Results from a prospective longitudinal survey of employment and work outcomes in newly diagnosed cancer patients during and after curative-intent chemotherapy: A Wisconsin Oncology Network study.

BACKGROUND: Postcancer work limitations may affect a substantial proportion of patients and contribute to the "financial toxicity" of cancer treatment. The degree and nature of work limitations and employment outcomes are poorly understood for cancer patients, particularly in the immediate period of transition after active treatment. We prospectively examined employment, work ability, and work limitations during and after treatment. METHODS: A total of 120 patients receiving curative therapy who were employed prior to their cancer diagnosis and who intended to work during or after end of treatment (EOT) completed surveys at baseline (pretreatment), EOT, and 3, 6, and 12 months after EOT. Surveys included measures of employment, work ability, and work limitations. Descriptive statistics (frequencies, percentages, means with standard deviations) were calculated. RESULTS: A total of 111 participants completed the baseline survey. On average, participants were 48 years of age and were mostly white (95%) and female (82%) with a diagnosis of breast cancer (69%). Full-time employment decreased during therapy (from 88% to 50%) and returned to near prediagnosis levels by 12-month follow-up (78%). Work-related productivity loss due to health was high during treatment. CONCLUSIONS: This study is the first to report the effects of curative intent cancer therapy on employment, work ability, and work limitations both during and after treatment. Perceived work ability was generally high overall 12 months after EOT, although a minority reported persistent difficulty. A prospective analysis of factors (eg, job type, education, symptoms) most associated with work limitations is underway to assist in identifying at-risk patients.

A phase 2 study of weekly temsirolimus and bortezomib for relapsed or refractory B-cell non-Hodgkin lymphoma: A Wisconsin Oncology Network study.

BACKGROUND: Proteasome inhibitors and mammalian target of rapamycin inhibitors each have activity in various B-cell malignancies and affect distinct cellular pathways. Their combination has demonstrated synergy in vitro and in mouse models. METHODS: The authors conducted a single-arm, phase 2 trial of combined temsirolimus and bortezomib in patients with relapsed and refractory B-cell non-Hodgkin lymphoma (NHL) using a dosing scheme that was previously tested in multiple myeloma. The patients received bortezomib and temsirolimus weekly on days 1, 8, 15, and 22 of a 35-day cycle. RESULTS: Of 39 patients who received treatment, 3 achieved a complete response (7.7%; 95% confidence interval [CI], 1.6%-21%), and 9 had a partial response (PR) (23%; 95% CI, 11%-39%). Thus, the overall response rate (12 of 39 patients) was 31% (95% CI, 17%-48%), and the median progression-free survival was 4.7 months (95% CI, 2.1-7.8 months; 2 months for patients with diffuse large B-cell lymphoma [n = 18], 7.5 months for those with mantle cell lymphoma [n = 7], and 16.5 months for those with follicular lymphoma [n = 9]). Two extensively treated patients with diffuse large B-cell lymphoma achieved a complete response. There were no unexpected toxicities from the combination. CONCLUSIONS: The current results demonstrate that the combination of a mammalian target of rapamycin inhibitor and a proteasome inhibitor is safe and has activity in patients with heavily pretreated B-cell NHL. Further studies with this combination are warranted in specific subtypes of NHL.

Vorinostat and bortezomib as third-line therapy in patients with advanced non-small cell lung cancer: a Wisconsin Oncology Network Phase II study.

INTRODUCTION: The primary objective of this phase II trial was to evaluate the efficacy and tolerability of vorinostat and bortezomib as third-line therapy in advanced non-small cell lung cancer (NSCLC) patients. METHODS: Eligibility criteria included recurrent/metastatic NSCLC, having received 2 prior systemic regimens, and performance status 0-2. Patients took vorinostat 400 mg PO daily days 1-14 and bortezomib 1.3 mg/m2 IV day 1, 4, 8 and 11 in a 21-day cycle. Primary endpoint was 3-month progression free survival (3m-PFS), with a goal of at least 40 % of patients being free of progression at that time point. This study followed a two-stage minimax design. RESULTS: Eighteen patients were enrolled in the first stage. All patients had two prior lines of treatment. Patients received a median of two treatment cycles (range: 1-6) on study. There were no anti-tumor responses; stable disease was observed in 5 patients (27.8 %). Median PFS was 1.5 months, 3m-PFS rate 11.1 %, and median overall survival 4.7 months. The most common grade 3/4 toxicities were thrombocytopenia and fatigue. Two patients who had baseline taxane-related grade 1 peripheral neuropathy developed grade 3 neuropathy. The study was closed at its first interim analysis for lack of efficacy. CONCLUSIONS: Bortezomib and vorinostat displayed minimal anti-tumor activity as third-line therapy in NSCLC. We do not recommend this regimen for further investigation in unselected patients.

