Determining optimal first-line chemotherapy for good and intermediate prognosis testicular germ cell tumors using decision analysis.

2014 ◽  
Vol 32 (30_suppl) ◽  
pp. 209-209
Author(s):  
Sky Breeden Vanderburg ◽  
A. Lindsay Frazier ◽  
Jane Kim
Keyword(s):  
Life Expectancy ◽  
Germ Cell Tumors ◽  
Disease Free Survival ◽  
First Line ◽  
Testicular Germ Cell ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy ◽  
Disease Free

209 Background: Since 80-90% of testicular germ cell tumors (GCTs) are cured after first line therapy alone, minimizing toxicity should be an important consideration in the initial treatment decision between cisplatin and carboplatin. Cisplatin has been shown to be superior in 5-year disease-free survival, but cisplatin use confers a higher risk of key long-term toxicities. This study aims to quantify this trade-off between disease-free survival and toxicities using decision analysis. Methods: We developed a mathematical decision-analytic model that simulates competing strategies of initial treatment with cisplatin or carboplatin in terms of treatment response, long-term toxicity, and mortality associated with first, second, and third line therapies for patients with good and intermediate prognosis testicular GCTs and a median age of 20 years at diagnosis. Treatment toxicities included ototoxicity, neurotoxicity, and nephrotoxicity. Monthly probabilities were weighted means derived from a systematic review of total follow-up data reported in seminal clinical trials. The model projected life expectancies for each strategy. Sensitivity analysis was conducted to examine the impact of uncertain inputs and assumptions. Results: The life expectancies at diagnosis for cisplatin and carboplatin strategies were 436.1 months (36.3 years) and 663.2 months (55.3 years) respectively. Sensitivity analyses revealed life expectancy figures largely dependent on the risk of nephrotoxicity occurrence from first line therapy and death from nephrotoxicity. Unless these base monthly probabilities were reduced by 87% and 99% respectively, carboplatin consistently yielded higher life expectancy than cisplatin. Conclusions: Under the current model, first line carboplatin therapy yields longer life expectancy than cisplatin, but this difference is highly sensitive to variables concerning nephrotoxicity. These preliminary results suggest that first line carboplatin therapy could yield higher life expectancy, though this result may be mediated by inclusion of other factors in future analyses, including updated estimates of mortality from nephrotoxicity or other toxicities.

Is First Line Single Agent Rituximab the Best Treatment for Indolent Non-Hodgkin’s Lymphoma? Update of a Multicentric Study Comparing Rituximab vs CNOP vs Rituximab Plus CNOP.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2431-2431 ◽  
Author(s):  
Silvia Rivas-Vera ◽  
Enrique Baez ◽  
Pedro Sobrevilla-Calvo ◽  
Severiano Baltazar ◽  
Francisco Tripp ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Single Agent ◽  
Disease Free Survival ◽  
First Line ◽  
Free Survival ◽  
Overall Response ◽  
First Line Therapy ◽  
Line Therapy ◽  
Disease Free

Abstract Purpose: To evaluate efficacy, safety, Disease-Free Survival (DFS) and Overall Survival (OS) in patients with indolent non-Hodgkin’s lymphoma (NHL) treated with chemotherapy vs. immunotherapy vs immunochemotherapy as first-line therapy, an up-date report. Methods: Patients with indolent NHL were randomized to receive: (A) Rituximab x 6/w, (B) CNOP (cyclophosphamide, mitoxantrone, vincristine and prednisone) x 6 or (C) R-CNOP x 6, at standard doses. Results: 195 patients were included, 183 are evaluable for OS and toxicity (A:62, B:55 and C:66), 144 are evaluable for overall response rate (ORR) and DFS (A:53, B:41 and C:50). Clinical characteristics: 89 male (45.6%), mean age 59±14 (±SD), 148 (75.9%) in stage (III/IV), without significant differences between groups. Overall Response Rate (CR+PR) was: A: 84.9%, B:83.4% and C:90% (P=0.545). Neutropenia grade 3/4 was more frequent in the chemotherapy groups: A: 4.8%, B: 23.6% and C:18.2% (P=0.001) as it was the infectious toxicity (grade 2/4): A:4.8%, B:5.5% and C:15.2% (P=0.07). DFS at 24 months was: A 68%, B:65% and C:70%, (P=0.93) and the OS was A:87%, B:84% and C:78%. P=0.89. Conclusions: We did not find any important differences, between groups, regarding the Overall Response Rate, Disease Free Survival and Overall Survival at 24 months. However, single agent rituximab was better tolerated, with less toxicity in comparison with the chemotherapy containing groups. Based on these findings, it maybe reasonable to use immunotherapy only, as first-line therapy for patients with indolent NHL.

