Comparison of toxicity and survival following intraperitoneal recombinant interleukin-2 for persistent ovarian cancer after platinum: twenty-four-hour versus 7-day infusion.

1997 ◽  
Vol 15 (11) ◽  
pp. 3399-3407 ◽  
Author(s):  
R P Edwards ◽  
W Gooding ◽  
B C Lembersky ◽  
K Colonello ◽  
R Hammond ◽  
...  

PURPOSE To compare the toxicity, pharmacokinetics, and efficacy seen in ovarian cancer patients treated with escalating doses of intraperitoneal (I.P.) interleukin-2 (IL-2) by two different infusion schedules. PATIENTS AND METHODS Forty-five patients were sequentially entered onto a phase I/II study in groups of four at fixed dosage tiers of 6 x 10(4), 6 x 10(5), 6 x 10(6), and 3 x 10(7) IU/m2/d in either of two schedules: (A) intermittent weekly infusions of 24 hours' duration; or (B) alternating continuous 7-day infusions followed by 7-day intervals without therapy. Eligibility criteria included > or = six courses of prior platinum-based chemotherapy and laparotomy-confirmed persistent or recurrent ovarian cancer. RESULTS Forty-one eligible patients received I.P. IL-2 and were assessable for toxicity, but six patients were not assessable for response, which left 35 patients assessable for response. Significant locoregional dose-limiting toxicity was seen with the 7-day infusions (including bowel perforation), with 600,000 IU/m2 as the maximum-tolerated dose (MTD), but catheter infection was the only significant complication seen with the 24-hour infusions, for which an MTD was not established. Among 35 assessable patients, there were six laparotomy-confirmed complete responses (CRs) and three partial responses, for an overall response rate of 25.7% (nine of 35). The median survival time of the cohort was 13.7 months and the overall 5-year survival probability was 13.9%. For the nine patients who demonstrated responses (six on the 24-hour infusion and three on the 7-day infusion), the median survival time has not been reached (range, 27 to 90+ months). CONCLUSION I.P. IL-2 is better tolerated as a weekly infusion as compared with a 7-day infusion and demonstrates evidence of possible long-term efficacy in a modest number of patients. A randomized trial is indicated to determine if the prolonged survival seen in this study is a due to I.P. IL-2 therapy or other factors that cannot be controlled for in a single-arm study.

2002 ◽  
Vol 20 (5) ◽  
pp. 1248-1259 ◽  
Author(s):  
Robert E. Bristow ◽  
Rafael S. Tomacruz ◽  
Deborah K. Armstrong ◽  
Edward L. Trimble ◽  
F. J. Montz

PURPOSE: To evaluate the relative effect of percent maximal cytoreductive surgery and other prognostic variables on survival among cohorts of patients with advanced-stage ovarian carcinoma treated with platinum-based chemotherapy. MATERIALS AND METHODS: Eighty-one cohorts of patients with stage III or IV ovarian carcinoma (6,885 patients) were identified from articles in MEDLINE (1989 through 1998). Linear regression models, with weighted correlation calculations, were used to assess the effects on log median survival time of the proportion of each cohort undergoing maximal cytoreduction, dose-intensity of the platinum compound administered, proportion of patients with stage IV disease, median age, and year of publication. RESULTS: There was a statistically significant positive correlation between percent maximal cytoreduction and log median survival time, and this correlation remained significant after controlling for all other variables (P < .001). Each 10% increase in maximal cytoreduction was associated with a 5.5% increase in median survival time. When actuarial survival was estimated, cohorts with ≤ 25% maximal cytoreduction had a mean weighted median survival time of 22.7 months, whereas cohorts with more than 75% maximal cytoreduction had a mean weighted median survival time of 33.9 months—an increase of 50%. The relationship between platinum dose-intensity and log median survival time was not statistically significant. CONCLUSION: During the platinum era, maximal cytoreduction was one of the most powerful determinants of cohort survival among patients with stage III or IV ovarian carcinoma. Consistent referral of patients with apparent advanced ovarian cancer to expert centers for primary surgery may be the best means currently available for improving overall survival.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14718-e14718
Author(s):  
Andrew Peter Dean ◽  
Prasad Cooray

