Chemotherapy For Solid Malignancies Research Articles

Antimicrobial Susceptibility Pattern of the Blood Stream Infection Isolates in Neutropenic Patients on Chemotherapy for Solid Malignancies

Antimicrobial Susceptibility Pattern of the Blood Stream Infection Isolates in Neutropenic Patients on Chemotherapy for Solid Malignancies

SPIRE \u2013 combining SGI-110 with cisplatin and gemcitabine chemotherapy for solid malignancies including bladder cancer: study protocol for a phase Ib/randomised IIa open label clinical trial

BackgroundUrothelial bladder cancer (UBC) accounts for 10,000 new diagnoses and 5000 deaths annually in the UK (Cancer Research UK, http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/bladder-cancer, Cancer Research UK, Accessed 26 Mar 2018). Cisplatin-based chemotherapy is standard of care therapy for UBC for both palliative first-line treatment of advanced/metastatic disease and radical neoadjuvant treatment of localised muscle invasive bladder cancer. However, cisplatin resistance remains a critical cause of treatment failure and a barrier to therapeutic advance in UBC. Based on supportive pre-clinical data, we hypothesised that DNA methyltransferase inhibition would circumvent cisplatin resistance in UBC and potentially other cancers.MethodsThe addition of SGI-110 (guadecitabine, a DNA methyltransferase inhibitor) to conventional doublet therapy of gemcitabine and cisplatin (GC) is being tested within the phase Ib/IIa SPIRE clinical trial. SPIRE incorporates an initial, modified rolling six-dose escalation phase Ib design of up to 36 patients with advanced solid tumours followed by a 20-patient open-label randomised controlled dose expansion phase IIa component as neoadjuvant treatment for UBC. Patients are being recruited from UK secondary care sites. The dose escalation phase will determine a recommended phase II dose (RP2D, primary endpoint) of SGI-110, by subcutaneous injection, on days 1–5 for combination with GC at conventional doses (cisplatin 70 mg/m2, IV infusion, day 8; gemcitabine 1000 mg/m2, IV infusion, days 8 and 15) in every 21-day cycle. In the dose expansion phase, patients will be randomised 1:1 to GC with or without SGI-110 at the proposed RP2D. Secondary endpoints will include toxicity profiles, SGI-110 pharmacokinetics and pharmacodynamic biomarkers, and pathological complete response rates in the dose expansion phase. Analyses will not be powered for formal statistical comparisons and descriptive statistics will be used to describe rates of toxicity, efficacy and translational endpoints by treatment arm.DiscussionSPIRE will provide evidence for whether SGI-110 in combination with GC chemotherapy is safe and biologically effective prior to future phase II/III trials as a neoadjuvant therapy for UBC and potentially in other cancers treated with GC.Trial RegistrationEudraCT Number: 2015–004062-29 (entered Dec 7, 2015)ISRCTN registry number: 16332228 (registered on Feb 3, 2016)

Prevalence of detectable HBV DNA in cancer patients with resolved HBV infection (HBsAg (-) HBcAb (+) and its evolution after cytotoxic chemotherapy.

194 Background: Reactivation of hepatitis B virus (HBV) has been widely reported in HBsAg+ cancer patients undergoing chemotherapy, mainly in patients with lymphoma and breast cancer who received Rituximab and Adriamycin based chemotherapy. Reactivation of HBV has also been reported in a few patients who had previous exposure and resolved HBV infection (HBsAg-, HBcAb+). However there is no consensus as to whether prophylactic antiviral therapy should be used for this group, or whether the presence HBsAb plays a further protective role. Methods: We retrospectively and prospectively identified cancer patients undergoing chemotherapy who have HBsAg-, HBcAb+ status. Their HBV DNA levels and serial liver functions were followed. We aimed to evaluate the prevalence of detectable HBV DNA and HBV seroconversion rate after chemotherapy. Results: Between 11/2011 to 6/2013, 124 patients were screened and 51 (41%) had pretreatment HBsAg-, HBcAb+ status. Forty two (82%) patients were of Asian descent; 18 (35%) were males and 33 (65%) were females. Median age was 60 years with a range of 28 to 84 years. Forty seven patients (92%) received chemotherapy for solid malignancies while 4 (8%) received rituximab. Only one patient (2%) had detectable HBV DNA prior to treatment and received baraclude for prophylaxis. Fifteen patients (29%) had HBsAg-, HBcAb+, HBsAb- status, 36 (71%) had HBsAg-, HBcAb+, HBsAb+ status. Serial LFTs were followed over a median chemotherapy duration of 4 months (1 to 18 months). 2 had transient increase; 13 showed persistent but stable elevation related to tumor in the liver; 4 patients were tested for HBV DNA at LFT elevation and were negative. No patient had persistent or worsening LFT related to HBV reactivation. Conclusions: The prevalence of HBsAg-,HBcAb+ cancer patients is very high in South Brooklyn, NY, predominantly in Asian patients. Prevalence of detectable baseline HBV DNA is extremely low, even in isolated HbcAb positive patients and there was no seroconversion of HBV during chemotherapy, irrespective of HBsAb status. Prophylactic antiviral therapy is unnecessary.

