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Byline: C. Pragnya, V. Linga, N. Thota, S. Gundeti, R. Digumarti INTRODUCTION: Bortezomib is a novel proteasome inhibitor in myeloma. There is a paucity of data from India regarding the [...]

Byline: R. Digumarti, S. Sinha, S. Nirni, S. Patil, R. Pedapenki Background: Patients with hematological malignancies that are highly proliferative and have high tumor burden are at high risk of [...]

Byline: P. Parikh, K. Prabhash, K. Govind, R. Digumarti, S. Pandit, I. Banerjee, R. Biyani, A. Deshmukh, D. Doval, G. Bhattacharyya, S. Gupta The office of the Drugs Controller General [...]

Byline: S. Rajappa, S. Gundeti, S. Uppalapati, S. Jiwatani, A. Abhyankar, C. Pal, R. Digumarti Background: There is general belief that patients who enrolled on a clinical trial have better [...]

Byline: S. Rajappa, S. Gundeti, M. Talluri, R. Digumarti Background : Lung cancer is an important cause of cancer related deaths worldwide. There are few publications from India on treatment [...]

Introduction: Bortezomib is a novel proteasome inhibitor in myeloma. There is a paucity of data from India regarding the efficacy and tolerance to bortezomib.Materials and Methods: All patients with newly diagnosed multiple myeloma from January 2008 to December 2011 treated with bortezomib as the first-line therapy were studied in a retrospective analysis. The primary end point was the overall rate of response. Secondary end points were the progression free survival (PFS), reversibility of renal compromise and safety of bortezomib.Results: Our study included 41 patients with newly diagnosed myeloma. The overall response to bortezomib was 88.5% (complete response [CR] 31.4%, very good partial response 34.2%, partial response [PR] 22.8%). A renal response (CR renal, PR renal or Minimal Response renal combined) was documented 96.2% patients with initial renal impairment. The median time to the first renal response was 21 days. 17 patients (41.4%) had severe toxicity (Grade 3 and 4). Bortezomib induced peripheral neuropathy (BIPN) was the most common toxicity seen (53.6%) and the most common cause for discontinuation of therapy. At a median follow-up of 9 months, median PFS was not reached.Discussion: The results obtained in our study are comparable with those of established studies on bortezomib. Our patient population has similar responses and renal reversibility patterns. However, they are at an increased susceptibility to BIPN, leading to discontinuation of therapy.Conclusion: Bortezomib as first-line therapy has a good efficacy and safety. [ABSTRACT FROM AUTHOR]

The purpose of this bridging phase I study was to characterize the toxicity, pharmacokinetics, and antitumor effects of a capsule formulation of DRF-1042, a novel camptothecin analog, in refractory solid tumor patients. DRF-1042 was given daily for 5 consecutive days for 2 weeks, repeated every 3 weeks at 81 mg/m(2). Adverse events were monitored following NCI-CTC. Blood samples were processed for bioanalysis using a validated high-performance liquid chromatography method. The pharmacokinetics of lactone and total (lactone + carboxylate) forms was determined on days 1 and 12 using a noncompartmental pharmacokinetic method. Pharmacokinetic data with the capsule formulation were compared with previously reported pharmacokinetic parameters with a suspension formulation. Efficacy was evaluated by applying World Health Organization criteria. Six patients received 10 courses of therapy. Thrombocytopenia and diarrhea were dose-limiting toxicities. The upper limit of the area under the curve of DRF-1042 (lactone and total) with the capsule formulation was higher than a suspension formulation at a similar dose on day 1 (lactone: capsule = 8.53 microMxh, suspension = 5.33 microMxh; total: capsule = 393 microMxh, suspension = 176 microMxh) and day 12 (lactone: capsule = 22.1 microMxh, suspension = 6.1 microMxh; total: capsule = 1302 microMxh, suspension = 309 microMxh). The upper limit of the area under the curve of DRF-1042 (lactone and total) was higher under fed conditions (lactone = 15.9 microMxh, total = 605 microMxh) relative to fasted conditions (lactone = 8.53 microMxh, total = 393 microMxh) on day 1. One patient experienced stable disease. The toxicity and pharmacokinetics of the capsule correlated well with the suspension. The recommended phase II dose is 81 mg/m(2). [ABSTRACT FROM AUTHOR]

The objective of this study was to characterize the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetics, and antitumor effects of DRF-1042, a novel camptothecin analog, in refractory solid tumor patients. DRF-1042 was given for 5 consecutive days for 2 weeks, repeated every 3 weeks at 1.5 to 270 mg/m(2). Adverse events were monitored following NCI-CTC. Pharmacokinetics of lactone and total forms were determined using validated high-performance liquid chromatography (HPLC) and noncompartmental methods. Efficacy was evaluated applying World Health Organization (WHO) criteria. The 1st course was used to determine DLT and MTD. Twenty-five patients received 73 courses of therapy. Myelosuppression and diarrhea were DLTs. MTD was 120 mg/m(2)/day. AUC increased approximately linearly with dose. The t(1/2) for lactone and total forms was 9.9 and 29 hours, respectively. AUCs correlated significantly with nadir leucopenia and grade 4 diarrhea. Two complete responses (CRs) and 2 partial responses (PRs) were observed. In addition, 4 stable diseases were observed. The recommended phase II dose is 80 mg/m(2)/day. [ABSTRACT FROM AUTHOR]

