Del Priore G.,Indiana University |
Gudipudi D.K.,Indo American Cancer Institute and Research Center |
Restivo A.M.,Umass Memorial Medical Center Memorial Campus Worcester |
Arslan A.A.,New York University
Gynecologic Oncology | Year: 2010
Objective: Standard surgical treatment for CIN may impair fertility generating a need for alternative treatment options. We tested the efficacy and toxicity of oral DIM in the treatment of CIN 2 or 3 lesions. Methods: Patients with biopsy-proven cervical intraepithelial neoplasia (CIN) 2 or 3 scheduled for loop electrosurgical excision procedure (LEEP) were randomized 2:1 to receive diindolylmethane (DIM) (BioResponse-DIM®, BioResponse, Boulder, CO) orally at approximately 2 mg/kg/day for 12 weeks or placebo (defatted rice bran, BioResponse). Subjects were evaluated every 3-4 months for 1 year. Analysis of data up to 1 year was assessed including Pap smear, HPV, colposcopy, biopsy and physical examination were performed at follow-up. Central pathology review confirmed all histology diagnoses. Results: To date, 64 subjects (mean age 28 years, range 18-61) have been enrolled (45 in the DIM arm, 19 in the placebo arm), with 60 available for analysis. Average follow-up was 6 months. At enrollment, 58% were diagnosed with CIN 2 and 42% with CIN 3, 57% of subjects were Caucasian, 15% African American, 12% Hispanic and 17% Asian. During treatment 2 subjects (3%) complained of nausea (grade 2) at the 3- to 4-month visit. No systemic toxicities were observed (normal CBC, LFTs, comprehensive metabolic). Forty-six subjects had biopsies at first follow-up (77%). Twenty-one subjects (47%) in the DIM group had improved CIN with a decrease by 1-2 grades or a normal result. Median time to improvement was 5 months. Improved Pap smear was seen in 49% (22/45) with either a less severe abnormality or normal result. Colposcopy improved in twenty-five subjects in the DIM group (56%). Of these 25 subjects, 21 (84%) had improved colposcopic impression, 13 (52%) had a decrease in involved quadrants and 18 (72%) had a decrease in lesion number. Complete colposcopic response was observed in 4 subjects (9%). Stratifying by level of dysplasia, age, race, HPV status, tobacco use, contraceptive used did not alter the results. At median follow-up of 6 months, 85% of subjects have not required LEEP based on routine clinical triage of improving global assessment. There was no statistically significant difference in any outcome between the DIM and placebo group. Conclusion: Oral DIM at 2 mg/kg/day is well tolerated with no significant toxicity. We observed a high rate of clinically significant improvement in confirmed CIN 2 or 3 lesions among both treatment groups in this randomized clinical trial. © 2009 Elsevier Inc. All rights reserved.
Digumarti R.,Nizam's Institute of Medical Sciences |
Sinha S.,Institute of Oncology and Regional Cancer Center |
Nirni S.S.,Indo American Cancer Institute and Research Center |
Patil S.G.,Bangalore Institute of Oncology |
Pedapenki R.M.,King George Hospital
Indian Journal of Cancer | Year: 2014
Background: Patients with hematological malignancies that are highly proliferative and have high tumor burden are at high risk of developing hyperuricemia and tumor lysis syndrome (TLS), spontaneously and while undergoing chemotherapy. Aim: To assess the safety and efficacy of a new generic formulation of recombinant rasburicase in prevention and treatment of malignancy-associated hyperuricemia. Materials and Methods: An open-label, multicenter, phase-III study was conducted on 100 eligible patients with high risk for TLS. Rasburicase was administered 0.2 mg/kg intravenously over 30 min, daily, for 4 days. The outcome measures were percentage of reduction in plasma uric acid at 4 h after rasburicase, plasma uric acid area under the curve (AUC)0-96 h and incidence of adverse events. Results: Eighty eight patients completed the study period of 10 days. After rasburicase administration, there was a 75.3 ± 28.5% of reduction in plasma uric acid at 4 h as compared to baseline. The plasma uric acid AUC 0-96 h was 259.9 ± 215.5 mg/dL h. Safety of rasburicase was assessed on the basis of changes in vitals, hematological, and biochemical parameters from baseline to termination. Except for the plasma uric acid level, there was no significant difference in any of the parameters. Mild to moderate adverse events were reported in 29 patients. Three patients had serious adverse events (SAEs) unrelated to rasburicase. Conclusions: These results demonstrated that recombinant rasburicase that is indigenously developed is effective for prevention and management of hyperuricemia in patients who are at high risk of developing TLS.
