Proposed rituximab biosimilar BCD-020 versus reference rituximab for treatment of patients with indolent non-Hodgkin lymphomas: An international multicenter randomized trial.

BCD-020 is a proposed rituximab biosimilar, which has shown high similarity to rituximab in quality and nonclinical studies in vitro and in vivo. International multicenter clinical trial was conducted to compare efficacy and safety of BCD-020 and reference rituximab in adult (older than 18 years) patients with indolent lymphomas (follicular lymphoma grade 1-2, splenic marginal zone lymphoma, and nodal marginal zone lymphoma). Pharmacokinetics, pharmacodynamics, and immunogenicity were also studied. Patients with no previous biologic treatment for lymphoma were randomly assigned 1:1 to receive BCD-020 or comparator 375 mg/m2 for 4 weeks. Primary study outcome was day 50 overall response rate defined as complete or partial remission. Equivalence range was -20% to 20% for 95% CI for overall response rates difference. Secondary outcomes included adverse events, pharmacokinetics, pharmacodynamics, and immunogenicity. One hundred seventy-four patients were enrolled, 89 in BCD-020 arm and 85 in comparator arm. The overall response rate was 44.71% in BCD-020 arm and 41.89% in comparator arm. Limits of 95% confidence interval (CI) for difference of overall response rates between arms were (-12.62%-18.24%) showing equivalent efficacy. Sixty-one (68.54%) and 59 (69.41%) patients had at least one adverse event in BCD-020 arm or comparator arm, respectively. No unexpected adverse reactions were reported. Antidrug antibodies with no neutralizing activity were detected in two patients in comparator arm on day 14 further declining below detection threshold. Rituximab concentrations had equivalent pattern after intravenous administration of both drugs. Both drugs caused depletion of B-cells without significant influence on other blood cell lineages. In this study, we showed equivalent efficacy of BCD-020 and reference rituximab when used in patients with CD20-positive indolent lymphomas. We also confirmed pharmacokinetic equivalence of BCD-020 and reference rituximab. Safety profile, pharmacodynamics, and immunogenicity of BCD-020 were also comparable with those of reference rituximab.

Retraction notice to: Validity of existing CD 4+ classification in North Indians, in predicting immune status [J Infect 51 (2005) 41-46].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). It was brought to the attention of the Editor-in-Chief that large sections of the abstract, methods and results and discussion of the paper are identical to a paper published in The National Medical Journal of India, Volume 14, Issue 6, November/December 2001, Pages 335-339. http://archive.nmji.in/archives/Volume-14/issue-6/original-articles-2.pdf We apologise to the readers of the journal that this plagiarism was not detected during the submission process. To verify originality, all articles submitted to the Journal of Infection are now checked by the originality detection service CrossCheck.

Influence of postoperative complications on relapse-free survival in gastrointestinal malignancies.

OBJECTIVE: A variety of preoperative variables-such as perforation prior to surgery, poor nutritional status, and comorbid conditions such as diabetes-are already known to shorten relapse-free survival in patients with gastrointestinal malignancies. However, the significance of postoperative events in gastrointestinal malignancies is still debated and has not been studied in the population of southern India. METHODS: A retrospective study was conducted at Kidwai Memorial Institute of Oncology, Bangalore, India, from September 2004 to 2006. Patients from a single surgical unit who had undergone surgery with curative intent for gastrointestinal malignancies were evaluated (to maintain uniformity, patients who had undergone palliative surgery were not included in the analysis). We assumed anastomotic leak, delayed wound healing, and postoperative weight loss > 10% as risk factors predictive of poor disease-free survival. These factors were evaluated in all patients, and risk for development of relapse was calculated. RESULTS: A total of 236 patients were evaluated. Baseline parameters were similar in both groups. Compared with patients who developed no postoperative complications, we found that the risk of relapse is 9.8 times greater in patients having anastomotic leak, 8.2 times greater in those with delayed recovery, and 2.3 times greater in those having excessive weight loss. The risk was uniform in all types of gastrointestinal malignancies. CONCLUSION: The results suggest that anastomotic leak, delayed wound healing, and postoperative weight loss in patients with gastrointestinal malignancies confer poor disease-free survival. The presence of these complications warrants closer follow-up and management as appropriate.

Bone metastasis in hepatocellular carcinoma: need for reappraisal of treatment.

Bone is an uncommon site of metastasis in patients with hepatocellular carcinoma (HCC), and often overlooked. We report two cases that had isolated bone metastasis; one of them had prolonged disease-free survival. The present series, along with the literature review, reinforces the idea that HCC should be considered in the differential diagnoses in patients presenting with metastases in bone. The presence of isolated bone metastases need not necessarily indicate poor prognosis, and all such patients need to be offered chemotherapy and at least one of the bone-directed therapies (either local radiation in cases of localized disease or bisphosphonates in the presence of extensive disease) as they may have a better outcome with therapy.

Surgical resection for locally invasive renal cell carcinoma: Is it worthwhile?

BACKGROUND: Many patients with renal cell carcinoma (RCC) present with disease involving the adjacent viscera. Although survival in such patients is poor, surgery remains the only proven modality of treatment. We describe our experience with radical nephrectomy for locally invasive RCC over a five-year period. STUDY DESIGN: A retrospective analysis of the records of all patients who had undergone surgery for locally invasive RCC between January 1999 and December 2004 at our institute. MATERIALS AND METHODS: During the study period, 102 patients with RCC underwent surgery at our institute, out of which 18 (17.6%) patients had adjacent organ involvement. The survival and outcomes in terms of symptom relief are described. STATISTICAL ANALYSIS: The survival rates were calculated by the Kaplan-Meier method using EGRET statistical software package. RESULTS: Of the 18 patients, two patients had inoperable disease. Fifteen out of the 18 patients succumbed to their disease after a median period of 7.5 months. Three patients are still alive, having survived for 13, 16 and 25 months. Most patients derived considerable benefit with respect to relief of symptoms, which was long-lasting. CONCLUSION: For selected patients with locally invasive RCC, radical nephrectomy with en bloc resection of involved organs may provide the opportunity for long-term survival. In others, it may provide considerable symptomatic relief.

Validity of existing CD4+ classification in north Indians, in predicting immune status.

BACKGROUND: The CD4 lymphocyte count had ethnic variability as observed in many studies. In populations with CD4 counts inherently lower than in the West, the Center for Disease Control and Prevention (CDC) classification system of HIV-infected individuals may not be appropriate. As there is no such criterion currently available for ethnic north Indians HIV-patients, we undertook this study to assess the applicability of the western case definition in north Indian HIV patients. METHODS: The CD4 counts of 40 normal and 376 HIV-infected north Indian adults attending to ID clinic, SS hospital, Varanasi were estimated by flowcytometry. The mean CD4 counts were estimated and compared between CDC groups A, B and C and controls. Receiver operator characteristic (ROC) curves were generated to determine the cut-off that correlated best with clinical staging for this population. RESULTS: For CDC groups A, B and C, the mean CD4 counts/mul (upper limits of the 95% CI) were 380.3, 249.2 and 120.9, while the mean CD4 levels in healthy volunteers was 818.4. CONCLUSION: The mean CD4 count among normal north Indians is significantly lower than that in the western population and parallels that of the Chinese. When categorized based on the Center for Disease Control and Prevention (CDC) classification system, the mean CD4 counts in HIV-infected individuals was lower. Categories of CD4 counts >280, 120-280 and < or =120 cells/microl correlate better with disease progression among HIV-infected individuals. A longitudinal study is required before guidelines for the India population can be devised.