Vaccination of renal cell cancer (RCC) patients with modified vaccinia Ankara (MVA) delivering tumor antigen 5T4 administered alone or with interleukin 2 (IL-2) or interferon-alpha (IFN)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3026-3026
Author(s):  
R. Amato ◽  
J. Hernandez-McClain ◽  
R. Harrop ◽  
P. Cen ◽  
G. Doshi
Keyword(s):  
Overall Survival ◽  
Specific Antibody ◽  
Tumor Antigen ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Cell Cancer ◽  
Single Agent ◽  
Interleukin 2 ◽  
Magnetic Resonance Imaging Scan ◽  
Serious Adverse Events

3026 Background: The attenuated vaccinia virus (MVA) has been engineered to deliver the tumor antigen 5T4 (TroVax). More than 90% of RCCs overexpress the 5T4 antigen. A series of clinical trials were conducted to evaluate the effectiveness of MVA 5T4 as a single agent or in combination with either IL-2 or IFN. Methods: Eligibility: Pathologic diagnosis of clear cell or papillary RCC, progressive measurable metastases, any prior therapy, adequate physiological parameters, Karnofsky performance status ≥ 80%, and no active CNS involvement. A regimen of MVA 5T4 alone or in combination with IL-2 or IFN was given. Results: A total of 53 pts received MVA 5T4 alone or in combination with IL-2 or IFN. 13 pts received MVA 5T4 alone, 25 pts received low dose subcutaneous IL-2, and 15 pts received IFN. Clinical responses were assessed by measuring changes in tumor burden via computed tomography or magnetic resonance imaging scan. 5T4-specific cellular and humoral responses were monitored throughout the study. 5T4 was well tolerated with no serious adverse events attributed to vaccination. Of 48 intention-to-treat pts, 43 mounted 5T4-specific antibody responses. 2 pts showed a complete response for > 36 months and 2 other pts had a partial response for > 24 months and 12 months respectively. 20 pts demonstrated disease stabilization for ≥ 3 months. Median progression-free survival and overall survival for all pts was 3.6 months (range 0.8–29.7) and 13.2 months (range 1–38) respectively. A significant relationship was detected between the magnitude of 5T4-specific antibody response and overall survival. Conclusions: 5T4, whether administered alone or in combination, was well tolerated. High frequency of 5T4-specific immune responses and associated enhanced patient survival is encouraging and warrants further investigation. [Table: see text]

Activity of MVA 5T4 alone or in combination with either interleukin-2 (IL-2) or interferon-α (IFN) in patients (Pts) with metastatic renal cell cancer (MRCC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 3069-3069
Author(s):  
A. Cao ◽  
J. Hernandez-McClain ◽  
J. Willis ◽  
R. Harrop ◽  
W. Shingler ◽  
...  
Keyword(s):  
Clear Cell ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Cell Cancer ◽  
Single Agent ◽  
Locally Advanced ◽  
Interleukin 2 ◽  
Future Research ◽  
Interferon Α ◽  
Clinical Activity

3069 Background: MVA 5T4 consists of the highly attenuated modified Vaccinia Ankara virus containing the gene encoding the human TAA 5T4. Ninety percent or more of RCCs overexpress the 5T4 antigen. A series of clinical trials were conducted to evaluate the effectiveness of MVA 5T4 as a single agent or in combination with Interleukin-2 or Interferon Alpha 2B. Methods: Eligibility: pathologic diagnosis of clear cell or papillary RCC, progressive measurable metastases, any prior therapy, adequate physiologic parameters, Karnofsky performance status (KPS) = 80%, and no active CNS involvement. A regimen of MVA 5T4 alone or in combination with IFN or IL-2 was given. Results: A total of 41 patients received MVA 5T4 alone or in combination. 33 patients received MVA 5T4 with low dose IL-2 or IFN. 23 pts had clear cell; 12 papillary; 5 mixed clear cell; and 1 mixed papillary. 19 pts continue to receive therapy. 2 pts (both clear cell RCC) developed complete responses, 3 pts/partial responses (2 clear cell, 1 papillary) 8 pts/stable for 3+months and 6 pts are too early to be staged at this time. Median duration of therapy is 3.0+ (1+-13+) months. Conclusion: Although comparable antibody response were observed in papillary and clear cell histotypes, clear cell patients appeared to be more likely to respond in terms of clinical benefit parameters, to be presented. Of note is that preliminary analysis of clear cell patients suggests a relationship between the anti-5T4 immune response and tumor response. With the immunological potency and encouraging clinical activity, the future research will focus on the phase 3 randomized, double-blind, placebo controlled parallel group study to investigate whether MVA 5T4, added to first line standard of care therapy, prolongs the survival of patients with locally advanced or metastatic clear cell as well as studies to further optimize MVA 5T4 potency. [Table: see text]

Phase II study of single-agent gemcitabine in previously untreated patients with metastatic urothelial cancer.

