Significant Higher Response Rate Research Articles

Botulinum toxin injections after surgery for Hirschsprung disease: Systematic review and meta-analysis

BACKGROUNDA large proportion of patients with Hirschsprung disease experience persistent obstructive symptoms after corrective surgery. Persistent obstructive symptoms may result in faecal stasis that can develop into Hirschsprung-associated enterocolitis, a potential life-threatening condition. Important treatment to improve faecal passage is internal anal sphincter relaxation using botulinum toxin injections.AIMTo give an overview of all empirical evidence on the effectiveness of botulinum toxin injections in patients with Hirschsprung disease.METHODSA systematic review and meta-analysis was done by searching PubMed, EMBASE and the Cochrane Library, using entry terms related to: (1) Hirschsprung disease; and (2) Botulinum toxin injections. 14 studies representing 278 patients met eligibility criteria. Data that were extracted were proportion of patients with improvement of obstructive symptoms or less enterocolitis after injection, proportion of patients with adverse effects and data on type botulinum toxin, mean dose, average age at first injection and patients with associated syndromes. Random-effects meta-analysis was used to aggregate effects and random-effects meta-regression was used to test for possible confounding factors.RESULTSBotulinum toxin injections are effective in treating obstructive symptoms in on average 66% of patients [event rate (ER) = 0.66, P = 0.004, I2 = 49.5, n = 278 patients]. Type of botulinum toxin, average dose, average age at first injections and proportion of patients with associated syndromes were not predictive for this effect. Mean 7 duration of improvement after one botulinum toxin injections was 6.4 mo and patients needed on average 2.6 procedures. There was a significant higher response rate within one month after botulinum toxin injections compared to more than one month after Botulinum toxin injections (ER = 0.79, vs ER = 0.46, Q = 19.37, P < 0.001). Botulinum toxin injections were not effective in treating enterocolitis (ER 0.58, P = 0.65, I2 = 71.0, n = 52 patients). There were adverse effects in on average 17% of patients (ER = 0.17, P < 0.001, I2 = 52.1, n = 187 patients), varying from temporary incontinence to mild anal pain.CONCLUSIONFindings from this systematic review and meta-analysis indicate that botulinum toxin injections are effective in treating obstructive symptoms and that adverse effects were present, but mild and temporary.

Analysis of short-term efficacy as defined by RECIST and pathological response of neoadjuvant chemotherapy comprised paclitaxel and cisplatin followed by radical surgery in patients with locally advanced cervical cancer: A prospective observational study.

The purpose of this study is to investigate short-term efficacy as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) and pathological response of neoadjuvant chemotherapy (NACT) comprised of paclitaxel and cisplatin (TP) followed by radical surgery in patients with locally advanced cervical cancer (LACC).This is a prospective study involving 61 women with histologically confirmed LACC referred for NACT following radical surgery at Beijing Obstetrics and Gynecology Hospital between April 2013 and January 2015.The efficacy of NACT was evaluated by the RECIST. The total short-term efficacy of NACT was 91.8% (complete remission and partial remission). The cervical invasion ≤1/2 was 82.4% in the complete remission (CR) group, 46.2% in the partial remission (PR) group, and 20% in the stable disease (SD) group. The difference between groups was statistically significant (P = .012). The slides of all surgical specimens were reviewed and classified according to the Tumor Regression Grade (TRG). The good response was defined by good short-term efficacy (RECIST) and the difference between groups was statistically significant (P = .042). The route of administration of NACT is a factor predicting response to NACT. A significant higher response rate (P = .011) and lower chemotherapy-related adverse events (P < .05) were observed in the artery intervention (AI) group compared to those received NACT via intravenous (IV) route. All patients were followed-up to the last day of 2015 with the median follow-up time of 21.5 months for NACT. For the 61 patients referred for NACT in LACC, 2 patients had relapsed and 1 patient died from the disease.The study showed that the NACT comprised TP for LACC treatment had a significant local effect. It could reduce tumor myometrial invasion and regress tumor. The route of administrating NACT is a predicting factor to the NACT response; 2 cycles of NACT of AI treatment to LACC patients would obtain a desired response with low chemotherapy adverse events.

