Ifosfamide- and cisplatin-containing chemotherapy as first-line salvage therapy in germ cell tumors: response and survival.

1997 ◽  
Vol 15 (7) ◽  
pp. 2559-2563 ◽  
Author(s):  
J A McCaffrey ◽  
M Mazumdar ◽  
D F Bajorin ◽  
G J Bosl ◽  
V Vlamis ◽  
...  
Keyword(s):  
Germ Cell ◽  
Median Survival ◽  
Primary Tumor ◽  
Median Survival Time ◽  
Germ Cell Tumors ◽  
Tumor Site ◽  
First Line ◽  
Primary Tumor Site ◽  
First Line Therapy ◽  
Line Therapy

PURPOSE To evaluate the efficacy and toxicity of ifosfamide- and cisplatin-containing chemotherapy as first-line salvage treatment for patients with germ cell tumors (GCT). PATIENTS AND METHODS Fifty-six patients with advanced GCT resistant to one prior cisplatin-containing regimen were treated with a salvage chemotherapy regimen of ifosfamide, cisplatin, and either vinblastine or etoposide (VeIP/VIP). RESULTS Twenty of 56 (36%) assessable patients achieved a complete response (CR). Thirteen (23%) are alive and continuously free of disease at a median follow-up time of 52 months; the median survival duration was 18 months. Among patients with a testis primary tumor site and a prior CR to first-line therapy, 65% are alive and 41% continuously disease-free, and the median survival time has not been reached. In contrast, for patients with an extragonadal primary tumor or with a testis primary tumor site and an incomplete response (IR) to first-line therapy, 31% are alive and 15% continuously free of disease, with a median survival time of 12 months (P < .03). CONCLUSION Ifosfamide- and cisplatin-containing therapy achieves a durable CR in a minority of patients with resistant GCT as first-line therapy. Patients with a primary testis site who relapsed from a CR to first-line cisplatin therapy have a better prognosis than patients with an extragonadal primary tumor site or an IR to first-line therapy. Risk-directed clinical trials to improve response and survival in both subsets are warranted.

scholarly journals GCT-28. RECURRENCE PATTERN AND SURVIVAL FOR RELAPSED INTRACRANIAL NON-GERMINOMATOUS GERM CELL TUMORS: A SINGLE-INSTITUTION EXPERIENCE

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii333-iii333
Author(s):  
Lei Wen ◽  
Zhaoming Zhou ◽  
Qingjun Hu ◽  
Juan Li ◽  
Mingyao Lai ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
Late Recurrence ◽  
Salvage Chemotherapy ◽  
Recurrence Time ◽  
First Line ◽  
Primary Tumor Site ◽  
First Line Therapy ◽  
Line Therapy

Abstract PURPOSE Intracranial non-germinomatous germ cell tumors (NGGCTs) have lower overall survival than germinoma because relatively higher recurrence usually occurs after first line therapy. METHODS Between January 2003 and December 2018, 111 consecutive patients diagnosed with NGGCTs reviewed. Those who progressed after first line therapy were included in this study. Data of first line treatment, salvage treatment, clinicopathological features and survival were collected and analyzed. RESULTS Totally, thirty patients (30/111, 27.0%) relapsed in our cohort, including 19 patients with accurate relapse information detail, and 11 patients who died of disease progression during follow up but without exact time and site of relapse. The median OS from diagnosis of the disease was 49.2 months (95% CI: 14.1 to 84.3 months) and 3-year OS was 54.3%. Patients who received both CSI and chemotherapy relapsed less than those who received reduced volume of radiotherapy or only CSI or only chemotherapy (22.5% vs. 45.5%, p=0.034). Of 19 patients who had detail information of recurrence time and site, the median time from diagnosis of disease to relapse was 9.5 months (2.2 to 72.1 months). Regarding to recurrence site, most patients relapsed in primary site (10/19, 52.6%) or distant intracranial (6/19, 31.6%). The recurrence site of other 3 patients were spinal (n=1), ventricular (n=1) and peritoneal (n=1). CONCLUSION Protracted follow-up is recommended because late recurrence is not uncommon. Primary tumor site and distant intracranial are the most prevalent relapsed location. Patients who relapsed could benefited from both CSI and salvage chemotherapy.

scholarly journals GERM-01. RECURRENCE PATTERN AND SURVIVAL FOR RELAPSED INTRACRANIAL NON-GERMINOMATOUS GERM CELL TUMORS: A SINGLE-INSTITUTION EXPERIENCE