Rilotumumab in combination with epirubicin, cisplatin, and capecitabine as first-line treatment for gastric or oesophagogastric junction adenocarcinoma: An open-label, dose de-escalation phase 1b study and a double-blind, randomised phase 2 study
Iveson T.,University of Southampton |
Donehower R.C.,Johns Hopkins Cancer Center |
Davidenko I.,State Institution of Public Health Regional Clinical Oncology Dispensary |
Tjulandin S.,Russian Cancer Research Center |
And 12 more authors.
The Lancet Oncology | Year: 2014
Background: Dysregulation of the hepatocyte growth factor (HGF)/MET pathway promotes tumour growth and metastasis. Rilotumumab is a fully human, monoclonal antibody that neutralises HGF. We aimed to assess the safety, efficacy, biomarkers, and pharmacokinetics of rilotumumab combined with epirubicin, cisplatin, and capecitabine (ECX) in patients with advanced gastric or oesophagogastric junction cancer. Methods: We recruited patients (≥18 years old) with unresectable locally advanced or metastatic gastric or oesophagogastric junction adenocarcinoma, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, who had not received previous systemic therapy, from 43 sites worldwide. Phase 1b was an open-label, dose de-escalation study to identify a safe dose of rilotumumab (initial dose 15 mg/kg intravenously on day 1) plus ECX (epirubicin 50 mg/m2 intravenously on day 1, cisplatin 60 mg/m2 intravenously on day 1, capecitabine 625 mg/m2 twice a day orally on days 1-21, respectively), administered every 3 weeks. The phase 1b primary endpoint was the incidence of dose-limiting toxicities in all phase 1b patients who received at least one dose of rilotumumab and completed the dose-limiting toxicity assessment window (first cycle of therapy). Phase 2 was a double-blind study that randomly assigned patients (1:1:1) using an interactive voice response system to receive rilotumumab 15 mg/kg, rilotumumab 7·5 mg/kg, or placebo, plus ECX (doses as above), stratified by ECOG performance status and disease extent. The phase 2 primary endpoint was progression-free survival (PFS), analysed by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00719550. Findings: Seven of the nine patients enrolled in the phase 1b study received at least one dose of rilotumumab 15 mg/kg, only two of whom had three dose-limiting toxicities: palmar-plantar erythrodysesthesia, cerebral ischaemia, and deep-vein thrombosis. In phase 2, 121 patients were randomly assigned (40 to rilotumumab 15 mg/kg; 42 to rilotumumab 7·5 mg/kg; 39 to placebo). Median PFS was 5·1 months (95% CI 2·9-7·0) in the rilotumumab 15 mg/kg group, 6·8 months (4·5-7·5) in the rilotumumab 7·5 mg/kg group, 5·7 months (4·5-7·0) in both rilotumumab groups combined, and 4·2 months (2·9-4·9) in the placebo group. The hazard ratio for PFS events compared with placebo was 0·69 (80% CI 0·49-0·97; p=0·164) for rilotumumab 15 mg/kg, 0·53 (80% CI 0·38-0·73; p=0·009) for rilotumumab 7·5 mg/kg, and 0·60 (80% CI 0·45-0·79; p=0·016) for combined rilotumumab. Any grade adverse events more common in the combined rilotumumab group than in the placebo group included haematological adverse events (neutropenia in 44 [54%] of 81 patients vs 13 [33%] of 39 patients; anaemia in 32 [40%] vs 11 [28%]; and thrombocytopenia in nine [11%] vs none), peripheral oedema (22 [27%] vs three [8%]), and venous thromboembolism (16 [20%] vs five [13%]). Grade 3-4 adverse events more common with rilotumumab included neutropenia (36 [44%] vs 11 [28%]) and venous thromboembolism (16 [20%] vs four [10%]). Serious adverse events were balanced between groups except for anaemia, which occurred more frequently in the combined rilotumumab group (ten [12%] vs none). Interpretation: Rilotumumab plus ECX had no unexpected safety signals and showed greater activity than placebo plus ECX. A phase 3 study of the combination in MET-positive gastric and oesophagogastric junction cancer is in progress. © 2014 Elsevier Ltd.
