Effect of catumaxomab treatment in patients with peritoneal carcinomatosis and malignant ascites due to gastrointestinal cancers on survival.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 490-490 ◽  
Author(s):  
M. A. Ströhlein ◽  
M. M. Essing ◽  
M. Hennig ◽  
D. Seimetz ◽  
M. G. Ott ◽  
...  

490 Background: In 2009 the trifunctional antibody catumaxomab was approved for the intraperitoneal (i.p.) treatment of malignant ascites (MA) in EpCAM-positive carcinomas in Europe. Overall survival (OS) results for gastric cancer patients from the pivotal trial showed a significant treatment benefit of catumaxomab in this patient group. We present the results for the gastrointestinal (GI) cancer subgroup from the pivotal trial including long-term survivors. Methods: A total of 86 patients with MA due to GI cancer (gastric, pancreatic, colon, esophagus, rectum carcinoma) were treated with paracentesis plus catumaxomab (59 patients) vs. paracentesis alone (control, 27 patients). The primary endpoint was puncture-free survival; main secondary endpoints were time to next puncture, overall survival and safety parameters. The endpoints were compared between the catumaxomab and the control group using the Kaplan-Meier method and log-rank test. Analyses were performed for the Full Analysis Set (FAS) and the Safety Set (patients who received at least 1 catumaxomab infusion; 95%). Results: For puncture-free survival, a median of 35 days for catumaxomab vs. 14 days for control was observed (p<0.0001, HR: 0.340 with 95 % CI from 0.194 to 0.597, FAS). Time to next puncture resulted in a median of 118 days vs. 15 days (p<0.0001, HR: 0.161 with 95 % CI from 0.069 to 0.378, FAS). Although the study was not powered nor designed for OS, the difference between treatment and control arm was significant for the Safety Set (median: 61 vs. 44 days, p<0.05, HR: 0.553). ADRs were generally mild to moderate, limited to the treatment period and reversible. Conclusions: I.p. catumaxomab is an EMA-approved treatment for patients suffering from malignant ascites. The positive efficacy results were demonstrated in an advanced stage patient population together with a predictable and manageable safety profile. Patients suffering from peritoneal carcinomatosis with malignant ascites due to GI cancers experience a significant survival benefit from i.p. treatment with catumaxomab. [Table: see text]

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14000-e14000 ◽  
Author(s):  
S. Parsons ◽  
M. Hennig ◽  
R. Linke ◽  
A. Klein ◽  
A. Lahr ◽  
...  

e14000 Background: Parsons et al. (ASCO 2008) reported the results of a pivotal phase II/III trial in patients with malignant ascites due to epithelial cancer. Treatment with the trifunctional antibody catumaxomab resulted in a clinically relevant prolongation of puncture-free survival, defined as the time to the next therapeutic puncture or the time to death, whichever occurred first. Malignant ascites is a typical late-stage manifestation of cancer associated with a poor prognosis and survival. Effective treatment options are limited. It is thus of special interest if all patient subgroups derive objective benefit from treatment. Methods: A post-hoc analysis was performed on the 258 patients with epithelial tumors treated with catumaxomab + paracentesis or paracentesis alone (control) in the pivotal trial to investigate any association between the primary endpoint (puncture-free survival) and the primary tumor, metastases, or other prognostic parameters. Results: Puncture-free survival was lower in patients with non-ovarian vs ovarian tumors and those with a poor prognosis (metastases vs no metastases, elderly vs younger, or low vs serum protein level). However, there was always a statistically significant treatment effect for catumaxomab compared with the respective control group (p≤0.0001, log rank test, for all comparisons) (see table). Conclusion: Catumaxomab demonstrated a significant clinical benefit in patients with malignant ascites independent of the primary tumor or other prognostic factors. Therefore, catumaxomab could be considered as a treatment option for patients with a poor prognosis. [Table: see text] [Table: see text]


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 146-146 ◽  
Author(s):  
Andre Delannoy ◽  
Véronique Lhéritier ◽  
Xavier Thomas ◽  
Sylvie Castaigne ◽  
Françoise Rigal-Huguet ◽  
...  