Abstract P3-07-67: Chemosensitivity and endocrine sensitivity predicted by MammaPrint and BluePrint in clinical luminal patients in the prospective NBRST study

Abstract Background Ideally classification by subtype predicts treatment response and overall outcome. BluePrint 80-gene functional molecular subtype is based on mRNA expression (as is intrinsic subtype) associated with intact translation to protein (unlike intrinsic subtype). BluePrint (BP) classifies patients into Luminal, HER2 or Basal-type. Presently subtype is approximated using conventional immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) ("conventional subtype") or assigned by gene expression profiling. The aim of the prospective NBRST study was to compare chemosensitivity as defined by pathological Complete Response (pCR), or endocrine sensitivity as defined by partial response (PR) using 80-gene functional subtype vs. conventional IHC/FISH subtyping. In this analyses we present the results of all IHC/FISH Hormone Receptor (HR) positive/Her2 negative patients. Methods The neo-adjuvant NBRST study enrolled over 1000 US patients between June 2011 and December 2014. Women aged 18–90 with histologically proven breast cancer, who were scheduled to start neo-adjuvant chemotherapy (NCT) or neo-adjuvant endocrine therapy (NET), and who provided written informed consent were included. Additional inclusion criteria were no excision biopsy or axillary dissection, no confirmed distant metastatic disease, and no prior therapy for breast cancer. Treatment was at the discretion of the physician adhering to NCCN approved or other peer-reviewed, established regimens. BluePrint in combination with MammaPrint classifies patients into four molecular subgroups: Luminal A, Luminal B, HER2 and Basal. pCR is defined as T0/isN0 and PR is according to RECIST and defined as at least a 30% decrease in the tumor bed. Results 418 IHC/FISH HR+/Her2- T1-4, N0-3, patients were enrolled (median age 54, range 22-87). MammaPrint and BluePrint (MP/BP) classified 28% as Luminal A, 54% as Luminal B, and 18% as Basal-type. The distribution of locally assessed ER% in BP Luminal tumors was 2% ER 0-10%; 3% ER 11-50%; and 95% ER&amp;gt;50% compared to 45% ER 0-10%; 28% ER 11-50%; and 27% ER &amp;gt;50% in BP Basal tumors. Tumors classified as BP Luminal 370 (89%) received NCT and the overall pCR rate was 9%. There was a significantly higher (p&amp;lt;0.0001) pCR rate of 26% in BP Basal tumors compared to the pCR rate in BP/MP Luminal A and B tumors (3% and 6%). 43 (10%) patients received neo-adjuvant ET and 72% had a PR. Conclusions Molecular subtyping using MammaPrint and BluePrint classified 1 out of 5 pathological luminal patients as BP Basal-type with a significant higher response rate to NCT compared to BP Luminal patients. BP Luminal patients have an excellent partial response rate to NET. Citation Format: Pellicane JV, Whitworth P, Beitsch P, Baron P, Beatty J, Murray MK, Dul CL, Mislowsky AM, Nash CH, Richards PD, Lee LL, Stork-Sloots L, de Snoo F, Untch S, Gittleman M, Akbari S, Rotkis MC. Chemosensitivity and endocrine sensitivity predicted by MammaPrint and BluePrint in clinical luminal patients in the prospective NBRST study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-67.

Aminolevulinic acid-photodynamic therapy of basal cell carcinoma and factors affecting the response to treatment: A clinical trial

Background:Basal cell carcinoma (BCC) is the most common type of skin cancer in humans. Photodynamic therapy (PDT) is a non-invasive therapeutic modality that may be considered as a valuable treatment option for BCC. This study was designed with the aim of evaluating the efficacy of PDT in treatment of BCC and factors that may affect the response rate.Materials and Methods:This clinical trial was conducted on 12 patients (28 BCC lesions) who were treated with aminulevulinic acid (ALA)-PDT, monthly, up to 6 sessions and the clinical response, cosmetic results, and possible side effects were evaluated.Results:The study was performed on 28 BCC lesions from 12 patients. Complete response was achieved in 9 (32.1%) lesions. Complete response rate was higher in younger patients (P < 0.01) and those with smaller lesions (P < 0.001). Superficial type also had significant higher response rate (P < 0.05). Patients with history of radiotherapy for the treatment of tinea capitis in childhood showed less response (P < 0.05). Cosmetic results were excellent or good in 77.5% cases. After 6 months of follow-up, none of the resolved lesions recurred.Conclusion:PDT would be a good therapeutic option in treatment of BCC with acceptable efficacy and low side effects. Younger patients, superficial BCCs, and smaller lesions show better response to ALA-PDT. History of radiotherapy may be associated with a lower response rate.