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i16-i16
Author(s):  
Lei Wen
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
Late Recurrence ◽  
Salvage Chemotherapy ◽  
Recurrence Time ◽  
First Line ◽  
Primary Tumor Site ◽  
First Line Therapy ◽  
Line Therapy

Abstract Purpose Intracranial non-germinomatous germ cell tumors (NGGCTs) have lower overall survival than germinoma because relatively higher recurrence usually occurs after first line therapy. Methods Between January 2003 and December 2018, 111 consecutive patients diagnosed with NGGCTs reviewed. Those who progressed after first line therapy were included in this study. Data of first line treatment, salvage treatment, clinicopathological features and survival were collected and analyzed. Results Totally, thirty patients (30/111, 27.0%) relapsed in our cohort, including 19 patients with accurate relapse information detail, and 11 patients who died of disease progression during follow up but without exact time and site of relapse. The median OS from diagnosis of the disease was 49.2 months (95% CI: 14.1 to 84.3 months) and 3-year OS was 54.3%. Patients who received both CSI and chemotherapy relapsed less than those who received reduced volume of radiotherapy or only CSI or only chemotherapy (22.5% vs. 45.5%, p=0.034). Of 19 patients who had detail information of recurrence time and site, the median time from diagnosis of disease to relapse was 9.5 months (2.2 to 72.1 months). Regarding to recurrence site, most patients relapsed in primary site (10/19, 52.6%) or distant intracranial (6/19, 31.6%). The recurrence site of other 3 patients were spinal (n=1), ventricular (n=1) and peritoneal (n=1). Conclusion Protracted follow-up is recommended because late recurrence is not uncommon. Primary tumor site and distant intracranial are the most prevalent relapsed location. Patients who relapsed could benefited from both CSI and salvage chemotherapy.

scholarly journals RARE-56. RECURRENCE PATTERN AND SURVIVAL FOR RELAPSED INTRACRANIAL NON-GERMINOMATOUS GERM CELL TUMORS: A SINGLE-INSTITUTION EXPERIENCE

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi233-vi233
Author(s):  
Lei Wen ◽  
Zhaoming Zhou ◽  
Juan Li ◽  
Cheng Zhou ◽  
Mingyao Lai ◽  
...  
Keyword(s):  
Overall Survival ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Salvage Chemotherapy ◽  
Primary Site ◽  
First Line ◽  
Primary Tumor Site ◽  
First Line Therapy ◽  
Line Therapy

Abstract PURPOSE Intracranial non-germinomatous germ cell tumors (NGGCTs) have lower overall survival than germinoma because higher recurrence usually occurs after first line therapy in NGGCTs. METHODS Between January 2003 and December 2017, 23 patients with clinically or pathologically diagnosed recurrent NGGCTs after first line therapy were reviewed at our institution. Data of first line treatment, salvage treatment, clinicopathological features and survival were collected and analyzed. RESULTS First line therapy including craniospinal irradiation (CSI) in 15 patients, surgery in 3 patients, Gamma knife in 2 patients, chemotherapy in 2 patients and whole brain radiotherapy (WBRT) in 1 patient. The median time to recurrence was 13.8 months (5.8 to 89.2). With reference to the distribution of relapsed lesions, there were 8 patients within the primary site, 6 with distant intracranially, 1 ventricularly, 5 in spinal cords, 1 with dual sites in both primary site and intracranially, and 1 patient evidenced only serologically positive. Three patients did not receive further treatment and was lost during follow-up. Of the other patients, 16 patients received salvage chemotherapy with or without surgery, 4 received CSI or radiosurgery. After median follow up of 54 months, 7 patients died of disease progression. The 4-year overall survival rate after recurrence was 55.4%. CONCLUSION Protracted follow-up is recommended because late recurrence is not uncommon. Primary tumor site and distant intracranial are the most prevalent relapsed location. Patients who relapsed could benefited from salvage chemotherapy.

scholarly journals TREATMENT RESULTS OF VIP (ETOPOSIDE, IFOSFAMIDE AND CISPLATIN) CHEMOTHERAPY AS A FIRST-LINE THERAPY IN METASTATIC GERM CELL TUMORS

2000 ◽  
Vol 91 (2) ◽  
pp. 55-61
Author(s):  
Tetsuya Yoshida ◽  
Junji Yonese ◽  
Tetsurou Tsukamoto ◽  
Sin-ichi Kitsukawa ◽  
Taisei Kin ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
First Line ◽  
Treatment Results ◽  
First Line Therapy ◽  
Line Therapy

scholarly journals Treatment and outcomes of UK and German patients with relapsed intracranial germ cell tumors following uniform first-line therapy