Abstract Ph+ ALL accounts for approximately one third of ALL cases in patients aged 55 years or older. The median survival of older Ph+ ALL patients is one year, with practically no long-term survivors (Blood, 98, Supp1 p319a, 2001). Imatinib has demonstrated remarkable, although transient, activity in relapsed and refractory Ph+ ALL, which prompted the GRAALL to implement a treatment protocol alternating chemotherapy and imatinib in previously untreated elderly patients: ALL patients aged 55 years or older were treated with steroids during one week and Ph+ cases were then offered a specific therapy including an induction treatment with steroids, cyclophosphamide, daunorubicin and vincristine, followed, irrespective of response to induction chemotherapy, by imatinib, 600 mg daily, combined with intermittent steroids during 2 months. Patients in complete response (CR) were then given 10 blocks of alternating chemotherapy, including 2 additional two-month blocks of imatinib, for a total treatment duration of 2 years. Therapy of occult central nervous system leukemia included 5 intrathecal injections of methotrexate and cranial irradiation. Results are compared with those obtained in 21 Ph+ ALL elderly patients treated according to our previous protocol. From January 2003 to November 2004, 30 patients aged 58 to 78 years (median: 65.8 years) were included in the present study. The median follow-up of surviving patients is 15 months. 20/29 assessable patients were in complete response after induction chemotherapy vs 6/21 in the historical controls given similar induction regimen but with no steroids before chemotherapy (p=0.009). Two patients died during induction treatment vs none in the control group. Out of 6 patients alive with disease at completion of induction, 5 were in CR after salvage with imatinib. The projected overall survival is 71% at 1 year vs 43% in the control group (p=0.008, log-rank test). The 1 year projected relapse-free survival is 58% vs 11% (p=0.003) and the projected 1 year event-free survival (defined as failure to obtain a CR, death or relapse) is 57% vs 5% (p&lt;0.0001). In conclusion, the use of imatinib in elderly patients with Ph+ALL is very likely to dramatically improve prognosis, including overall survival. Compared to our previous study, an unexpected high proportion of patients accrued in this study achieved a CR after induction chemotherapy, possibly denoting a beneficial impact of steroids given before starting chemotherapy.


Author(s):  
Ankita Gupta ◽  
Budhi Singh Yadav ◽  
Nagarjun Ballari ◽  
Namrata Das ◽  
Ngangom Robert

Abstract Background: Brain metastases (BM) are common in patients with HER2-positive and triple-negative breast cancer. In this study we aim to report clinical outcomes with LINAC-based stereotactic radiosurgery/radiotherapy (SRS/SRT) for BM in patients of breast cancer. Methods: Clinical and dosimetric records of breast cancer patients treated for BM at our institute between May, 2015 and December, 2019 were retrospectively reviewed. Patients of previously treated or newly diagnosed breast cancer with at least a radiological diagnosis of BM; 1–4 in number, ≤3·5 cm in maximum dimension, with a Karnofsky Performance Score of ≥60 were taken up for treatment with SRS. SRT was generally considered if a tumour was >3·5 cm in diameter, near a critical or eloquent structure, or if the proximity of moderately sized tumours would lead to dose bridging in a single-fraction SRS plan. The median prescribed SRS dose was 15 Gy (range 7–24 Gy) and SRT dose was 27 Gy in 3 fractions. Clinical assessment and MR imaging was done at 6 weeks post-SRS and then every 3 months thereafter. Intracranial progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan–Meier method and subgroups were compared using log rank test. Results: Total, 40 tumours were treated in 31 patients. The median tumour diameter was 2·3 cm (range 1·0–4·6 cm). SRS and SRT were delivered in 27 and 4 patients, respectively. SRS/SRT was given as a boost to whole brain radiotherapy (WBRT) in four patients and as salvage for progression after WBRT in six patients. In general, nine patients underwent prior surgery. The median follow-up was 7·9 months (0·2–34 months). Twenty (64·5%) patients developed local recurrence, 10 (32·3%) patients developed distant intracranial relapse and 7 patients had both local and distant intracranial relapse. The estimated local control at 6 months and 1 year was 48 and 35%, respectively. Median intracranial progression free survival (PFS) was 3·73 months (range 0·2–25 months). Median intracranial PFS was 3·02 months in patients who received SRS alone or as boost after WBRT, while it was 4·27 months in those who received SRS as salvage after WBRT (p = 0·793). No difference in intracranial PFS was observed with or without prior surgery (p = 0·410). Median overall survival (OS) was 21·7 months (range 0·2–34 months) for the entire cohort. Patients who received prior WBRT had a poor OS (13·31 months) as compared to SRS alone (21·4 months; p = 0·699). Conclusion: In patients with BM after breast cancer SRS alone, WBRT + SRS and surgery + SRS had comparable PFS and OS.