Tetra-Arsenic Tetra-Sulfide Containing Triple-Agent Regimen as the First Line Therapy for Acute Promyelocytic Leukemia: Expeditiously Consecutive Complete Remission and Improved Disease-Free Survival.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 591-591 ◽  
Author(s):  
Tong Wu ◽  
Jie Zhao ◽  
Bin Jiang ◽  
Shu-Lan Wu ◽  
Ping-Di Yang ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Cytotoxic Agents ◽  
Newly Diagnosed ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy ◽  
Disease Free ◽  
Retinoid Acid ◽  
Hematological Remission

Abstract Our previous study has demonstrated that tetra-arsenic tetra-sulfide (As4S4) treatment alone is highly effective and safe in both induction and maintenance therapy in acute promyelocytic leukemia (APL) patients (Lu DP et al, Blood2002; 99: 3136). In current clinical study, we explored whether As4S4 combined sequentially or simultaneously with all-trans retinoid acid (ATRA) and cytotoxic agents according to specific clinical condition as the first line therapy could expedite complete remission (CR) but in a safer way and further improve disease-free survival (DFS). The treatment-related toxicities were also studied. From April 2001 to May 2007, 114 patients with APL in a median age of 32.5 years (10–73 years) were enrolled including consecutive 68 newly diagnosed cases and 46 patients in hematological remission. For induction therapy, both As4S4 (60 mg/kg) and, if leukocytosis or retinoid acid syndrome was not a risk, ATRA (25mg/m2) were taken orally per day till CR. Cytotoxic agents such as mitoxantrone and/or hydroxyurea were added when WBC counts were more than 4 × 109/L. After hematological remission, 4 to 6 cycles of combined chemotherapy were given, and followed by alternatively oral use of As4S4 (3 cycles) and ATRA (1 cycle) in outpatient base for maintenance therapy until 4 years after diagnosis. PML/RARa transcript was monitored quantitatively by real-time PCR. Arsenic levels in blood and urine were also monitored with an atomic absorption spectrophotometer. Consecutive 68 newly diagnosed patients all achieved complete hematological remission in a median time of 29.5 days (14 – 62 days) without early death. The median time to achieve molecular remission was 61.5 days (34 – 120 days). Four out of 114 patients relapsed. One of them had obtained CR again. One patient died from leukemia relapse. Treatment with As4S4containing regimen was well tolerated. Mild gastrointestinal discomfort, transient elevation in liver enzyme, rash, and edema were noted in a few cases. Estimated DFS rate for 4 years was 94%, with a median follow-up time of 36.5 months (3–76 months). Our encouraging results show that faster consecutive CR, higher DFS rate and better quality of life have been achieved with the above regimen as the first line therapy for APL patients.

scholarly journals Cost-Effectiveness of Pembrolizumab Plus Chemotherapy Versus Pembrolizumab Monotherapy in Metastatic Non-Squamous and Squamous NSCLC Patients With PD-L1 Expression ≥ 50%

2022 ◽  
Vol 12 ◽  
Author(s):  
Qiao Liu ◽  
Zhen Zhou ◽  
Xia Luo ◽  
Lidan Yi ◽  
Liubao Peng ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Life Expectancy ◽  
Cost Effective ◽  
Base Case ◽  
First Line ◽  
Term Survival ◽  
First Line Therapy ◽  
Line Therapy ◽  
Nsclc Patients