e14718 Background: Pancreatic cancer has traditionally had few effective chemotherapy options. Recent discovery of the over-expression of SPARC (Secreted Protein Acidic Rich in Cysteine) on the majority of pancreatic cancers suggests possible utility of nab-paclitaxel, (a novel albumin-bound form of paclitaxel) as a treatment option. A small prospective study (ASCO 2009) supported this theory. We sought to retrospectively evaluate the treatment efficacy of nab-paclitaxel with gemcitabine or carboplatin in patients with pancreatic cancer to assess concordance with the previous small prospective study. Methods: Data was collected retrospectively from the medical records of pancreatic cancer patients who presented to the private clinic of two treating oncologists (n = 63) from June 2009 to December 2011 and were treated with nab- paclitaxel in combination with either gemcitabine or carboplatin. Patients were assessed on the basis of changes in serum tumour marker (CA19-9, CEA or CA15-3) and changes in tumour size on radiological imaging. Results: 39 (70%) patients had a biochemical response with a greater than 20% drop in tumour markers. Of these, 30 (94%) showed greater than 70% drop with all responders showing reduction in markers within 6 weeks of starting. The number of patients with biochemically defined disease control was 48 (86%). 36 patients were deceased by the end of the series with median overall survival being 12.9 months. The median survival time from starting nab-paclitaxel for these patients was 7.9 months. Very long survival times (up to 28.1 months following commencement nab-paclitaxel) were also observed in 2 patients at the time of data analysis. The overall disease control rate radiologically was 76.79% (43 of 56). Of the 43 responders, 10 were complete responders, 22 showed partial radiological response and 11 had stable disease. Conclusions: This retrospective case series demonstrates a near doubling of overall median survival time and also an improved response rate in patients on nab-paclitaxel treatment as compared to historical data of other treatment options for pancreatic carcinoma. It further supports Von Hoff’s data from ASCO 2010. Further prospective data is eagerly awaited.


2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Chunjing Jin ◽  
Minfeng Yang ◽  
Xueqiao Han ◽  
Haidan Chu ◽  
Yan Zhang ◽  
...  

AbstractGrowing evidence indicates that the tumor biomarker cytokeratin 19 fragment (CYFRA21-1) is significant for a variety of cancers. However, its role in epithelial ovarian cancer (EOC) has rarely been reported. In this study, a receiver operating characteristic (ROC) curve was utilized to estimate the diagnostic efficiency of CYFRA21-1. The correlation between the CYFRA21-1 level and prognosis was analyzed by Kaplan-Meier survival analysis and univariable and multivariable analyses. The relationship between serum CYFRA21-1 levels and different clinicopathological variables was also analyzed. At the same time, the standard serum marker cancer antigen 125 (CA125) was measured. The results demonstrated that CYFRA21-1 expression was significantly increased in EOC compared with expression in benign ovarian diseases and healthy controls, which was similar to CA125 (P < 0.001). CYFRA21-1 expression was positively correlated with CA125 (r = 0.201; P = 0.0032). CYFRA21-1 expression was significantly correlated with lymph node metastasis and ascites (P < 0.001). Furthermore, the median survival time of EOC patients with high CYFRA21-1 expression was 42 months, compared with 54 months in the low CYFRA21-1 expression patients by Kaplan-Meier analysis (P < 0.05), while the high and low CA125 expression groups had no difference in median survival time. Univariate and multivariate analyses indicated that CYFRA21-1 was a poor prognostic factor associated with overall survival (OS), while CA125 was not. Our study indicates that CYFRA21-1 acts as a good complementary diagnostic biomarker and may be superior to CA125 as a prognostic indicator in EOC.


2003 ◽  
Vol 21 (7) ◽  
pp. 1313-1319 ◽  
Author(s):  
Mace L. Rothenberg ◽  
P.Y. Liu ◽  
Patricia S. Braly ◽  
Sharon P. Wilczynski ◽  
Edward V. Hannigan ◽  
...  