1997 ◽  
Vol 15 (11) ◽  
pp. 3394-3398 ◽  
Author(s):  
W M Stadler ◽  
T Kuzel ◽  
B Roth ◽  
D Raghavan ◽  
F A Dorr
Keyword(s):  
Karnofsky Performance Status ◽  
Performance Status ◽  
Cell Cancer ◽  
Single Agent ◽  
Transitional Cell ◽  
Significant Activity ◽  
Survival Times ◽  
Metastatic Urothelial Cancer ◽  
Transitional Cell Cancer ◽  
Grade 3

PURPOSE To determine the activity of single-agent gemcitabine in previously untreated patients with metastatic transitional cell cancer. METHODS Forty patients with measurable disease and a Karnofsky performance status > or = 60% were enrolled at five institutions between March 1994 and October 1995. Treatment consisted of gemcitabine (1,200 mg/m2) administered weekly times three on a 4-week cycle. One patient was ineligible for response evaluation because pathology review showed a metastatic melanoma. Responses were confirmed by all investigators and an independent radiologist and were maintained for at least 4 weeks. RESULTS There were four complete and seven partial responses, for an overall response rate of 28%. Responses were seen at all sites, including liver. Median progression-free and overall survival times were 20 and 54 weeks, respectively. Toxicity was mild, with only two grade 4 toxicities. Twenty-five percent of patients experienced grade 3 neutropenia or thrombocytopenia that was rapidly reversible. CONCLUSION Gemcitabine exhibits significant activity in metastatic transitional cell cancer with minimal toxicity, but survival remains short. Trials of gemcitabine in combination with other active agents are thus suggested.

scholarly journals Randomized Study of High-Dose and Low-Dose Interleukin-2 in Patients With Metastatic Renal Cancer

2003 ◽  
Vol 21 (16) ◽  
pp. 3127-3132 ◽  
Author(s):  
James C. Yang ◽  
Richard M. Sherry ◽  
Seth M. Steinberg ◽  
Suzanne L. Topalian ◽  
Douglas J. Schwartzentruber ◽  
...  
Keyword(s):  
Overall Survival ◽  
Low Dose ◽  
Performance Status ◽  
Randomized Study ◽  
Cell Cancer ◽  
Interleukin 2 ◽  
Complete Response ◽  
High Dose ◽  
Metastatic Renal Cancer ◽  
Survival Difference

Purpose: This three-arm randomized study compares response rates and overall survival of patients with metastatic renal cell cancer (RCC) receiving high-dose or one of two low-dose interleukin-2 (IL-2) regimens. Patients and Methods: Patients with measurable metastatic RCC and a good performance status were randomized to receive either 720,000 U/kg (high-dose [HD]) or 72,000 U/kg (low-dose [LD]), both given by intravenous (IV) bolus every 8 hours. After randomly assigning 117 patients, a third arm of low-dose daily subcutaneous IL-2 was added, and an additional 283 patients were randomly assigned. Results: A total of 156 patients were randomly assigned to HD IV IL-2, and 150 patients to LD IV IL-2. Toxicities were less frequent with LD IV IL-2 (especially hypotension), but there were no IL-2-related deaths in any arm. There was a higher response proportion with HD IV IL-2 (21%) versus LD IV IL-2 (13%; P = .048) but no overall survival difference. The response rate of subcutaneous IL-2 (10%, partial response and complete response) was similar to that of LD IV IL-2, differing from HD IV (P = .033). Response durability and survival in completely responding patients was superior with HD IV compared with LD IV therapy (P = .04). Conclusion: Major tumor regressions, as well as complete responses, were seen with all regimens tested. IL-2 was more clinically active at maximal doses, although this did not produce an overall survival benefit. The immunological factors which constrain the curative potential of IL-2 to only a small percentage of patients need to be further elucidated.