Del Priore G.,Cancer Treatment Centers of America |
Del Priore G.,Indiana University |
Gudipudi D.K.,Indo American Cancer Institute and Research Center
Maturitas | Year: 2014
The scientific basis of uterus transplantation has been developing in parallel to other organ transplants throughout the modern period of transplant medicine. Immunosuppression and surgical techniques have been adequate for at least a decade; ethics and society have been less clearly developed. To many observers, it is still unclear if the endeavor is an overall positive or negative. Although scientific and technical challenges have been overcome, the ethical determinations will be a dynamic process while more experience continues to be gained. The most significant experience still lacking is a term gestation. Undoubtedly during a nine-month gestation, unforeseen challenges will test scientific processes and ethical assumptions. Despite dozens of animal experiments and a few animal births, no human birth has occurred to allow any definitive conclusions. © 2013 Elsevier Ireland Ltd.
Bammidi L.S.,Osmania University |
Neerukonda G.N.,The Surgical Center |
Murthy S.,Indo American Cancer Institute and Research Center |
Kanapuram R.D.,Osmania University
International Journal of Gynecological Cancer | Year: 2012
Objective: To determine the alterations of tumor suppressor gene p16INK4A in human ovarian cancers to explore the possibilities of identifying potential minimally invasive markers in blood of the patients, which could help in the clinical practice as a diagnostic and prognostic marker. Methods: Ovarian cancer tissue and corresponding blood samples were collected from patients (n = 50). The promoter methylation and mutation status of p16 gene in blood and ovarian tissue DNA was then assessed using methylation-specific polymerase chain reaction and denaturing high-performance liquid chromatography along with DNA sequencing method. In addition, the protein expression in ovarian cancer tissue samples was detected by immunostaining method using monoclonal antibodies against p16. Results: Methylation of p16 was observed in 56% (28/50) of the cases. The data showed concordance in promoter methylation status of p16 gene between the tumor tissue and the corresponding blood DNA samples of the patients with ovarian cancer. There was a weak statistical agreement (Kendall tau b = +0.31), and a perfect correspondence was observed in 50% of the cases. The p16 mutations were comparatively low, revealing only 2 variations among the samples analyzed. The percentage of protein expression was inversely correlated with the p16 gene promoter methylation. Conclusions: This study demonstrates that the p16 gene plays a role in the progression of human ovarian cancers and the blood DNA methylation of p16 gene promoter region is a weak predictor of tumor tissue methylation status. Copyright © 2012 by IGCS and ESGO.
Sresty N.V.N.M.,Indo American Cancer Institute and Research Center |
Ramanjappa T.,Sri Krishnadevaraya University |
Raju A.K.,Indo American Cancer Institute and Research Center |
Muralidhar K.R.,Indo American Cancer Institute and Research Center |
Sudarshan G.,Indo American Cancer Institute and Research Center
Brachytherapy | Year: 2010
Purpose: Intensity-modulated radiotherapy (IMRT) technique in external beam radiotherapy and interstitial implant brachytherapy (ISBT) play important role in the treatment of head and neck cancers. Both are proved to be highly conformal techniques of radiotherapy. In this study, we investigated whether ISBT can give treatment planning results similar to those of IMRT. Methods and Materials: Fifteen patients with tongue cancer treated with interstitial high-dose-rate brachytherapy were replanned. They were evaluated with the IMRT planning system. Contouring of target volume, including all critical structures was done on the IMRT treatment planning system to closely match implant brachytherapy planning system. Treatment plans were generated after specifying the goals in the prescription. Conformity index and dose to critical organ were calculated and compared between IMRT and ISBT. Planning time was also recorded for both the techniques in all the cases. Results: Very good dose conformity was observed in ISBT, which was almost the same as that in IMRT. Dose to the critical structure was lower in ISBT in all the cases. Planner time was also less in ISBT for more number of cases. Conclusions: Results show that ISBT treatment modality produces equal or superior planning results when compared with IMRT with our optimization techniques. These results encourage us to continue ISBT practice. © 2010 American Brachytherapy Society.