Purpose: The median survival time for women with optimally debulked adenocarcinoma of the ovary treated with intravenous (IV) chemotherapy is 41 to 52 months, and the 2-year survival rate is 65% to 70%. Recent studies evaluating intraperitoneal (IP) chemotherapy have reported a median survival time of 49 to 63 months and 2-year survival rates of 70% to 80%. This phase II trial was undertaken to evaluate the feasibility of and 2-year survival rate achieved by the combination of IP paclitaxel, IP cisplatin, and IV paclitaxel in women with optimally debulked, stage III ovarian cancer. Patients and Methods: Treatment consisted of paclitaxel 135 mg/m2 IV over 24 hours on days 1 to 2, cisplatin 100 mg/m2 IP on day 2, and paclitaxel 60 mg/m2 IP on day 8 administered every 21 days for six cycles. Results: In 68 assessable women with optimal stage III ovarian cancer, the 2-year survival rate was 91%, and the median survival time was 51 months. The 2-year disease-free survival rate was 66%, and median disease-free survival time was 33 months. Ninety-six percent of all patients experienced at least one grade 3 to 4 adverse event during therapy, with the most common events being neutropenia (79%), nausea (50%), vomiting (34%), and fatigue/malaise/lethargy (24%). Seventy-one percent of patients completed all six cycles of IV/IP therapy as planned. Conclusion: Combined IV and IP chemotherapy with cisplatin and paclitaxel is associated with a very promising 2-year survival rate in women with optimally debulked ovarian cancer. The ultimate impact of this approach on overall survival requires further evaluation in a randomized trial setting.


2006 ◽  
Vol 24 (10) ◽  
pp. 1561-1567 ◽  
Author(s):  
William G. Richards ◽  
Lambros Zellos ◽  
Raphael Bueno ◽  
Michael T. Jaklitsch ◽  
Pasi A. Jänne ◽  
...  

Purpose To evaluate morbidity, mortality, maximum-tolerated dose (MTD), and outcome of intraoperative intracavitary hyperthermic cisplatin lavage in patients undergoing pleurectomy for malignant pleural mesothelioma (MPM). Patients and Methods Sixty-one patients were prospectively registered. Forty-four resectable patients with MPM underwent pleurectomy, followed by a 1-hour lavage of the resection cavity with dose-escalated cisplatin (50, 100, 150, 175, 200, 225, and 250 mg/m2) at 42°C and then intravenous sodium thiosulfate (16 g/m2 over 6 hours). Survival estimates were compared using the log-rank test and proportional hazards regression. Results Median age was 71 years (range, 50 to 82 years). Twenty-four patients had epithelial tumors, and 20 had sarcomatous or mixed histology. Postoperative mortality was 11% (five of 44 patients). Dose-limiting renal toxicity occurred at 250 mg/m2, establishing the MTD at 225 mg/m2. Other morbidity included atrial fibrillation (14 of 44 patients, 32%) and deep venous thrombosis (four of 44 patients, 9%). Median survival time of all registered patients was 9 months, and the median survival time of resected patients was 13 months. Survival estimates differed significantly for resectable patients exposed to low doses (50 to 150 mg/m2; n = 9; median, 6 months) versus high doses (175 to 250 mg/m2; n = 35; median, 18 months) of hyperthermic cisplatin (P = .0019); recurrence-free interval also differed significantly (4 v 9 months, respectively; P < .0001). Low dose level (relative risk = 3.418) and nonepithelial histology (relative risk = 2.336) were independent risk factors for poor survival. Twenty patients with epithelial tumors who underwent high-dose cisplatin lavage had a 26-month median survival time. Conclusion Pleurectomy and high-dose intraoperative intracavitary hyperthermic cisplatin lavage is feasible in this patient population with restricted surgical options. An apparent dose-related survival benefit warrants further study.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii49-ii49
Author(s):  
Mingyao Lai ◽  
Juan Li ◽  
Qingjun Hu ◽  
Jiangfen Zhou ◽  
Shaoqun Li ◽  
...  