Background: Febrile neutropenia (FN) is common in cancer patients particularly hematologic malignancies due to intensive cytotoxic chemotherapy. It is an important cause of morbidity, mortality and treatment delays. The risk is greater in patients with ANC < 500/ mm3 and increases dramatically in those with ANC < 100/ mm3 and duration of neutropenia more than 1 week. Aims and Objectives: The purpose of this study was to evaluate the incidence, demographic characteristics, clinical profile, mortality, outcome and factors affecting the outcome in patients with febrile neutropenia (FN) admitted at our Center between January 2011 and November 2012. Materials and Methods: All cases of FN admitted in our Institute between January 2011 and November 2012 were analyzed. Data was analyzed using IBM statistic SPSS version 19. Results: A total of 333 episodes of FN were reviewed. Hematologic malignancies accounted for 299 (89.7%) episodes and 88% of all the episodes had grade 4 neutropenia. There was a significant association noted between high serum bilirubin, creatinine and outcome. Isolation of an organism from blood culture, positive findings on chest X-ray and fungal infection was associated with higher mortality . Association between transfusion requirements and outcome was analyzed and it was observed that patients who had multiple component transfusions vs single component ones were at a significantly higher risk of death. There were only 7 deaths noted among the patient population. Conclusion: Leukemias are the leading cause of FN at our Institute. Higher bilirubin, creatinine, chest imaging favoring pneumonia, positive isolates and multiple transfusions had significant association with mortality. Large scale prospective studies are needed to determine the association of preemptive therapy with higher mortality. The outcome of high risk FN in this study is favorable.

Paraneoplastic encephalomyelitis (PEM) is a well-characterized neurological syndrome. Its association with ovarian teratoma is rare. A young lady presented with features suggestive of encephalomyelitis with predominant cerebellar syndrome. Magnetic resonance imaging brain was normal. Cerebrospinal fluid showed lymphocytic pleocytosis. Computerized tomography scan of the pelvis revealed a complex left ovarian cyst. With a clinical diagnosis of PEM she underwent a left salpingo-oopherectomy. This was followed by total recovery of the PEM in two weeks. The histopathology revealed immature teratoma. The interesting feature was the clinicopathological correlation between the finding of fetal cerebellar tissue in the tumor and the PEM with predominant cerebellar features.

BACKGROUND: Pixantrone dimaleate (pixantrone)-a novel aza-anthracenedione-was synthesised to reduce anthracycline-related cardiotoxicity without compromising antitumour efficacy. We aimed to assess the efficacy and safety of pixantrone versus an investigator's choice of a single-agent therapy in heavily pretreated patients with relapsed or refractory aggressive non-Hodgkin lymphoma. METHODS: In this phase 3, multicentre, open-label, randomised trial at 66 hospitals in Europe, India, Russia, South America, the UK, and the USA, patients with histologically confirmed aggressive non-Hodgkin lymphoma who had relapsed after two or more previous chemotherapy regimens were randomly assigned (1:1) by an interactive voice response system to treatment with pixantrone dimaleate (85 mg/m(2) intravenously on days 1, 8, and 15 of a 28-day cycle, for up to six cycles) or to a comparator (vinorelbine, oxaliplatin, ifosfamide, etoposide, mitoxantrone, or gemcitabine) given at prespecified standard doses and schedules. Patients were stratified by region, International Prognostic Index score, and previous stem-cell transplantation. Patients and investigators were not masked to treatment assignment; however, an independent assessment panel was masked. The primary endpoint was the proportion of patients with a complete or unconfirmed complete response in the intention-to-treat (ITT) population at the end of treatment. Primary analyses of efficacy were based on the independent assessment panel's data review. The study is registered at ClinicalTrials.gov, number NCT00088530. FINDINGS: The ITT population comprised 70 patients randomly assigned to the pixantrone group and 70 to the comparator. Five patients (two in the pixantrone group and three in the comparator group) dropped out before receiving their study drug. 14 patients (20·0% [95% CI 11·4-31·3]) who received pixantrone achieved a complete or unconfirmed complete response at end of treatment compared with four patients (5·7% [1·6-14·0]) in the comparator group (p = 0·021). The most common grade 3 or 4 adverse events in patients given pixantrone were uncomplicated, non-cumulative neutropenia (28 [41·2%] of 68 patients vs 13 [19·4%] of 67 patients in the comparator group), leucopenia (16 [23·5%] vs five [7·5%]), and thrombocytopenia (eight [11·8%] vs seven [10·4%]). INTERPRETATION: Pixantrone, given as a single-agent salvage therapy in heavily pretreated patients with relapsed or refractory aggressive non-Hodgkin lymphoma, is efficacious and tolerable. It could be a treatment option for patients whose aggressive non-Hodgkin lymphoma has failed to respond to at least two previous chemotherapy regimens. FUNDING: Cell Therapeutics, Inc. [ABSTRACT FROM AUTHOR]