P2-127 - Pneumocystis Pneumonia in Patients with Solid Tumors during Chemotherapy

ABSTRACT Background Pneumocystis pneumonia (PCP) is an opportunistic infection well recognized in patients with profound T cell immunodeficiency, especially in patients with AIDS. This infection is also a life-threatening complication seen during immunosuppressive chemotherapy for cancer or organ transplantation, so it is important to make an early diagnosis and start treatment. We present three cases of PCP developing during chemotherapy for solid malignancies. Case reports Case 1: A 50-year-old female received a first-line chemotherapy of gemcitabine–docetaxel (GT therapy) for leiomyosarcoma. After three cycles of GT therapy, she was admitted for a non-productive cough and high fever. Her chest radiograph and CT showed diffuse ground-glass bilateral opacities. SpO2 was 90% (room air). Serum b- d -glucan was 66.7 pg/ml. PCR of PCP by using BAL specimens was positive. We diagnosed PCP infection. Case 2: A 70-year-old female received gemcitabine (GEM) monotherapy as a first-line treatment of a pancreas cancer. After two cycles of GEM therapy, she developed dyspnea and a fever of 38°C. Her chest radiograph and CT showed diffuse ground-glass bilateral opacities. SpO2 was 92% (room air). Serum b- d -glucan was 40.8 pg/ml. We diagnosed PCP infection on the basis of these findings. Case 3: A 64-year-old female received neo-adjuvant chemotherapy with 5-fluoropyrimidine, epirubicin and cyclophosphamide (FEC therapy) for a breast cancer. After two cycles of FEC therapy, she was admitted for febrile neutropenia. Although neutropenia was recovered, she developed exertional dyspnea and a non-productive cough with continuous high fever. Her chest CT showed diffuse ground-glass bilateral opacities. SpO2 was 90% (room air). Serum b- d -glucan was 39.5 pg/ml. We diagnosed PCP infection on the basis of these findings. These patients were immediately treated with trimethoprim–sulfamethoxazole (ST) and corticosteroid. The infiltrations and diffuse ground-glass opacities on their chest radiographs improved and they got well. Conclusion We should be careful of not only drug-induced interstitial pneumonia and febrile neutropenia but also PCP during chemotherapy for solid malignancies.

Use of entecavir to prevent hepatitis B virus reactivation during cytotoxic chemotherapy for solid malignancy.

Reactivation of hepatitis B virus (HBV) infection is a frequent complication of cytotoxic chemotherapy that includes steroids. International studies have shown that lamivudine reduces the incidence and severity of hepatitis in HBV carriers undergoing chemotherapy to treat malignancies. However, prolonged lamivudine therapy is associated with an increased risk of drug-resistant tyrosine-methionine-aspartate-aspartate (YMDD) mutations. Here, we studied the role of entecavir in preventing morbidity and mortality associated with HBV reactivation. Three patients with both solid malignancies and hepatitis B surface antigen-positive hepatitis B underwent cytotoxic chemotherapy with steroids. They were followed up for at least 6months after the completion of chemotherapy. The chemotherapeutic regimens comprised carboplatin and paclitaxel for non-small-cell lung cancer, and docetaxel monotherapy or cyclophosphamide plus epirubicin for breast cancer, respectively. All patients completed chemotherapy with steroids without developing severe hepatitis that could be attributable to HBV reactivation. Entecavir prevented the incidence and severity of hepatitis in HBV carriers undergoing chemotherapy for malignancies. Although further studies are required to evaluate whether entecavir can prevent the increased risk of YMDD mutation and decrease the rates of disrupted chemotherapy due to severe hepatitis more effectively than lamivudine, entecavir should be considered before lamivudine for such patients.

Clinical benefits and risks of phase I oncology trials: experience from a single institution