Should we start looking at the elderly for human immunodeficiency virus infections? A study of trends of human immunodeficiency virus, hepatitis B virus, and hepatitis C virus in Mumbai, Maharashtra, India.

BACKGROUND: There is limited information on the trends of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) co-infections in India - particularly from private health-care settings. We designed the present research to estimate the prevalence of HIV, HBV, and HCV over a period of 7 years and study the factors associated with them. MATERIALS AND METHODS: The present study is a secondary data analysis of data from the laboratory records of 24,086 individuals who were tested over a period of 7 years (2009-2015). We estimated the proportion and 95% confidence intervals (CIs) for HIV, hepatitis B surface antigen (HBsAg), and HCV antibodies. RESULTS: The overall seroprevalence of HIV was 0.35% (95% CI: 0.27%, 0.44%), HBsAg was 1.65% (95% CI: 1.48%, 1.82%), and HCV was 1.73% (95% CI: 1.56%, 1.90%). The prevalence of HIV among those who were more than 70 years of age was 0.14% (95% CI: 0.04%, 0.32%). The prevalence of HBsAg was highest in those aged 30-39 years (2.27%, 95% CI: 1.74%, 2.92%) (P = 0.008). The prevalence of HIV/HBsAg co-infection was 0.019% (95% CI: 0.005%, 0.050%), HIV/HCV co-infection was 0.005% (95% CI: 0.000, 0.027%), and HBsAg/HCV co-infection was 0.059% (95% CI: 0.030%, 0.102%). We did not encounter even a single case of all the three infections. CONCLUSIONS: HIV infection is relatively high in those who were aged 50 years of more; thus, they need to be included in the National AIDS Control Programme. HIV/HBV/HCV co-infections should be regularly monitored in surveillance programs, and antiretroviral therapy officers and counselors should be trained on the management of HIV in those who are co-infected.

Randomized, double-blinded phase II evaluation of docetaxel with or without doxercalciferol in patients with metastatic, androgen-independent prostate cancer.

PURPOSE: Docetaxel is standard of care for androgen-independent prostate cancer (AIPC). Doxercalciferol (1 alpha-hydroxyvitamin D2) had modest activity in phase I/II trials. Preclinical data support combining vitamin D analogues with docetaxel to treat AIPC. EXPERIMENTAL DESIGN: Chemotherapy-naive men with metastatic AIPC were randomized 1:1 to receive, on a 4-week cycle, docetaxel (35 mg/m2 i.v., days 1, 8, and 15) with or without doxercalciferol (10 microg orally, days 1-28). The primary end point was prostate-specific antigen (PSA) response. Secondary end points were progression-free survival, overall survival, objective response, and toxicity. Survival was analyzed as intent to treat. RESULTS: Seventy patients were randomized. Median follow-up was 17.6 months (range, 3.3-45.2). PSA response rate was 46.7% [95% confidence interval (95% CI), 30-64] in the doxercalciferol arm and 39.4% (95% CI, 25-56) with placebo (P = 0.560). Median progression-free survival in the doxercalciferol arm was 6.17 months (95% CI, 4.20-10.7) versus 6.20 months (95% CI, 4.83-9.07) with placebo (P = 0.764). Median overall survival in the doxercalciferol arm was 17.8 months (95% CI, 14.9-23.6) versus 16.4 months (95% CI, 11.9-23.8) with placebo (P = 0.383). Twenty-four patients in the doxercalciferol arm and 23 in the placebo arm were evaluable for objective response. No complete responses were observed. Partial objective response rate was 12.5% with doxercalciferol versus 8.7% with placebo (P = 0.672). Rate of grade > or =3 toxicity was 46% with doxercalciferol versus 42% with placebo (P = 0.785). CONCLUSIONS: Daily doxercalciferol with weekly docetaxel did not enhance PSA response rate or survival. Toxicity was similar between arms. Despite the disappointing results of this study, other vitamin D analogues remain under active investigation.

Developing a Novel, Sustainable and Beneficial System for the Systematic Management of Hospital Wastes.