Abstract OBJECTIVE To retrospectively analyze the therapeutic effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy with concomitant temozolomide alone for pediatric diffuse intrinsic pontine glioma (DIPG), and to evaluate the value of temozolomide in the treatment of pediatric DIPG. METHODS The clinical data of children with confirmed DIPG in Guangdong Sanjiu Brain Hospital between January 1, 2010 and December 30, 2019 were collected. The inclusive criteria included (1) receiving a total radiotherapy dose of 54 Gy in 27 fractions, (2) treated with concomitant temozolomide chemotherapy, and (3) with or without adjuvant temozolomide chemotherapy. RESULTS A total of 82 pediatric patients were eligible for the study, with a median age of 7 years (range 2–16 years). The median follow-up was 8.6 months (range 2–28 months) and the median survival time was 9.4 months. The median survival time of 66 patients treated with radiotherapy with concomitant and adjuvant temozolomide was 9.8 months, longer than 7.5 months of the other 16 patients treated with radiotherapy with concomitant temozolomide alone, with statistical differences (P=0.010). Moreover, bevacizumab and nimotuzumab didn’t bring survival benefits to patients with disease recurrence or progression. Hematological toxicity (Grade IV) was not found. CONCLUSION Radiotherapy with concomitant and adjuvant temozolomide prolongs the survival time of children with DIPG.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chaiwat Tawarungruang ◽  
Narong Khuntikeo ◽  
Nittaya Chamadol ◽  
Vallop Laopaiboon ◽  
Jaruwan Thuanman ◽  
...  

Abstract Background Cholangiocarcinoma (CCA) has been categorized based on tumor location as intrahepatic (ICCA), perihilar (PCCA) or distal (DCCA), and based on the morphology of the tumor of the bile duct as mass forming (MF), periductal infiltrating (PI) or intraductal (ID). To date, there is limited evidence available regarding the survival of CCA among these different anatomical and morphological classifications. This study aimed to evaluate the survival rate and median survival time after curative surgery among CCA patients according to their anatomical and morphological classifications, and to determine the association between these classifications and survival. Methods This study included CCA patients who underwent curative surgery from the Cholangiocarcinoma Screening and Care Program (CASCAP), Northeast Thailand. The anatomical and morphological classifications were based on pathological findings after surgery. Survival rates of CCA and median survival time since the date of CCA surgery and 95% confidence intervals (CI) were calculated. Multiple cox regression was performed to evaluate factors associated with survival which were quantified by hazard ratios (HR) and their 95% CIs. Results Of the 746 CCA patients, 514 had died at the completion of the study which constituted 15,643.6 person-months of data recordings. The incidence rate was 3.3 per 100 patients per month (95% CI: 3.0–3.6), with median survival time of 17.8 months (95% CI: 15.4–20.2), and 5-year survival rate of 24.6% (95% CI: 20.7–28.6). The longest median survival time was 21.8 months (95% CI: 16.3–27.3) while the highest 5-year survival rate of 34.8% (95% CI: 23.8–46.0) occurred in the DCCA group. A combination of anatomical and morphological classifications, PCCA+ID, was associated with the longest median survival time of 40.5 months (95% CI: 17.9–63.0) and the highest 5-year survival rate of 42.6% (95% CI: 25.4–58.9). The ICCA+MF combination was associated with survival (adjusted HR: 1.45; 95% CI: 1.01–2.09; P = 0.013) compared to ICCA+ID patients. Conclusions Among patients receiving surgical treatment, those with PCCA+ID had the highest 5-year survival rate, which was higher than in groups classified by only anatomical characteristics. Additionally, the patients with ICCA+MF tended to have unfavorable surgical outcomes. Showed the highest survival association. Therefore, further investigations into CCA imaging should focus on patients with a combination of anatomical and morphological classifications.