NSCLC in Louisiana: Thymidylate synthase and pemetrexed therapy.

e18142 Background: To analyze all patients treated for metastatic non-small cell lung cancer (NSCLC) at our institution and identify factors that influence responses and prognosis, including histological subtype, chemotherapy regimen and possibly biomarkers. Methods: Patients with diagnosis of NSCLC were identified by ICD-9 codes using the Institutional Tumor Registry and data was extracted and analyzed. Patient who received pemetrexed as part of their treatment had the specimen stained for thymidylate synthase (TS) expression by immunohistochemistry (IHC). Results: Four hundred and thirty charts were reviewed and 70 identified patients received palliative chemotherapy for metastatic NSCLC at our institution between 2005 and 2007. Median age at diagnosis was 65 years (46-81). Seventy five percent of patients had definitive histology, adenocarcinoma being the most common. The overall response rate (ORR) for first line therapy was 40%, with a median time to progression (TTP) of 5 months. Patients who received either cisplatin or bevacizumab containing regimens appeared to have higher RR and longer TTP. In second line, ORR was 20% and TTP 3 months. Patient who were able to receive combination chemotherapy had higher response rates and longer TTP, as did patients receiving pemetrexed. In these patients, non-squamous histology had significant higher response rates and TS expression by IHC testing is underway to evaluate its potential as a marker for response. Third line chemotherapy and above, even when given to selected patients, was rarely effective. Conclusions: Our data at Ochsner Clinic Foundation appears to correlate with the most recent national data. Efforts should be made in other to identify patient who will respond to specific drugs and TS might be an important predictor of pemetrexed therapy sensitivity. No significant financial relationships to disclose.

Abstract 2757: NT5C2 single nucleotide polymorphisms affects survival and response in de novo AML patients with normal karyotype

Abstract The nucleoside analog cytosine arabinoside (Cytosar®, AraC) is one of the corner stones in the treatment of acute myeloid leukemia (AML). Activated AraC is metabolized to inactive compounds by several intracellular enzymes. The levels of some of these enzymes have been correlated to effect of AraC and clinical outcome in patients with AML. This study was designed to evaluate if single nucleotide polymorphisms (SNPs) in genes coding for enzymes involved in the inactivation of AraC affects the therapeutic response in AML-patients treated with AraC in combination with anthracyclines. Three SNPs were investigated in 96 de novo AML patients with normal karyotype and correlated to response and overall survival. Two SNPs were located in the cytidine deaminase gene (CDA, A79C, rs2072671 and C-451T, rs532545), deaminating and inactivating AraC to its corresponding uridine derivative, AraU. The third SNP (A7G, rs10883841) was in the NT5C2 gene coding for the cytosolic 5′-nucleotidase II (cN-II), responsible for dephosphorylation and hence inactivation of AraC monophosphate. All SNPs were in Hardy-Weinberg equilibrium and the allele frequencies were 34.4, 34.4 and 18.8% for CDA A79C and C-451T, and NT5C2 A7G, respectively. Patients that were wild type (A/A) for NT5C2 A7G were found to have a borderline significant higher response rate (51 complete responders of 60 patients with A/A vs 20 complete responders of 30 with A/G or G/G, p=0.06) and longer survival (median survival 1.66 years compared to 0.87 years, log-rank p=0.08) compared to the rest of the patients. The two CDA SNPs (A79C, C-451T) were found to be in linkage disequilibrium. Although statistically not significant, patients that were found to be homozygous for the alternate genetic variant of the CDA SNP had a shorter survival compared to patients carrying the wild type or heterozygous genetic variants. In conclusion, our findings suggest that certain NT5C2 (cN-II) genotypes might affect the survival after chemotherapy and may provide useful information for treatment strategies, classification and individualized chemotherapy, and eventually used as prognostic marker. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2757.