2019 ◽  
Vol 29 (9) ◽  
pp. 1355-1360 ◽  
Author(s):  
Giorgio Bogani ◽  
Daniele Vinti ◽  
Ferdinando Murgia ◽  
Valentina Chiappa ◽  
Umberto Leone Roberti Maggiore ◽  
...  

ObjectiveNodal involvement is one of the most important prognostic factors in cervical cancer patients. We aimed to assess the prognostic role in relation to the burden of nodal disease in stage IIICp cervical cancer.MethodsData on all consecutive patients diagnosed with cervical cancer undergoing primary surgery (radical hysterectomy plus lymphadenectomy) or neoadjuvant chemotherapy followed by radical hysterectomy plus lymphadenectomy, between January 1980 and December 2017, were collected in a dedicated database. Exclusion criteria were: (1) consent withdrawal; (2) synchronous malignancies (within 5 years). Survival outcomes were assessed using Kaplan-Meier and Cox models.ResultsOverall, 177 (14.1%) of 1257 patients with cervical cancer were diagnosed with positive lymph nodes. After a median follow-up of 58 (range 4–175) months, 66 (37.3%) and 37 (20.9%) patients developed recurrent disease and died of disease, respectively. Via multivariate analysis, positive para-aortic nodes (HR 2.62, 95% CI 1.12 to 6.11; p=0.025) and the number of positive nodes (HR 1.06, 95% CI 1.02 to 1.11; p=0.002) correlated with worse disease-free survival. Furthermore, the number of positive nodes (HR 1.06, 95% CI 1.01 to 1.12; p=0.021) correlated with worse overall survival. Number of positive nodes (1, 2 or ≥3) strongly correlated with both disease-free survival (p<0.001, log-rank test) and overall survival (p=0.001, log-rank test). Focusing on patients receiving adjuvant radiation and chemotherapy, the number of positive lymph nodes was associated with response to treatment (p<0.001). Median disease-free survival was 100, 42, and 12 months for patients with one, two, or three or more positive lymph node(s), respectively (p<0.001, log-rank test).ConclusionsIn stage IIICp cervical cancer, adjuvant radiation and chemotherapy provides adequate overall survival in patients diagnosed with only one metastatic node, while survival outcomes are poor in patients with two or more metastatic nodes. This highlights the need for innovative treatments in patients with a high burden of lymphatic disease.


2018 ◽  
Vol 29 (4) ◽  
pp. 443-461 ◽  
Author(s):  
Sara Hanaei ◽  
Khashayar Afshari ◽  
Armin Hirbod-Mobarakeh ◽  
Bahram Mohajer ◽  
Delara Amir Dastmalchi ◽  
...  