6572 Background: The majority of published series of phase I oncology trials has reported response rates between 4 to 6 percent. A recent meta-analysis of phase I studies showed a higher response rate of 10.6%. Few reports on single-institution phase I experience have been published. Methods: Results from phase I trials conducted at our institution from 1999 to 2007 were reviewed. Data including clinical responses to treatment, toxic events, and treatment-related deaths were recorded. Results: Data from 33 phase I studies [cytotoxic agents (50%), biologic agents (40%), and both (10%)] involving 491 patients (pts) were analyzed. Primary diagnoses included colorectal (25%), ovarian (20%), breast (8.5%), and lung (7%) cancer. 391 pts were assessable for response and the overall response rate (RR) was 8.2% (complete response rate of 1.5%). Patients with documented response had a lower baseline LDH (234 vs 342 U/l, p=0.04), platelet count (167,000 vs 209,000/μl, p=0.03) and serum protein (6.97 vs 7.23 gm/dl, p=0.06) than patients with stable or progressive disease. Notably, patients with a response had a lower mean CTC pain grade while on study (1.1 vs 1.45, p=0.08) than patients with lack of response. Seven of the 32 responses (22%) were observed below the maximum tolerated dose. The rate of stable disease was 39.4%. The mean and median duration on study were 79 days and 53 days, respectively. The treatment-related mortality rate was 1.2%. The rates of hematologic and non-hematologic grade 4 toxic events were 16.7% and 4.3%, respectively. Conclusions: This is one of the largest single-institution series of phase I oncology trials. Our response rate of 8.2% is comparable to that reported in a recently published multi- institution series. This RR falls within the 95% confidence interval of the RR of a majority of third line (and greater) chemotherapy for solid malignancy, and the concept of phase I studies as being ‘non-therapeutic‘ is called into question. No significant financial relationships to disclose.

Comparing the efficacy and safety of fixed versus weight-based dosing of epoetin α in anemic cancer patients receiving platinum-based chemotherapy

Fixed dosing is potentially more convenient than weight-based dosing for both patients and physicians. Therefore, this open-label, randomized (1:1), multicenter study was conducted to compare the effectiveness, safety, and quality-of-life benefits of fixed vs. weight-based dosing of epoetin alpha in anemic cancer patients undergoing chemotherapy. Five hundred forty-six anemic patients undergoing platinum-based chemotherapy for solid malignancies were enrolled. Patients received epoetin alpha, either a fixed dose of 10,000 IU or a weight-based dose of 150 IU/kg, administered subcutaneously 3 times weekly for up to 12 weeks. Endpoints were transfusion requirements over days 29-84, change in hemoglobin (Hb) level from baseline, and change in quality-of-life (QOL) scores from baseline as measured using the Cancer Linear Analog Scale (CLAS). Five hundred and thirty-two patients received at least 1 dose of epoetin alpha, and 510 of these (255 in each treatment group) were considered evaluable for efficacy. At day 84, rates for freedom from transfusion were similar between the fixed-dose and the weight-based dose group (84% vs. 87%, respectively, p=0.32), as calculated by the lifetable method. These rates were also similar between patients in the 45-63 kg weight group receiving the fixed 10,000 IU dose or 7,000-9,000 IU on a per-weight basis (83% vs. 87%, respectively), and those in the 70-100 kg weight group receiving the fixed 10,000 IU dose or 11,000-15,000 IU on a per-weight basis (85% vs. 83%, respectively). Mean Hb increases from baseline to last observation were 2.10 g/dl [95% confidence intervals (CI95) 1.85-2.35] in the 10,000 IU group (from 9.64-11.74 g/dl) and 2.06 g/dl (CI95 1.82-2.30) in the 150 IU/kg group (from 9.70-11.76 g/dl). QOL results were similar for both groups and cumulative data have been reported. For 275 patients (in both groups combined) with CLAS QOL scores both at baseline and 29-98 days thereafter, the QOL index (average of scores for the 3 QOL parameters: energy level, ability to do daily activities and overall QOL) increased by 10.4 mm (CI95 7.5-13.2), from 46.2 mm at baseline to 56.6 mm at the final observation. QOL improvements were directly associated with Hb increases (p<0.001, multiple linear regression analysis) within all chemotherapy response classes. Epoetin alpha was well tolerated in both groups. Fixed (10,000 IU) and weight-based (150 IU/kg) dosing regimens of epoetin alpha demonstrated similar efficacy in maintaining freedom from transfusion, increasing Hb levels, and improving QOL in anemic cancer patients undergoing platinum-based chemotherapy. QOL improvements were directly associated with Hb increases. These findings support the use of a fixed-dose regimen of epoetin alpha, which may offer greater convenience for physicians and patients than weight-based dosing with this agent.

The relationship between self-reported general health and observed depression and anxiety in cancer patients during chemotherapy

In a prospective follow-up study of 30 patients before and during intermittent chemotherapy for solid malignancies, depression and anxiety were assessed with the Hamilton rating scales, and self-reported general health was measured by the General Health Questionnaire (GHQ), Functional Living Index-Cancer (FLIC), and Quality of Life Index (QLI). There were no significant changes in levels of psychopathology or self-reported health after 3 months of chemotherapy, but a significant decrease in Hamilton scores was seen after 6 months among patients responding favorably to chemotherapy. Although states of depression and anxiety occurred in more than 40% of the patients, they were not adequately detected with the GHQ when using the recommended threshold score. Moreover, the commonly used FLIC and QLI were only moderately associated with observer ratings for anxiety and depression. The health-related quality of life concept is discussed, and the risk of neglecting signs of significant psychopathology in cancer p...