Leflunomide in juvenile idiopathic arthritis

The gold standard of therapy for patients with juvenile idiopathic arthritis (JIA), previously referred to as juvenile rheumatoid arthritis (JRA), has been methotrexate and, if methotrexate fails, a biological agent. Leflunomide, an oral pyrimidine synthesis inhibitor, has been shown to be well tolerated and effective in both short-term and long-term studies of adult rheumatoid arthritis (RA). This article reviews the current state-of-the-art use of leflunomide in JIA. A Phase Ib study demonstrated that leflunomide is effective in patients who have either failed methotrexate or are intolerant of methotrexate (50% American College Rheumatology [ACR] Pedi 30). Following the encouraging results of this initial study, a large, multicentered comparator study of leflunomide versus methotrexate was performed. This study demonstrated that both drugs had excellent response rates (ACR Pedi 30 rates of 68 and 89%, respectively) although there was a statistically significant higher response rate for methotrexate.

Topotecan and ifosfamide as salvage treatment in advanced ovarian cancer

Objective. The purpose of the study was to evaluate activity and toxicity of the combination of topotecan and ifosfamide as salvage treatment in patients with advanced ovarian cancer refractory to or relapsing after platinum compound-based chemotherapy. Methods. Thirty-nine patients entered the trial. Inclusion criteria were: previous platinum compound-based chemotherapy with or without paclitaxel, age ≤75 years, ECOG PS ≤2, and measurable or evaluable lesions. Treatment consisted of topotecan 1.3 mg/sqm d. 1–3 in combination with ifosfamide 1500 mg/sqm d. 1 and 2 (plus uroprotector MESNA), q. 21 days. Results. All patients had received previous platinum compound-based chemotherapy (carboplatin + paclitaxel in 72% of patients); 15 patients had received a further second-line therapy. Overall, 179 cycles were administered; median number courses/patient was 5 (range: 1–8). Eighteen patients received at least six courses of therapy. All patients were evaluable for toxicity and 38 patients for response. Main toxicities consisted of gr3–4 neutropenia in 25%, gr3 anaemia in 18%, neutropenic fever in four patients; 7 patients required blood transfusion and 26 patients were treated with G-CSF. Dose reduction of both drugs was performed in five patients, and seven patients required 1-week delay for recovery of toxicity. Objective response was observed in 16/39 patients (41%): complete response in six patients and partial response in 10 patients; in further three patients, ≥50% reduction of baseline CA-125 was recorded. Significant higher response rate was observed in platinum-sensitive population (11/15 patients) compared to resistant disease (8/24 patients). Conclusions. Chemotherapy with topotecan and ifosfamide (IT) in pretreated advanced ovarian cancer patients is feasible with moderate toxicity. The potential of the regimen for synergistic drug interactions deserves further evaluations.

Interferon-α and Interferon–γ in Advanced Renal Cell Carcinoma: Treatment Results, Survival, and Prognostic Factors in 81 Patients

Background: Treatment with biological response modifiers such as interferons resulted in reproducible responses in patients with renal cell carcinoma without proved benefit on survival and quality of life. Two trials were conducted to define the efficacy and the benefit on survival of interferons in the treatment of advanced renal cell carcinoma. Patients and Methods: Prospectively, 81 patients were treated subcutaneously (sc.) with interferon-α 2B (IFN-α) or interferon-γ (IFN--y). The first trial was randomized; 30 patients received weekly 200 µg IFN-γ alone, and 30 patients were treated with a combination of IFN-α 2B (3-6 ×106 IU/m² 3 times weekly) and interleukin-2 (IL-2) (4.8-19.2 ×106 IU/m² 5 times weekly) for 6 weeks. In the second trial, 21 patients received IFN-α 2B (10 × 10^-6 IU sc.) combined with gradually escalating doses (15-300 µg sc.) of granulocyte-macrophage colony-stimulating factor (GM-CSF) 3 times weekly for 12 weeks. Results: The overall response proportion was 12% (5 complete and 4 partial responses; CR, PR). In the patient groups treated with IFN-α 2B, the overall response rate increased up to 20%. The median response duration was 10.2 months. The median survival duration was 12.7 months. A univariate statistical analysis on prognostic factors (age, sex, Karnofsky performance status, prior nephrectomy, lung metastases only, treatment regimen) showed that only prior nephrectomy was a significant prognostic factor for survival. Conclusion: Biological response modifiers such as IFN-α or IFN-γ had minimal antitumorigenic activity in patients with renal cell carcinoma. Combination therapies with IFN-α 2B resulted in significant higher response rates, but this did not translate into prolonged survival. Out of these studies only prior nephrectomy was identified as the predictor of long-term survival. Because of these disappointing results the study of new biological response modifiers remains priority.