INTRODUCTION: India is the 2nd most populated country in the world. Population of India is increasing at a tremendous rate. Proportionately, the numbers of people seeking health care are increasing. In that ratio the quantities of hospital wastes, in wider terms, healthcare wastes that are getting generated is also increasing. Current methods for the safe disposal of healthcare wastes are not able to cope up with the rate of generation of healthcare wastes and moreover are not eco-friendly at all. Due to this, the current rules and regulations regarding the safe disposal of healthcare wastes are getting violated, ultimately leading to improper management of healthcare wastes, posing a serious threat to the environment and to the community. AIM: To develop a novel, sustainable and beneficial system for the systematic management of healthcare wastes utilizing the strategies of waste reduction, waste segregation and recycling of Non Hazardous Hospital Wastes (NHHWs). MATERIALS AND METHODS: Firstly a detailed study of the Healthcare Waste Management System (HCWMS) operational at the Jaslok Hospital and Research Centre was done. A pilot study was then performed. After that, data regarding the generation and management of healthcare wastes in the other healthcare settings was collected and analyzed. Considering all this, a novel, sustainable and beneficial template system for the systematic management of healthcare wastes was proposed. Lastly the possible positive impacts from the implementation of HCWMSs designed using proposed template HCWMS in significant numbers of healthcare establishments was gauged. RESULTS: The healthcare waste management system operational at the Jaslok Hospital and Research Centre was found to be very efficient and provided vital inputs about developing the novel HCWMS. The pilot study was successfully completed generating significant revenue from the hospital's own NHHWs while managing them in an eco-friendly way. The total healthcare waste generation in Maharashtra was approximately estimated at about 2,89,200kg/day of which about 43,380kg/day was Bio-Medical Wastes (BMWs) while about 2,45,820kg/day were the NHHWs. This stresses the need of implementing HCWMSs in Healthcare Establishments (HCEs) based on the proposed novel template of HCWMS. CONCLUSION: The novel template system is proposed in a detailed manner under various heads in the form of a handbook which is scalable upwards or downwards as per the requirement of a HCE. The enormous economic and environmental positive impacts from the implementation of the HCWMSs based on the proposed HCWMS in significant numbers of HCEs were presented numerically, putting light on the necessity and tremendous potential of this field of research.

Electronic brachytherapy as adjuvant therapy for early stage breast cancer: a retrospective analysis.

PURPOSE: This multicenter, retrospective study evaluated treatment and clinical outcomes of patients with early stage breast cancer who received adjuvant high-dose rate (HDR) electronic brachytherapy (EBT) treatment post-lumpectomy using the Axxent(®) EBT system. Dosimetric data from the EBT treatment plans were compared with those based on iridium-192 HDR brachytherapy. MATERIAL AND METHODS: Medical records of 63 patients with early stage breast cancer (Tis, T1a, T1b, T1c, and T2) who were treated post-lumpectomy with EBT alone or in combination with external beam radiation therapy were reviewed. The prescribed EBT dose was 34 Gy (10 fractions over 5 days, 3.4 Gy each) to 1 cm from the balloon surface. Dosimetry data from 12 patients were compared with these of treatment plans using an iridium-192 source prepared for the same 12 patients. RESULTS: The majority of patients (90.5%) were older than 50 years and had one or more risk factors for breast cancer (80.6%). Tumor sizes were 0.1 cm to 3.5 cm (mean 1.3 cm). Median follow-up was 7 months (1 to 18 months) post-EBT. Balloon applicators were implanted 0 to 85 days (mean 13.4 days) post-lumpectomy/re-excision. The most common adverse events were erythema, rash dermatitis, and pain or breast tenderness. No recurrences were reported. Dosimetric analyses demonstrated comparable target coverage, increased high-dose regions, and a significantly reduced dose to the ipsilateral breast and lungs as well as the heart with EBT as compared with the iridium-192 treatment plans. CONCLUSION: This retrospective, multicenter study showed that postsurgical adjuvant radiation therapy for early stage breast cancer can be administered using the EBT system with similar toxicity outcomes to those reported with iridium-192 brachytherapy. EBT offers a convenient, portable, nonisotope alternative to HDR brachytherapy using iridium-192.

Use of electronic brachytherapy to deliver postsurgical adjuvant radiation therapy for endometrial cancer: a retrospective multicenter study.

BACKGROUND: This retrospective, multicenter study evaluated the feasibility and safety of high-dose rate electronic brachytherapy (EBT) as a postsurgical adjuvant radiation therapy for endometrial cancer. METHODS: Medical records were reviewed from 41 patients (age 40-89 years) with endometrial cancer (Federation of International Gynecology and Obstetrics stages IA-IIIC) treated at nine centers between April 2008 and October 2009. Treatment included intracavitary vaginal EBT alone (n = l6) at doses of 18.0-24.0 Gy in 3-4 fractions and EBT in combination with external beam radiation therapy (EBRT, n = 25) at a total radiation dose range of 40.0-80.4 Gy. Doses were prescribed to a depth of 5 mm from the applicator surface and to the upper third (n = 15) and the upper half (n = 26) of the vagina. RESULTS: Median follow-up was 3.8 (range 0.5-12.0) months. All 41 patients received the intended dose of radiation as prescribed. Adverse events occurred in 13 of 41 patients and were mild to moderate (Grade 1-2), consisting primarily of vaginal mucositis, rectal mucosal irritation and discomfort, and temporary dysuria and diarrhea. There were no Grade 3 adverse events in the EBT-only treatment group. One patient, who was being treated with the combination of EBT and EBRT for recurrent endometrial cancer, had a Grade 3 adverse event. No recurrences have been reported to date. CONCLUSION: Electronic brachytherapy provides a feasible treatment option for postoperative adjuvant vaginal brachytherapy as sole radiation therapy and in combination with EBRT for primary endometrial cancer. Early and late toxicities were mild to moderate.