2017 ◽  
Vol 141 (3) ◽  
pp. 621-635 ◽  
Author(s):  
Matthew J. Murray ◽  
Shivani Bailey ◽  
Katja Heinemann ◽  
Jillian Mann ◽  
Ulrich K Göbel ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Intracranial Germ Cell Tumors

scholarly journals Pediatric and Adolescent Extracranial Germ Cell Tumors: The Road to Collaboration

2015 ◽  
Vol 33 (27) ◽  
pp. 3018-3028 ◽  
Author(s):  
Thomas A. Olson ◽  
Matthew J. Murray ◽  
Carlos Rodriguez-Galindo ◽  
James C. Nicholson ◽  
Deborah F. Billmire ◽  
...  
Keyword(s):  
Germ Cell ◽  
Primary Tumor ◽  
Germ Cell Tumors ◽  
Tumor Site ◽  
Primary Tumor Site ◽  
Heterogeneous Distribution ◽  
Long Term Treatment ◽  
Staging Systems ◽  
Pediatric Cancer Patients

During the past 35 years, survival rates for children with extracranial malignant germ cell tumors (GCTs) have increased significantly. Success has been achieved primarily through the application of platinum-based chemotherapy regimens; however, clinical challenges in GCTs remain. Excellent outcomes are not distributed uniformly across the heterogeneous distribution of age, histologic features, and primary tumor site. Despite good outcomes overall, the likelihood of a cure for certain sites and histologic conditions is less than 50%. In addition, there are considerable long-term treatment-related effects for survivors. Even modest cisplatin dosing can cause significant long-term morbidities. A particular challenge in designing new therapies for GCT is that a variety of specialists use different risk stratifications, staging systems, and treatment approaches for three distinct age groups (childhood, adolescence, and young adulthood). Traditionally, pediatric cancer patients younger than 15 years have been treated by pediatric oncologists in collaboration with their surgical specialty colleagues. Adolescents and young adults with GCTs often are treated by medical oncologists, urologists, or gynecologic oncologists. The therapeutic dilemma for all is how to best define disease risk so that therapy and toxicity can be appropriately reduced for some patients and intensified for others. Further clinical and biologic insights can only be achieved through collaborations that do not set limitations by age, sex, and primary tumor site. Therefore, international collaborations, spanning different cooperative groups and disciplines, have been developed to address these challenges.

Dose Escalation of Azacitidine in Patients Failing Standard or Investigational Combinations of the Agent in the Myelodysplastiic Syndrome or Evolved AML

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4932-4932
Author(s):  
Lewis R. Silverman ◽  
Shyamala C. Navada ◽  
Rosalie Odchimar-Reissig ◽  
Maria Michalak ◽  
Erin P Demakos ◽  
...  
Keyword(s):  
Median Survival ◽  
Standard Dose ◽  
Single Agent ◽  
Hematologic Toxicity ◽  
Cell Transplant ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Wide Range ◽  
Higher Doses