Randomized Phase III Study of Exatecan and Gemcitabine Compared With Gemcitabine Alone in Untreated Advanced Pancreatic Cancer

2006 ◽  
Vol 24 (27) ◽  
pp. 4441-4447 ◽  
Author(s):  
Ghassan K. Abou-Alfa ◽  
Richard Letourneau ◽  
Graydon Harker ◽  
Manuel Modiano ◽  
Herbert Hurwitz ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Single Agent ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Water Soluble ◽  
Phase Iii ◽  
Eligibility Criteria

Purpose Exatecan mesylate is a hexacyclic, water-soluble, topoisomerase-1 inhibitor. Exatecan has single-agent and combination activity with gemcitabine in advanced pancreatic cancer. A multicenter, randomized, phase III trial comparing exatecan plus gemcitabine versus gemcitabine alone in advanced pancreatic cancer was conducted. Patients and Methods Eligibility criteria included Karnofsky performance status ≥ 60%, locally advanced or metastatic pancreatic adenocarcinoma, and no prior chemotherapy. Radiation alone for locally advanced disease was permitted. Patients were randomly assigned on a 1:1 basis. For the exatecan plus gemcitabine arm, exatecan 2.0 mg/m2 and gemcitabine 1,000 mg/m2 were administered on days 1 and 8, every 3 weeks. Gemcitabine alone was dosed at 1,000 mg/m2 up to 7 weeks in the first cycle, then once a week for the first 3 weeks of a 4-week cycle. Tumor assessment was performed every 6 weeks. The primary end point was overall survival. An intent-to-treat analysis was used. Results From August 2001 to January 2003, 349 patients were randomly assigned, 175 to exatecan plus gemcitabine and 174 to gemcitabine alone. Twenty-four patients (6.9%) were not treated. The median survival time was 6.7 months for exatecan plus gemcitabine and 6.2 months for gemcitabine alone (P = .52). One complete response (CR; < 1%) and 11 partial responses (PRs; 6.3%) were observed in the exatecan plus gemcitabine treatment group, and one CR (< 1%) and eight PRs (4.6%) were observed in the gemcitabine-alone group. Grade 3 and 4 toxicities were higher for the exatecan plus gemcitabine arm versus the gemcitabine alone arm; neutropenia (30% v 15%) and thrombocytopenia (15% v 4%). Conclusion Exatecan plus gemcitabine was not superior to gemcitabine alone with respect to overall survival in the first-line treatment of advanced pancreatic cancer.

scholarly journals Low cardiac dose and neutrophil-to-lymphocyte ratio predict overall survival in inoperable esophageal squamous cell cancer patients after chemoradiotherapy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu-Chieh Ho ◽  
Yuan-Chun Lai ◽  
Hsuan-Yu Lin ◽  
Ming-Hui Ko ◽  
Sheng-Hung Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cancer Patients ◽  
Squamous Cell ◽  
Squamous Cell Cancer ◽  
Performance Status ◽  
Cell Cancer ◽  
Esophageal Squamous Cell Cancer ◽  
Lymphocyte Ratio ◽  
Cardiac Dose

AbstractWe aimed to determine the prognostic significance of cardiac dose and hematological immunity parameters in esophageal cancer patients after concurrent chemoradiotherapy (CCRT). During 2010–2015, we identified 101 newly diagnosed esophageal squamous cell cancer patients who had completed definitive CCRT. Patients' clinical, dosimetric, and hematological data, including absolute neutrophil count, absolute lymphocyte count, and neutrophil-to-lymphocyte ratio (NLR), at baseline, during, and post-CCRT were analyzed. Cox proportional hazards were calculated to identify potential risk factors for overall survival (OS). Median OS was 13 months (95% confidence interval [CI]: 10.38–15.63). Univariate analysis revealed that male sex, poor performance status, advanced nodal stage, higher percentage of heart receiving 10 Gy (heart V10), and higher NLR (baseline and follow-up) were significantly associated with worse OS. In multivariate analysis, performance status (ECOG 0 & 1 vs. 2; hazard ratio [HR] 3.12, 95% CI 1.30–7.48), heart V10 (> 84% vs. ≤ 84%; HR 2.24, 95% CI 1.26–3.95), baseline NLR (> 3.56 vs. ≤ 3.56; HR 2.36, 95% CI 1.39–4.00), and follow-up NLR (> 7.4 vs. ≤ 7.4; HR 1.95, 95% CI 1.12–3.41) correlated with worse OS. Volume of low cardiac dose and NLR (baseline and follow-up) were associated with worse patient survival.

