04 - 3.62, p = 0.03), chemotherapy and radiotherapy treatment (AOR = 5.00; 95 % CI 2.62 - 9.53, p < 0.001), combination regimen of 5-Fluorouracil, Cisplatin and Paclitaxel (AOR = 8.68; 95 % CI 2.55 - 29.48, p = 0.001), associated comorbidities (AOR = 16.68; 95 % CI 2.45 - 28.34, p < 0.001). Causality assessment revealed most adverse effects (82.64 %) to be possible. Conclusion: The adverse effect varies with the type of regimen which is prescribed for the patient. Site of cancer, concomitant radiotherapy treatment and associated comorbidities were the identifiable risk factors for developing adverse effects. Onco-pharmacovigilance studies in the future will help to provide tailored treatment to patients and improve their quality of life.
Background: In recent years there has been a re-awakening of interest in the identification of Medicinal plants and their derivatives for the treatment of human diseases including cancer. The present work aims to investigate the in-vitro activity of two plants used in traditional Indian medicine - Zingiber Officinale Rose(Rhizome) and Nerium Oleander L(Leaves) against a human leukemic cell line. Method: The plants were extracted with methanol and ethanol using soxalate apparatus. In-vitro anti-cancer activity was screened against leukemic cell line K562 using the SRB and MTT assay. Apoptosis and DNA fragmentation were characterized by PI staining flow cytometry and Gel electrophoresis, respectively. Results: Notable cancer cell growth inhibition was observed for extracts from Zingiber Officinale Rose and Nerium Oleander L with IC50 values ranging between 10 -28 μg/ml. Furthermore, treatment of cells with both the extracts was shown to produce cell cycle arrest and DNA damage indicating that the observed cytotoxicity was mediated via apoptosis. Conclusion: Extracts of Ginger and Oleander has anti-cancer activity against the K572 cell line in an in-vitro system. Based upon this initial screening work reported here, further studies aimed at the identification of active components of these extracts are planned. The activity of these agents against cell lines developed from actual patient samples are also planned. Citation Format: Hemant Malhotra, Bharti Malhotra, Shipra Bhargava, Om Singh Rathode, Pratibha Sharma, Ashwin Mathur, Sandeep Jasuja, Shubha V. Chiplunkar. Anti-leukemic activities of alcoholic extracts of two traditional Indian medicinal plants. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2248. doi:10.1158/1538-7445.AM2013-2248
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