Abstract Although different immunotherapeutic approaches have been developed for the treatment of glioma, there is a discrepancy between clinical trials limiting their approval as common treatment. So, the current systematic review and meta-analysis were conducted to assess survival and clinical response of specific immunotherapy in patients with glioma. Generally, seven databases were searched to find eligible studies. Controlled clinical trials investigating the efficacy of specific immunotherapy in glioma were found eligible. After data extraction and risk of bias assessment, the data were analyzed based on the level of heterogeneity. Overall, 25 articles with 2964 patients were included. Generally, mean overall survival did not statistically improve in immunotherapy [median difference=1.51; 95% confidence interval (CI)=−0.16–3.17; p=0.08]; however, it was 11.16 months higher in passive immunotherapy (95% CI=5.69–16.64; p<0.0001). One-year overall survival was significantly higher in immunotherapy groups [hazard ratio (HR)=0.69; 95% CI=0.52–0.92; p=0.01]. As the hazard rate in the immunotherapy approach was 0.83 of the control group, 2-year overall survival was significantly higher in immunotherapy (HR=0.83; 95% CI=0.69–0.99; p=0.04). Three-year overall survival was significantly higher in immunotherapy as well (HR=0.67; 95% CI=0.48–0.92; p=0.01). Overall, median progression-free survival was significantly higher in immunotherapy (standard median difference=0.323; 95% CI=0.110–0.536; p=0.003). However, 1-year progression-free survival was not remarkably different between immunotherapy and control groups (HR=0.94; 95% CI=0.74–1.18; p=0.59). Specific immunotherapy demonstrated remarkable improvement in survival of patients with glioma and could be a considerable choice of treatment in the future. Despite the current promising results, further high-quality randomized controlled trials are required to approve immunotherapeutic approaches as the standard of care and the front-line treatment for glioma.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 117-117
Author(s):  
Lin Chen ◽  
Kecheng Zhang ◽  
Zheng Peng ◽  
Bo Wei ◽  
Hongqing Xi ◽  
...  

117 Background: Autologous, tumor-derived heat shock protein Gp96 peptides complexes have shown antitumor potential in various cancers. We conducted the first Phase II trial to evaluate the safety and efficacy of Gp96 vaccination in adjuvant settings for patients with gastric cancer. Methods: Consecutive patients from November 2012 to December 2015 were enrolled. Participants were allocated to the experimental group or control group, receiving Gp96 vaccination plus chemotherapy or chemotherapy alone respectively. The primary endpoints were disease-free survival and toxicity. The secondary outcomes were overall survival and tumor-specific immune responses. Results: Thirty-nine and forty patients received Gp96 vaccination plus chemotherapy and chemotherapy alone in the adjuvant settings respectively. Significant increased tumor-specific immune responses were observed after Gp96 vaccination. There were comparable disease-free survival ( p = 0.413; HR: 0.75; 95% CI: 0.37−1.48) and overall survival ( p = 0.485; HR: 0.68; 95% CI: 0.24−1.96) between experimental group and control group. In subgroup of patients with stage II and stage III gastric cancer, patients who have received Gp96 vaccination had improved disease-free survival compared those who have not ( p = 0.044; HR: 0.45; 95% CI: 0.22−0.96). Gp96 vaccination plus chemotherapy was well tolerated and no Gp96-related serious adverse event has been observed. Conclusions: Gp96 vaccination could elicit tumor-specific immune responses and could be safely used in adjuvant settings combined with chemotherapy. Patients with less aggressive diseases might benefit from Gp96 therapy.