Goyal M.,Indo American Cancer Institute and Research Center |
Kodandapani S.,Indo American Cancer Institute and Research Center |
Sharanabasappa S.,Indo American Cancer Institute and Research Center |
Palanki S.,Indo American Cancer Institute and Research Center
Indian Journal of Medical and Paediatric Oncology | Year: 2010
Mesothelial cell inclusions in lymph nodes are of rare occurrence and can be mistaken as metastatic adenocarcinomas, mesothelioma or sinus histiocytosis. These are usually found in mediastinal and abdominal lymph nodes and are associated with effusions. We report a case of benign mesothelial cell inclusions in cervical lymph nodes, which was associated with chylous effusion, and immunohistochemistry revealed unusual weak cytoplasmic epithelial membrane antigen positivity in the cells.
Goyal M.,Indo American Cancer Institute and Research Center |
Mohammad N.D.,Indo American Cancer Institute and Research Center |
Palanki S.,Indo American Cancer Institute and Research Center |
Vaniawala S.N.,Gene Laboratory
Indian Journal of Medical and Paediatric Oncology | Year: 2010
Primary plasma cell leukemia is a rare form of plasma cell dyscrasia. We present a case which had leukocytosis with numerous circulating plasma cells in the peripheral blood. Flow cytometry revealed an unusual CD117 expression. Free light chain analysis in the serum showed a markedly elevated level of free lambda light chains. Radiography did not reveal any lytic lesions. Fluorescent in-situ hybridization analysis revealed deletion of 13q14.3 and t(4;14)/t(11;14), while the cytogenetic analysis was normal. The patient was given chemotherapy and was subjected to autologous stem cell transplant, after which she is in complete remission till date.
Prasad V.V.T.S.,Indo American Cancer Institute and Research Center |
Kolli P.,Indo American Cancer Institute and Research Center |
Moganti D.,Indo American Cancer Institute and Research Center
Experimental and Therapeutic Medicine | Year: 2011
The overexpression of arachidonyl lipoxygenase-12 (ALOX12) in breast cancer has been reported. Hence, we examined whether a non-synonymous polymorphism of ALOX12 (mRNA, A835G; Gln261Arg) is associated with breast cancer in females. The polymorphism was detected in genomic DNA by PCR-RFLP. The association between the A835G polymorphism and breast cancer risk was measured by odds ratio (OR) with 95% confidence intervals (CIs) using Fisher's exact test, and differences were considered significant at p<0.05. The frequencies of AA (wild-type), GG (homozygous variant) and AG (heterozygous variant) were 59.5, 0.9 and 39.6% in the controls, and 39.3, 2.5 and 58.2% in the breast cancer cases, respectively. the frequency of the AG genotype was higher in the patients compared to the controls (p<0.0014). the frequency of the GG variant was 2.5 and 0.9% in the cancer subjects and controls, respectively. The relative risk of breast cancer was 2 times greater (OR=2.227) at 95% CI when compared to the relative risk of the heterozygous variant. For the GG genotype, the risk was 4 times greater (OR=4.125) at 95% CI than that of the controls, suggesting a positive association of the AG genotype with the occurrence of breast cancer. The frequencies of the polymorphism were different in different populations. The Arg/Gln and Arg/Arg variants were associated with an increased risk of breast cancer, and the frequencies of the variants differed considerably among various populations. The identification of a gene with links to breast cancer may impact screening, diagnosis and drug development.
PubMed | Indiana University and Indo American Cancer Institute and Research Center
Type: Journal Article | Journal: Maturitas | Year: 2014
The scientific basis of uterus transplantation has been developing in parallel to other organ transplants throughout the modern period of transplant medicine. Immunosuppression and surgical techniques have been adequate for at least a decade; ethics and society have been less clearly developed. To many observers, it is still unclear if the endeavor is an overall positive or negative. Although scientific and technical challenges have been overcome, the ethical determinations will be a dynamic process while more experience continues to be gained. The most significant experience still lacking is a term gestation. Undoubtedly during a nine-month gestation, unforeseen challenges will test scientific processes and ethical assumptions. Despite dozens of animal experiments and a few animal births, no human birth has occurred to allow any definitive conclusions.