Objective To compare the cost-effectiveness of the combination of pembrolizumab and chemotherapy (Pembro+Chemo) versus pembrolizumab monotherapy (Pembro) as the first-line treatment for metastatic non-squamous and squamous non-small-cell lung cancer (NSCLC) with PD-L1expression ≥50%, respectively, from a US health care perspective.Material and Methods A comprehensive Makrov model were designed to compare the health costs and outcomes associated with first-line Pembro+Chemo and first-line Pembro over a 20-years time horizon. Health states consisted of three main states: progression-free survival (PFS), progressive disease (PD) and death, among which the PFS health state was divided into two substates: PFS while receiving first-line therapy and PFS with discontinued first-line therapy. Two scenario analyses were performed to explore satisfactory long-term survival modeling.Results In base case analysis, for non-squamous NSCLC patients, Pembro+Chemo was associated with a significantly longer life expectancy [3.24 vs 2.16 quality-adjusted life-years (QALYs)] and a substantially greater healthcare cost ($341,237 vs $159,055) compared with Pembro, resulting in an ICER of $169,335/QALY; for squamous NSCLC patients, Pembro+Chemo was associated with a slightly extended life expectancy of 0.22 QALYs and a marginal incremental cost of $3,449 compared with Pembro, resulting in an ICER of $15,613/QALY. Our results were particularly sensitive to parameters that determine QALYs. The first scenario analysis yielded lower ICERs than our base case results. The second scenario analysis founded Pembro+Chemo was dominated by Pembro.Conclusion For metastatic non-squamous NSCLC patients with PD-L1 expression ≥50%, first-line Pembro+Chemo was not cost-effective when compared with first-line Pembro. In contrast, for the squamous NSCLC patient population, our results supported the first-line Pembro+Chemo as a cost-effective treatment. Although there are multiple approaches that are used for extrapolating long-term survival, the optimal method has yet to be determined.

Vinblastine plus ifosfamide plus cisplatin as initial salvage therapy in recurrent germ cell tumor.

1998 ◽  
Vol 16 (7) ◽  
pp. 2500-2504 ◽  
Author(s):  
P J Loehrer ◽  
R Gonin ◽  
C R Nichols ◽  
T Weathers ◽  
L H Einhorn
Keyword(s):  
Germ Cell ◽  
Performance Status ◽  
Cell Cancer ◽  
Germ Cell Tumors ◽  
Disease Free Survival ◽  
Previous Treatment ◽  
Serum Markers ◽  
Free Survival ◽  
Disease Free

PURPOSE This study was designed to assess the effectiveness of vinblastine, ifosfamide, and cisplatin (VeIP) as second-line therapy in patients with recurrent germ cell tumors with previous treatment with cisplatin plus etoposide, usually in combination with bleomycin. PATIENTS AND METHODS From July 1984 through December 1989, 135 patients with progressive, disseminated germ cell tumors after cisplatin-etoposide-based combination therapy induction chemotherapy were treated with VeIP. Patients who progressed within 3 weeks of previous cisplatin therapy were not eligible. Progression was documented by biopsy or increasing serum markers. No exclusion was made on the basis of metastatic site or performance status. The dosages were vinblastine 0.11 mg/kg/d (days 1 and 2), ifosfamide 1.2 gm/m2/d (days 1 through 5), and cisplatin 20 mg/m2/d (days 1 through 5), with courses repeated every 21 days for four cycles. RESULTS Sixty-seven (49.6%) patients achieved a disease-free status after chemotherapy with or without surgical resection of residual carcinoma or teratoma. Overall, 42 (32%) patients are alive and 32 (23.7%) are continuously free of disease. None of the 32 patients with nonseminomatous extragonadal tumors are disease-free compared with 30 of 100 patients with gonadal primaries. Two of three extragonadal seminomas are continuously disease-free. CONCLUSION VeIP is capable of producing durable complete remissions in patients with disseminated germ cell cancer who relapse after cisplatin-etoposide-based induction therapy. Long-term disease-free survival is not seen in those patients with extragonadal nonseminomatous germ cell tumors.

Cisplatin-based combination chemotherapy for disseminated germ cell tumors: long-term follow-up.

1988 ◽  
Vol 6 (8) ◽  
pp. 1239-1247 ◽  
Author(s):  
B J Roth ◽  
A Greist ◽  
P S Kubilis ◽  
S D Williams ◽  
L H Einhorn
Keyword(s):  
Germ Cell ◽  
Functional Status ◽  
Combination Chemotherapy ◽  
Germ Cell Tumors ◽  
Disease Free Survival ◽  
Healthy Children ◽  
Free Survival ◽  
Disease Free

A retrospective analysis of the initial 229 cases of disseminated germ cell tumors treated at Indiana University with cisplatin, vinblastine, and bleomycin (PVB), with or without doxorubicin revealed 146 patients who are alive and disease-free with a minimum follow-up of 6 years and a median follow-up of 8.5 years. At 12 years, the estimated probability of survival is 65.0%, and the estimated probability of relapse-free survival for complete responders is 83.5%. Long-term complications, such as clinically significant organ toxicity or therapy-related second malignancies, have not been observed. The functional status of survivors is maintained, with 95% returning to their pretherapy status, of which 88% are fully employed. Of patients receiving chemotherapy without abdominal surgery, 35% have fathered healthy children posttherapy. Achievement of complete remission (CR) in disseminated germ cell tumors with cisplatin-based combination chemotherapy translates to long-term disease-free survival and cure for the majority of patients, with preservation of functional status.