Phase I/II study of vinorelbine and exisulind as first-line treatment of advanced non-small cell lung cancer in patients at least 70 years old: a wisconsin oncology network study.

INTRODUCTION: Exisulind is an apoptotic agent with preclinical activity in non-small cell lung cancer (NSCLC). Vinorelbine is safe and effective in older patients with advanced NSCLC. We assessed these agents together as palliative treatment for older patients with advanced NSCLC. METHODS: Chemotherapy-naive patients >/=70-years-old with stage IIIB-IV NSCLC and a performance status (PS) /=3 neutropenia occurred in 14/30 patients. Two patients experienced neutropenic fever. There were no complete responses, one partial response and 12 patients with stable disease as their best response. The objective response rate was 4.0% (95% CI: 0.1-20.4%). Phase II median time-to-progression was 4.7 months (95% CI: 3.1-9.3 months) and median OS was 9.6 months (95% CI: 6.6-19.1 months). CONCLUSIONS: This combination is safe, seems to have activity in the elderly with advanced NSCLC and a PS

Phase I/II study of gemcitabine and exisulind as second-line therapy in patients with advanced non-small cell lung cancer.

BACKGROUND: The study was designed to evaluate the safety and efficacy of exisulind, a selective apoptotic antineoplastic drug, in combination with gemcitabine as second-line therapy in patients with progressing advanced non-small cell lung cancer. METHODS: Patients whose disease progressed more than 3 months from completion of first-line chemotherapy were eligible for this phase I/II trial. Primary end points were maximally tolerated dose and time to progression. Patients in the phase I portion of the study were treated with gemcitabine (1250 mg/m) in combination with three escalated dose levels of exisulind. Treatment involved six cycles of gemcitabine and exisulind followed by exisulind maintenance. The study was subsequently expanded to phase II. RESULTS: Thirty-nine patients (15 in phase I and 24 in phase II) were treated. The regimen was well tolerated with grade 3 fatigue and grade 3 constipation being dose-limiting toxicities. The maximally tolerated dose was not reached. Dose level 3 of exisulind (250 mg twice daily) in combination with gemcitabine was used for phase II. The overall response rates were 7% (phase I), 17% (phase II), and 13% (all). Median time to progression and median and 1-year survival, respectively, were 3.7 and 9.7 months and 33% (phase I); 4.3 and 9.4 months and 41% (phase II); and 4.1 and 9.4 months and 39% (all). CONCLUSION: Although the study met its primary end point of improving time to progression (more than 4.1 months in phase II), we did not observe a clear survival advantage and thus do not plan to further investigate this schedule of gemcitabine and exisulind.

A phase II trial of gemcitabine, 5-fluorouracil and leucovorin in advanced esophageal carcinoma.

BACKGROUND: The aim of this study was to evaluate the overall response rate, toxicity and overall survival in patients with locally advanced or metastatic esophageal cancer treated with gemcitabine, 5-fluorouracil (5-FU) and leucovorin. PATIENTS AND METHODS: Patients with either adenocarcinoma or squamous cell carcinoma of the esophagus could enroll; however, patients could not have received prior chemotherapy for metastatic disease. Treatment cycles consisted of infusions of all three agents at days 1, 8 and 15, repeated every 28 days. Patients received gemcitabine 1,000, leucovorin 25 and 5-FU 600 mg/m(2). Tumor assessment was performed every 2 cycles. Responses were assessed using the Eastern Cooperative Oncology Group solid tumor response criteria. RESULTS: Thirty-five patients with metastatic or locally advanced esophageal cancer enrolled. One complete response and ten partial responses were observed for an overall response rate of 31.4%. An additional 11 patients had stable disease as their best response. The median survival was 9.8 months with a 1-year survival rate of 37.1%. Toxicity was predominately hematologic, with 58% of patients experiencing grade 3 or 4 neutropenia. CONCLUSION: The combination of gemcitabine, 5-FU and leucovorin had activity in advanced esophageal cancer. Patients tolerated the regimen well, with myelosuppression occurring most commonly. The combination merits further investigation as a treatment for esophageal cancer.