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 488-488 ◽  
Author(s):  
Sukhvinder Johal ◽  
Irene Santi ◽  
Justin Doan ◽  
Saby George

488 Background: Progression-free survival (PFS) is often used as a primary endpoint in oncology clinical trials as a surrogate for overall survival. Traditionally, the Response Evaluation Criteria in Solid Tumors (RECIST) have defined disease progression as a significant increase in the size of tumor lesions and the development of new lesions. However, some patients starting immunotherapy have shown initial increased size of tumor lesions followed by tumor regression, due to the unique mechanism of action of immunotherapies. This initial “pseudo-progression” could be classified inaccurately as disease progression, as evidenced by benefit from the treatment beyond progression approach ( JAMA Oncol 2016). The phase III CheckMate 025 trial of nivolumab versus everolimus in patients with advanced renal cell carcinoma allowed treatment beyond progression if there was investigator-assessed clinical benefit and tolerability. The purpose of our study was to test if treatment duration for an immunotherapy was different from RECIST-defined PFS, and as such, could potentially explain the apparent lack of correlation between RECIST progression and overall survival shown in CheckMate 025. Methods: Using 1-year data from CheckMate 025, Kaplan–Meier methodology was used to estimate the median duration of PFS and time to treatment discontinuation (TTD). Stratified log-rank test was used to assess the difference in treatments. Results: For all patients, the median PFS with nivolumab was 4.6 months (95% CI, 3.7–5.4 months) and median TTD was 6.2 months (95% CI, 5.6–7.7 months). For everolimus, the median PFS was 4.4 months (95% CI, 3.7–5.5 months) and median TTD was 3.9 months (95% CI, 3.7–4.6 months). Conclusions: Patients in CheckMate 025 had significantly longer survival with nivolumab than with everolimus, but with similar PFS. Our analysis demonstrated that while PFS was similar to TTD with everolimus, there was a significant difference between the 2 measures for nivolumab, suggesting that RECIST-defined PFS may not be the proper endpoint to define progression for immunotherapies. Further evaluation of the association of TTD and other immune-related progression endpoints with overall survival is warranted. Clinical trial information: NCT01668784.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17582-e17582
Author(s):  
Daniel Herrero Rivera ◽  
Ignacio Duran ◽  
Laura Marcos Kovandzic ◽  
Javier Puente ◽  
Begona Mellado ◽  
...  

e17582 Background: Cabazitaxel is a semi-synthetic derivative of a natural taxoid approved for the treatment of mCRPC patients (pts) after failure to docetaxel. Despite its proven efficacy, there is variability in the response, progression-free survival (PFS) and overall survival (OS) of pts. Changes in the genetic constitution of the individual such as the SNPs could explain this variability. The aim of this study was to evaluate the impact of certain SNPs in cabazitaxel activity. Methods: Clinical data from 67 mCRPC pts treated with cabazitaxel between March 2011 and October 2016 were collected. DNA was isolated from formalin fixed paraffin-embedded tumor samples. 56 SNPs in 5 genes related with metabolism and/or mechanism of action of cabazitaxel (CYP3A4, CYP3A5, ABCB1, TUBB1, CYP2C8) were chosen based on their Minor Allele Frequency, linkage disequilibrium and information from dbSNP and analyzed by TaqMan OpenArray (Lifetech). The presence/absence of mutant alleles of the selected SNPs was correlated with clinical features, progression free survival (PFS) and overall survival (OS) of prostate cancer. Chi-square test and Kaplan-Meier with log-rank test were used for statistical analyses. Results: The median age was 61 years (range 44-82). 56.7% (n = 38) had a Gleason score ≥8 and 94% had received docetaxel in first line. Type of response to cabazitaxel was associated with median OS (Partial response = 24.35 months, Stable disease = 11.16 months, Progression disease = 5.8 months; p= 0.045). Univariate analysis, showed worsed OS at 1 year for wild type status of SNP rs151352 (OR = 4, 95%CI 1.27-12.58, p= 0.029). In addition, two SNPs (rs11773597, rs1202186) were associated with radiological response to cabazitaxel ( p= 0.031 and p= 0.030 respectively). Other 7 SNPs (rs11773597, rs2235040, rs1045642, rs1419745, rs1202170, rs6949448, rs11572093) were associated ( p<0.05) with Gleason score, pain, PSA doubling time, febrile neutropenia and asthenia. Conclusions: A particular SNP profile could be predictive of efficacy and related with toxicity in mCRPC population treated with cabazitaxel after progression to docetaxel. These outcomes become particularly relevant in patient selection given the recent results of the CARD trial.