Impact of ECOG performance status on recurrent/metastatic head and neck squamous cell carcinomas treated with anti-PD1 inhibitors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18004-e18004
Author(s):  
Cameron Chalker ◽  
Vicky Wu ◽  
Jenna M. Voutsinas ◽  
Victoria Hwang ◽  
Christina S Baik ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Outcomes ◽  
Squamous Cell ◽  
Smoking Status ◽  
Demographic Data ◽  
Performance Status ◽  
Univariate Analysis ◽  
Single Agent ◽  
Ecog Performance Status ◽  
Hpv Status

e18004 Background: Anti-PD1 checkpoint inhibitors (ICI) represent an established standard of care for patients with recurrent/metastatic head & neck squamous cell carcinoma (RMHNSCC). Landmark studies excluded patients with ECOG performance status (PS) ≥ 2; the benefit of ICI in this population is therefore unknown. Methods: We retrospectively reviewed RMHNSCC patients who received at least 1 dose of ICI at our institution. Demographic data and clinical outcomes were obtained; the latter included objective response to ICI (ORR), physician-documented CTCAE grade 2+ toxicity (irAE), and any unplanned hospitalization within 100-days of last ICI dose (UH). Associations between demographic data and clinical outcomes were explored using both uni- and multivariate analysis. Overall survival (OS) was estimated using a Cox proportional hazards model; ORR, irAE, and UH were evaluated with logistic regression. This project was approved by our institutional IRB. Results: We identified 152 RMHNSCC patients who were treated with ICI between 1/2013 and 1/2019. ECOG PS was 0 in 42 (27%), 1 in 75 (50%), 2 in 27 (18%), 3 in 2 (1%), and unknown in 6 (4%) patients. The median age was 61 (range: 25 - 90). 124 (82%) were male, 124 (82%) were white, and 69 (45%) were never-smokers. The most common primary sites were the oropharynx (n = 59, 40%), oral cavity (n = 39, 26%), nasopharynx (n = 11, 7%), and larynx (n = 10, 6%). 54 (36%) were p16+ oropharynx cancers. CPS score was available in 10 (6.6%). Single agent ICI was received by 118 (77%) patients. 66 (44%) had a documented irAE and 54 (36%) had an UH. A multivariate model for OS containing PS, smoking status and HPV status showed a strong association between inferior OS and ECOG 2/3 compared to 0/1 (p < 0.001; HR = 3.30, CI = 2.01-5.41), as well as former (vs. never) smoking status (p < 0.001; HR = 2.17, CI = 1.41-3.35). Current smoking (p = 0.25) did not reach statistical significance. On univariate analysis, poor PS was associated with inferior ORR (p = 0.03; OR = 0.25, CI = 0.06-0.77) and increased UH (p = 0.04; OR = 2.43, CI = 1.05—5.71). There was no significant association between irAE and any patient characteristic. Conclusions: We observed inferior overall survival among ICI-treated RMHNSCC patients with ECOG 2/3 in our single-institution, retrospective series. Our findings help frame discussion of therapeutic options in this poor-risk population. Further study must be done to determine which interventions are of greatest benefit for RMHNSCC patients with declining performance status.

Nephrectomy Followed by Interferon Alfa-2b Compared With Interferon Alfa-2b Alone for Metastatic Renal Cell Cancer

2021 ◽  
pp. 113-118
Author(s):  
Christopher Weight
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Performance Status ◽  
Cell Cancer ◽  
Interferon Alfa ◽  
Cytoreductive Nephrectomy

This chapter summarizes the findings of a landmark trial of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma performed in the interferon era. All enrolled patients had a good performance status. It found overall survival extended by about 3 months in the cytoreductive-nephrectomy-plus-interferon arm versus the interferon-only arm.

scholarly journals P14.120 Phase II study of weekly carboplatin in pretreated adult malignant gliomas

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii97-iii97
Author(s):  
V Villani ◽  
A Pace ◽  
A Vidiri ◽  
A Tanzilli ◽  
F Sperati ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Phase Ii ◽  
Clinical Benefit ◽  
Phase Ii Study ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Single Agent ◽  
Malignant Gliomas ◽  
Recurrent Malignant Glioma ◽  
Eligibility Criteria

Abstract BACKGROUND Patients with relapse of recurrent glioma have a poor outcome and limited treatment options. The aim of this study is to investigate the clinical benefit and tolerability of weekly intravenous administration of carboplatin-based monotherapy in adult glioma patients who had progressed from previous chemotherapy lines based on temozolomide and nitrosoureas MATERIAL AND METHODS This was a single arm, Phase II study. Eligibility criteria included progressive or recurrent malignant glioma after radiotherapy and chemotherapy-based treatments and Karnofsky Performance Status (KPS) > 60. RESULTS Thirty-two patients (median age: 43.5 y) were enrolled to receive weekly carboplatin monotherapy in intravenous mode of administration. The median duration of response was 7.3 months with an overall disease control rate of 31.3%. Median progression-free survival (PFS) was 2.3 months while overall survival (OS) was 5.5 months. Patients achieving clinical benefit exhibited a longer PFS (4.6 vs 1.5 months; p>0.001) and OS (7.9 vs 3.2 months; p=0.041) compared to those not achieving clinical benefit. CONCLUSION Our findings show that single agent, weekly, intravenous carboplatin may have a role in the treatment patients with recurrent malignant glioma

Combination intraventricular chemotherapy for meningeal neoplasia.