Abstract Abstract 4932 Background: The hypomethylating agent azacitidine (azaC) which can reverse epigenetic silencing, is the first agent demonstrated to alter the natural history of MDS and improve survival in higher-risk patients (Silverman JCO 2002, Fenaux Lancet Oncology 2009). AzaC also produces comparable rates of response in patients with non-proliferative AML and appears to affect survival (Silverman JCO 2006). The response rate to single agent azaC is about 50% with median duration of response about 14 to 22 months. Patients who are refractory to or relapse following first line therapy with azaC have a median survival of 4 to 6 months (Jabbour 2010, Prebet 2011). Options for these patients failing first-line therapy with azaC are limited and there is no standard of care. Investigational therapies are being explored but not always widely available for these patients. Prior studies with azaC explored higher doses but were inconclusive to a dose response effect secondary to the slow time to response with a median of 2 to 3 cycles. In vitro, azaC has a wide range of concentrations that can induce differentiation up to 4 μm. In patients the standard clinical dose achieves a plasma level of 1. 25 μm thus suggesting that higher doses might have a clinical benefit (Marcucci 2005). Methods: Patients who were refractory to or relapsing following treatment with an azaC based regimen for MDS where alternative investigational options were not available and who were not rapidly progressing (i. e rapidly rising WBC or myeloblast %), were treated with higher doses of single agent azaC. The dose was increased by 33% from the baseline prior failing regimen (eg 55 to 75 or 75 to 100 mg/m2). The azaC was administered SC × 7 days q 28 days; response status was assessed after 2 cycles. Patients stable or responding were continued on 28 day cycles. Myeloid cytokine support was utilized for patients with ANC < 200 and ESA support for patients who were RBC dependent. Results: As of the data cut for this submission 13 patients are evaluable for toxicity and response. Among the 13 patients the median age was 68 and 11 were male. All had been treated with azaC based regimens before and 10 had responded: 4 CR; 1 PR; 5 HI; 2 NR; 1 unknown. The immediate therapy prior to increased dosing included: azaC + histone deacetylase inhibitor (HDACi) (6); single agent azaC (5); investigational treatment (2). 6 had MDS (int-1 (2); int-2 (3); high (1) and 7 AML (all transformed following MDS all smoldering). Responses among evaluable patients have occurred in 11 of 13 (85%); 1 PR, 7 HI (4 CRm), 1 CRm, (CR+CRi=53%) 2 PRm, 1 SD, 1 NR. Although responses occurred, the abnormal MDS/AML clone persisted, suggesting that the higher dose did not have a cytotoxic effect on the malignant clone. A total of 117 cycles have been administered, range 2 to 17 with a mean 8 cycles. Median time to treatment failure was 11. 6 months and median survival is 17. 5 months. Eight patients have come off treatment for progression (5); relapse (2); co-morbidities (1). No grade 3 or 4 non-hematologic toxicities were observed. Hematologic toxicity was similar to that seen with standard dose azaC. Conclusion: Modification of the dose of azaC in select patients, who lack alternative options including investigational agents or stem cell transplant, may improve blood counts and reduce the bone marrow blasts. The quality of the response to the increased dose after primary failure does not attain the level of the original response in most, however, this approach may increase therapeutic options in a poor risk population. Investigations into the potential mechanisms of action are being explored. Disclosures: Silverman: celgene: Speakers Bureau. Demakos:celgene: Speakers Bureau.

The outcome of vincristine, dactinomycin D, ifosfamide and doxorubicin (VAIA) as first-line therapy for adult-patients with metastatic ewing sarcoma; a single-center experience.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e23501-e23501 ◽  
Author(s):  
Jean Paul Atallah ◽  
Mahmoud Abdelsatar Elshenawy ◽  
Ahmed ali Badran ◽  
Maaz Kamal Alata ◽  
Ahmed Gad ◽  
...  
Keyword(s):  
Overall Survival ◽  
Ewing Sarcoma ◽  
Primary Tumor ◽  
Univariate Analysis ◽  
Objective Response ◽  
Adult Patients ◽  
Categorical Variables ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

e23501 Background: Ewing sarcoma family of tumors (ESFT) is a rare malignancy among adults. Most studies from western countries have reported improvement in outcomes following multi-agent chemotherapy. We report our experience in the management of this disease among Arab ethnicity. The aim of this study is to assess the outcome of VAIA combination as a first-line treatment in Adult-patients with metastatic Ewing sarcoma. Methods: Patients who were newly diagnosed as metastatic Ewing sarcoma between 03/1997 and 11/2016 at King Faisal Specialist Hospital and Research Center, who received VAIA as first-line therapy were eligible. The patient's characteristics were summarized using Medians with interquartile ranges (IQR) and frequencies for continuous and categorical variables, respectively. Variables including age, sex, primary tumor size, site (skeletal vs extraskeletal) and extent of metastasis in correlation with progression and overall survival were analyzed using the Kaplan–Meier method and Cox proportional hazards regression. Results: Thirty-nine patients were identified. Male (26, 66.7%), Female (13, 33.3%). Skeletal (27, 69.2%), Extraskeletal (12, 30.8%). The median longest diameter of the primary tumor 9.75 (IQR 8-15). The most common metastatic sites were Lungs (22, 56.4%) & Bone (10, 25.6%), however, the least common sites were Bone Marrow (3, 7.7%) and liver (2, 5.1%). The median number of VAIA cycles was 10 cycles (IQR 5-14). Objective response rate (ORR) was noticed in 20 patients (51.2%) (Complete Remission (7, 17.9%), Partial Remission (13, 33.3%). One patient had stable disease and 12 (30.8%) patients had progressive disease. The assessment was not feasible in 3 (7.7%) patients. With a median follow up duration of 18 months (1-44).20 patients died (62.5%). The median PFS and OS was 10,18 months respectively with 3,5 years overall survival rate of;35.7%,26.9% respectively. Univariate analysis correlation among different variables were insignificant. Conclusions: VAIA chemotherapy combination showed poor outcomes among our patients in comparison to literature further improvement is needed in this aggressive malignancy in our region.

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