Conditional survival of patients with metastatic testicular germ-cell tumors (MT-GCT) treated with first-line curative therapy.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 472-472
Author(s):  
Jenny J. Ko ◽  
Brandon David Bernard ◽  
Ben Tran ◽  
Haocheng Li ◽  
Tehmina Asif ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Germ Cell ◽  
Risk Group ◽  
Conditional Survival ◽  
First Line ◽  
Testicular Germ Cell ◽  
Curative Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Disease Free

472 Background: The IGCCCG risk stratification prognosticates survival outcomes in metastatic testicular germ cell tumour (MT-GCT), but how the initial risk changes over time for those who survived since curative treatment (conditional survival) is unknown. We evaluated conditional survival in patients with MT-GCT who were eligible for first-line therapy. Methods: We included patients who were eligible for first-line therapy for MT- GCT at 5 tertiary cancer centres from 1990 to 2012. We assessed 2-year (Y) conditional overall (COS) and disease-free survival (CDFS) at a given timepoint, defined as the probability of surviving, or surviving and disease-free, respectively, for an additional 2Y at a given timepoint since the start of first-line treatment. Outcomes were stratified by IGCCCG risk criteria, pathology and age. Results: For all patients (n = 942, favourable 63%/intermediate 19%/poor 16%), median follow-up was 99 months (m) (IQR 56-141); 2YCOS increased from 92% (95% CI 91%–94%) at baseline to 98% (95% CI 97%–99%) at 24m, and 2Y CDFS increased from 83% (95% CI: 81%-86%) at baseline to 98% (95% CI 97%-99%) at 24m after diagnosis. 2YCOS changed little in the IGCCCG favourable and intermediate groups, but in the poor-risk group, improved from 71% (95% CI 64%–78%) at 0m to 93% (95% CI 89%-98%) at 24m. 2Y CDFS for favourable risk group improved significantly at 12m (91% baseline vs. 95% at 18m); intermediate, at 12m (84% baseline vs. 95% at 12m); poor, at 12 m (55% baseline vs. 85% at 12m). Baseline IGCCCG risk stratification was not associated with long-term COS or CDFS for patients who survived to > 2Y post therapy. No significant differences in COS and CDFS were noted between seminoma and non-seminoma, while older patients ( > = 40) had inferior 2Y COS from 0-18m but no differences were noted after 18m. Conclusions: Our data suggest that the concept of conditional survival applies to patients with MT-GCT treated with curative therapy. A poor-risk patient, after 2Y of survival, had the same probability of relapse and survival as a favourable/intermediate risk patient.

Phase II Study of Paclitaxel Plus Gemcitabine in Refractory Germ Cell Tumors (E9897): A Trial of the Eastern Cooperative Oncology Group

2002 ◽  
Vol 20 (7) ◽  
pp. 1859-1863 ◽  
Author(s):  
Stuart Hinton ◽  
Paul Catalano ◽  
Lawrence H. Einhorn ◽  
Patrick J. Loehrer ◽  
Timothy Kuzel ◽  
...  
Keyword(s):  
Germ Cell ◽  
Phase Ii Study ◽  
Single Case ◽  
Eastern Cooperative Oncology Group ◽  
Germ Cell Tumors ◽  
Disease Free Survival ◽  
Great Success ◽  
Free Survival ◽  
Disease Free

PURPOSE: Despite great success in the treatment of disseminated germ cell tumors, 20% of patients are incurable and become candidates for investigational therapy. Paclitaxel and gemcitabine have shown activity as single agents in refractory germ cell tumors and can be combined with manageable toxicity. PATIENTS AND METHODS: Patients with germ cell tumors believed to be incurable with chemotherapy or surgery were treated with paclitaxel 110 mg/m2 and gemcitabine 1,000 mg/m2 intravenously on days 1, 8, and 15 of a 4-week cycle for a maximum of six cycles. Patients were evaluated for response and toxicity. RESULTS: Twenty-eight of 30 enrolled patients were assessable. Toxicity was primarily hematologic but was manageable with only a single case of neutropenic fever. Six (21.4%) of 28 patients responded, including three complete responses. Two of the complete responders were continuously disease-free at 15+ and 25+ months. CONCLUSION: Paclitaxel plus gemcitabine is an active regimen in refractory germ cell tumors, with an acceptable toxicity profile. This regimen has the possibility for long-term disease-free survival in this refractory patient population.

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