1986 ◽  
Vol 4 (1) ◽  
pp. 68-73 ◽  
Author(s):  
L Giannone ◽  
F A Greco ◽  
J D Hainsworth
Keyword(s):  
Karnofsky Performance Status ◽  
Performance Status ◽  
Single Agent ◽  
Transitional Cell ◽  
Response Duration ◽  
Complete Response ◽  
Response To Therapy ◽  
Entire Group ◽  
Intraventricular Chemotherapy ◽  
Wbc Count

Twenty two patients with meningeal neoplasia were treated with biweekly combination intraventricular chemotherapy using methotrexate, cytosine arabinoside, and thiotepa. Patients with the following malignancies were included: breast cancer, ten patients; lung cancer, seven; non-Hodgkin's lymphoma, two; malignant melanoma, one; transitional cell carcinoma of the bladder, one; and malignant glioma, one. Eight of 22 patients (36%) had a Karnofsky performance status of less than 50%. Eleven of 22 patients received radiotherapy to symptomatic areas, and seven received systemic chemotherapy in addition to combination intraventricular therapy. Patients were evaluated for both toxicity and response to therapy. Myelosuppression was the major toxic condition and occurred in 17 of 22 patients (77%). Ten patients (45%) had a nadir WBC count of less than 1000/microL or a platelet count of less than 25,000/microL. No patient achieved a complete response (CR), although nine patients (41%) had partial responses (PRs) lasting 4 to 24 + weeks. Median survival for the entire group was 10 weeks (range, 6 to 24+ weeks). In this small group of patients, simultaneous triple-drug intraventricular chemotherapy caused unacceptable myelosuppression without increasing the response rate, response duration, or survival when compared with single-agent methotrexate and radiotherapy.

Gemcitabine as a Single Agent in the Treatment of Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

1999 ◽  
Vol 17 (12) ◽  
pp. 3786-3792 ◽  
Author(s):  
A. Fosså ◽  
A. Santoro ◽  
W. Hiddemann ◽  
L. Truemper ◽  
N. Niederle ◽  
...  
Keyword(s):  
Partial Response ◽  
Confidence Interval ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Single Agent ◽  
World Health ◽  
Hematologic Toxicity ◽  
Grade 3 ◽  
Health Organization ◽  
Hodgkin's Lymphomas

PURPOSE: A multicenter phase II trial was conducted to evaluate the efficacy and toxicity of gemcitabine in patients with relapsed or refractory aggressive non-Hodgkin's lymphomas (NHL). PATIENTS AND METHODS: Thirty-one patients with B-cell intermediate or high-grade NHL (Working Formulation) were enrolled onto the study. The median age was 61 years, with a Karnofsky performance status of ≤ 80% in 65% of patients. Forty-eight percent had stage III or IV (Ann Arbor Classification) at study entry. Pretreatment consisted of one, two, or three chemotherapeutic regimens in nine, 11, and 11 patients, respectively. Gemcitabine 1,250 mg/m2 was administered intravenously over 30 minutes on days 1, 8, and 15 of a 28-day schedule. RESULTS: Thirty patients were assessable for efficacy, and 31 were assessable for toxicity. No complete responses were observed, but six patients showed a partial response, 11 stable disease, and 13 progressive disease. The overall response rate was 20% (95% confidence interval, 8% to 39%) for assessable patients and 19% (95% confidence interval, 8% to 34%) for the intent-to-treat analysis. The median duration of partial response was 6 months (range, 3.7 to 15+ months). Nonhematologic World Health Organization grade 3 toxicity included hepatic toxicity in four patients and infection in two. Hematologic toxicity was observed as grade 3 anemia in three patients, grade 3 leukopenia in two patients, grade 3/4 neutropenia in two patients, and grade 3/4 thrombocytopenia in six patients. CONCLUSION: The present schedule of gemcitabine displays modest efficacy and mild toxicity in pretreated aggressive NHL.

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