Author(s):  
Dayvion R. Adams ◽  
Andrew J. Golnar ◽  
Sarah A. Hamer ◽  
Michel A. Slotman ◽  
Gabriel L. Hamer

AbstractArthropod vectors are frequently exposed to a diverse assemblage of parasites, but the consequence of these infections on their biology and behavior are poorly understood. We experimentally evaluated whether the ingestion of a common protozoan parasite of avian hosts (Haemoproteus spp.; Haemosporida: Haemoproteidae) impacted the survivorship of Culex quinquefasciatus (Say) (Diptera: Culicidae). Blood was collected from wild northern cardinals (Cardinalis cardinalis) in College Station, Texas, and screened for the presence of Haemoproteus spp. parasites using microscopic and molecular methods. Experimental groups of Cx. quinquefasciatus mosquitoes were offered Haemoproteus-positive cardinal blood through an artificial feeding apparatus, while control groups received Haemoproteus-negative cardinal blood or domestic canary (Serinus canaria domestica) blood. Culex quinquefasciatus mosquitoes exposed to Haemoproteus infected cardinal blood survived significantly fewer days than mosquitoes that ingested Haemoproteus-negative cardinal blood. The survival of mosquitoes fed on positive cardinal blood had a median survival time of 18 days post-exposure and the survival of mosquitoes fed on negative cardinal blood exceeded 50% across the 30 day observation period. Additionally, mosquitoes that fed on canary controls survived significantly fewer days than cardinal negative controls, with canary control mosquitoes having a median survival time of 17 days. This study further supports prior observations that Haemoproteus parasites can be pathogenic to bird-biting mosquitoes, and suggests that Haemoproteus parasites may indirectly suppress the transmission of co-circulating vector-borne pathogens by modulating vector survivorship. Our results also suggest that even in the absence of parasite infection, bloodmeals from different bird species can influence mosquito survivorship.


2019 ◽  
Vol 3 (s1) ◽  
pp. 37-37
Author(s):  
Jo Ellen Wilson ◽  
Sarasota Mihalko ◽  
Stephan Heckers ◽  
Pratik P. Pandharipande ◽  
Timothy D. Girard ◽  
...  

OBJECTIVES/SPECIFIC AIMS: Delirium, a form of acute brain dysfunction, characterized by changes in attention and alertness, is a known independent predictor of mortality in the Intensive Care Unit (ICU). We sought to understand whether catatonia, a more recently recognized form of acute brain dysfunction, is associated with increased 30-day mortality in critically ill older adults. METHODS/STUDY POPULATION: We prospectively enrolled critically ill patients at a single institution who were on a ventilator or in shock and evaluated them daily for delirium using the Confusion Assessment for the ICU and for catatonia using the Bush Francis Catatonia Rating Scale. Coma, was defined as a Richmond Agitation Scale score of −4 or −5. We used the Cox Proportional Hazards model predicting 30-day mortality after adjusting for delirium, coma and catatonia status. RESULTS/ANTICIPATED RESULTS: We enrolled 335 medical, surgical or trauma critically ill patients with 1103 matched delirium and catatonia assessments. Median age was 58 years (IQR: 48 - 67). Main indications for admission to the ICU included: airway disease or protection (32%; N=100) or sepsis and/or shock (25%; N=79. In the unadjusted analysis, regardless of the presence of catatonia, non-delirious individuals have the highest median survival times, while delirious patients have the lowest median survival time. Comparing the absence and presence of catatonia, the presence of catatonia worsens survival (Figure 1). In a time-dependent Cox model, comparing non-delirious individuals, holding catatonia status constant, delirious individuals have 1.72 times the hazards of death (IQR: 1.321, 2.231) while those with coma have 5.48 times the hazards of death (IQR: 4.298, 6.984). For DSM-5 catatonia scores, a 1-unit increase in the score is associated with 1.18 times the hazards of in-hospital mortality. Comparing two individuals with the same delirium status, an individual with a DSM-5 catatonia score of 0 (no catatonia) will have 1.178 times the hazard of death (IQR: 1.086, 1.278), while an individual with a score of 3 catatonia items (catatonia) present will have 1.63 times the hazard of death. DISCUSSION/SIGNIFICANCE OF IMPACT: Non-delirious individuals have the highest median survival times, while those who are comatose have the lowest median survival times after a critical illness, holding catatonia status constant. Comparing the absence and presence of catatonia, the presence of catatonia seems to worsen survival. Those individual who are both comatose and catatonic have the lowest median survival time.


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