2015 ◽  
Vol 97 (3) ◽  
pp. 215-220 ◽  
Author(s):  
Y Li ◽  
X Meng

Introduction Although it has now been accepted that imatinib is a valid treatment for gastrointestinal stromal tumour (GIST) patients in the adjuvant setting, information on its clinical efficacy in improving the prognosis for patients with colorectal GISTs is limited. Methods The clinical and follow-up records of 42 colorectal GIST patients who underwent surgical resection at our institution between January 2004 and December 2013 were reviewed retrospectively. The effect of postoperative imatinib treatment on recurrence free survival and overall survival time was analysed with the Kaplan–Meier method and the multivariate Cox proportional hazards model. Results Sixteen patients were assigned to imatinib treatment (imatinib group) after surgical tumour resection while twenty-six patients did not receive any adjuvant treatment (control group). The one, three and five-year recurrence free survival rates were 100%, 90% and 77% respectively. This was significantly higher than in the control group (92%, 53% and 36%) (logrank test, p=0.012). The one, three and five-year overall survival rates were 100%, 91% and 68% in the imatinib group compared with 96%, 77% and 39% in the control group (logrank test, p=0.021). Analysis with the multivariate Cox regression model yielded similar results on the efficacy of adjuvant imatinib in prolonging both recurrence free survival (hazard ratio [HR]: 0.23, 95% confidence interval [CI]: 0.07–0.80) and overall survival (HR: 0.20, 95% CI: 0.05–0.91). Conclusions Adjuvant imatinib therapy seems to be effective in decreasing the risk of tumour occurrence and prolonging the overall survival time in colorectal GIST patients.


2020 ◽  
Vol 10 (3) ◽  
pp. 183-189
Author(s):  
Sh. Kh. Gantsev ◽  
O. N. Lipatov ◽  
K. V. Menshikov ◽  
D. S. Tursumetov ◽  
Kh. S. Saydulaeva

Introduction. Hepatocellular carcinoma (HCC) is the most common primary malignant neoplasm of the liver. During the early stages, HCC is asymptomatic, which makes X-ray examination a particularly important diagnostic tool. According to WHO data, the mortality rate from HCC was 782,000 in 2018. HCC is associated with a number of risk factors: a high viral load, liver cirrhosis, detected HBeAg and elevated serum HBsAg levels. Inhibitors of tyrosine kinase receptors increase the overall survival and progression-free survival rates in patients with metastatic HCC. In this article, we conduct an analysis of results of the REFLECT study obtained for Russian patients by the Republican Clinical Oncological Dispensary, Ufa.Materials and methods. The experimental group included 9 patients (52.9%) receiving Lenvatinib. The control group included 8 patients (47.1%)) underwent therapy with Sorafenib at a dose of 800 mg per day 7 (41.17%) patients had a history of chronic hepatitis, of which hepatitis B and chronic hepatitis C was confirmed in 6 and 1 cases, respectively.Results and discussion. Over the period from 2017 up to the present, progression-free survival was observed in three patients (17.6%), of which 2 and 1 received Lenvatinib and Sorafenib, respectively. Overall survival was 10.5 months. The median overall survival rate in the experimental and control groups was 9.8 and 11.2 months, respectively. These parameters are considered comparable, provided that the sample was small.Conclusions. The use of Lenvatinib demonstrated the efficacy comparable to that of Sorafenib in terms of the overall survival rate in patients with inoperable HCC. Lenvatinib allowed statistically and clinically significant improvement in the progression-free survival and time to progression to be achieved. 


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