Purpose: Cisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non-small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting., Patients and Methods: This noninferiority, phase III, randomized study compared the overall survival between treatment arms using a fixed margin method (hazard ratio [HR] < 1.176) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1. Patients received cisplatin 75 mg/m 2 on day 1 and gemcitabine 1,250 mg/m 2 on days 1 and 8 (n = 863) or cisplatin 75 mg/m 2 and pemetrexed 500 mg/m 2 on day 1 (n = 862) every 3 weeks for up to six cycles., Results: Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine (median survival, 10.3 v 10.3 months, respectively; HR = 0.94; 95% CI, 0.84 to 1.05). Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with adenocarcinoma (n = 847; 12.6 v 10.9 months, respectively) and large-cell carcinoma histology (n = 153; 10.4 v 6.7 months, respectively). In contrast, in patients with squamous cell histology, there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed (n = 473; 10.8 v 9.4 months, respectively). For cisplatin/pemetrexed, rates of grade 3 or 4 neutropenia, anemia, and thrombocytopenia ( P ≤ .001); febrile neutropenia ( P = .002); and alopecia ( P < .001) were significantly lower, whereas grade 3 or 4 nausea ( P = .004) was more common., Conclusion: In advanced NSCLC, cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine. This is the first prospective phase III study in NSCLC to show survival differences based on histologic type.

Competing Interests: Leela DigumartiEmployment: NATCO PharmaOther Relationship: NATCO Pharma Raghunadharao DigumartiLeadership: NATCO PharmaHonoraria: NATCO PharmaNo other potential conflicts of interest were reported.

Background: Multiple primary malignancy (MPM) is defined as occurrence of two or more synchronous or metachronous primary malignancies. With the rise in cancer burden and meticulous screening of index primary malignancy (IPM) during treatment, increased incidence of second primary malignancy (SPM) is expected. This study was undertaken with an attempt to analyze the incidence, commonest associations, management strategies, and clinical outcomes of MPM., Materials and Methods: This is an observational retrospective study carried out in a single institute with patients registered between 1 st January 2015 and 31 st August 2019. The International Association of Cancer Registries and International Agency for Research on Cancer (IACR/IARC) definition was used for identification of IPM and SPM. Synchronous SPM was defined as malignancy occurring within 6 months from the diagnosis of IPM., Results: Out of 16,461 registered patients during the study interval, 44 (0.26%) cases were found to have MPM. A total of 31 (70.5%) cases were women and 13 (29.5%) cases were men. Median age at presentation of IPM was 48 years and of SPM was 56 years, with median duration between two primaries being 38 months. Seven patients (15.9%) had synchronous malignancies. Gynecological tumors were the most common site of IPM presentation (n = 14, 31.8%) followed by breast (n = 09, 20.5%) and head and neck tumors (n = 07, 15.9%), respectively. The most common SPM was gynecological tumors (n = 12, 27.3%) followed by gastrointestinal malignancies (n = 10, 23.3%). Curative treatment was offered to 88% of patients with IPM and 70% patients with SPM. At a median follow-up of 365 days, 21 (47.72%) patients were disease free, six (13.6%) died of disease and nine (20.5%) were lost to follow-up., Conclusion: The study emphasizes the importance of detecting SPM as a result of improved diagnostic and screening procedures. Clinicians should be aware of it and offer multidisciplinary management., Competing Interests: None

Objectives: The key component of a comprehensive palliative care (PC) unit is provision of a regular and sustainable home-based PC (HBPC) service. This quality improvement project aimed to plan, organise and sustain a regular HBPC service in a government cancer centre in Southeast India. The aim was to regularise and increase the number of home care visits among the patients identified for HBPC services through sustainable interventions., Materials and Methods: The A3 methodology with its team-based, structured problem-solving approach was the tool used. The situational process map at baseline was followed up with a sequential cause and effect analysis and team discussions to create sustainable and reliable interventions. These included creating the electronic data system for data collection in PC, allocation of resources and implementation of systems to coordinate HBPC services. The roles and ownership to maintain improvement were established by designation and this requirement has been included in the job description to ensure reliability and sustainability., Results: The regularisation of home care services with a consistent increase in the number of home visits from 2/week to over 6/week helped achieve the Specific, Measurable, Achievable, Relevant and Time bound goal. Better documentation, coordination and accountability were also positive outcomes. Working with different departments and teams along the project helped build trust and understanding along with a sound base for collaborative research., Conclusion: The A3 way of problem solving through dialogue and consensus helped to organise HBPC services and this methodology can be extended to other areas in future., Competing Interests: There are no conflicts of interest., (© 2021 Published by Scientific Scholar on behalf of Indian Jounal of Palliative Care.)