scholarly journals Optimized first-line therapy for stage IV breast cancer brings long-term disease-free survival: a case report and biological analysis

2020 ◽  
Vol 1 ◽  
pp. 7-7
Author(s):  
Li Bian ◽  
Fengrui Xu ◽  
Tao Wang ◽  
Huiqiang Zhang ◽  
Yang Cao ◽  
...  
2014 ◽  
Vol 32 (30_suppl) ◽  
pp. 209-209
Author(s):  
Sky Breeden Vanderburg ◽  
A. Lindsay Frazier ◽  
Jane Kim

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.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2431-2431 ◽  
Author(s):  
Silvia Rivas-Vera ◽  
Enrique Baez ◽  
Pedro Sobrevilla-Calvo ◽  
Severiano Baltazar ◽  
Francisco Tripp ◽  
...  

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.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 591-591 ◽  
Author(s):  
Tong Wu ◽  
Jie Zhao ◽  
Bin Jiang ◽  
Shu-Lan Wu ◽  
Ping-Di Yang ◽  
...  

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.


2019 ◽  
Vol 37 (2) ◽  
pp. 105-114 ◽  
Author(s):  
Thomas Ruhstaller ◽  
Anita Giobbie-Hurder ◽  
Marco Colleoni ◽  
Maj-Britt Jensen ◽  
Bent Ejlertsen ◽  
...  

Purpose Luminal breast cancer has a long natural history, with recurrences continuing beyond 10 years after diagnosis. We analyzed long-term follow-up (LTFU) of efficacy outcomes and adverse events in the Breast International Group (BIG) 1-98 study reported after a median follow-up of 12.6 years. Patients and Methods BIG 1-98 is a four-arm, phase III, double-blind, randomized trial comparing adjuvant letrozole versus tamoxifen (either treatment received for 5 years) and their sequences (2 years of one treatment plus 3 years of the other) for postmenopausal women with endocrine-responsive early breast cancer. When pharmaceutical company sponsorship ended at 8.4 years of median follow-up, academic partners initiated an observational, LTFU extension collecting annual data on survival, disease status, and adverse events. Information from Denmark was from the Danish Breast Cancer Cooperative Group Registry. Intention-to-treat analyses are reported. Results Of 8,010 enrolled patients, 4,433 were alive and not withdrawn at an LTFU participating center, and 3,833 (86%) had at least one LTFU report. For the monotherapy comparison of letrozole versus tamoxifen, we found a 9% relative reduction in the hazard of a disease-free survival event with letrozole (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.01). HRs for other efficacy end points were similar to those for disease-free survival. Efficacy of letrozole versus tamoxifen for contralateral breast cancer varied significantly over time (0- to 5-, 5- to 10-, and > 10-year HRs, 0.62, 0.47, and 1.35, respectively; treatment-by-time interaction P = .005), perhaps reflecting a longer carryover effect of tamoxifen. Reporting of specific long-term adverse events seemed more effective with national registry than with case-record reporting of clinical follow-up. Conclusion Efficacy end points continued to show trends favoring letrozole. Letrozole reduced contralateral breast cancer frequency in the first 10 years, but this reversed beyond 10 years. This study illustrates the value of extended follow-up in trials of luminal breast cancer.


2017 ◽  
Vol 19 (1) ◽  
Author(s):  
Jan Poleszczuk ◽  
Kimberly Luddy ◽  
Lu Chen ◽  
Jae K. Lee ◽  
Louis B. Harrison ◽  
...  

1999 ◽  
Vol 17 (4) ◽  
pp. 1118-1118 ◽  
Author(s):  
C. Hudis ◽  
M. Fornier ◽  
L. Riccio ◽  
D. Lebwohl ◽  
J. Crown ◽  
...  

PURPOSE: We conducted a phase II pilot study of dose-intensive adjuvant chemotherapy with doxorubicin followed sequentially by high-dose cyclophosphamide to determine the safety and feasibility of this dose-dense treatment and to estimate the disease-free and overall survival in breast cancer patients with four or more involved axillary lymph nodes. PATIENTS AND METHODS: Seventy-three patients received adjuvant treatment with four cycles of doxorubicin 75 mg/m2 as an intravenous bolus every 21 days, followed by three cycles of cyclophosphamide 3,000 mg/m2 every 14 days with granulocyte colony-stimulating factor support. RESULTS: Seventy-one patients were assessable, and all but two completed all planned chemotherapy. There was no treatment-related mortality. The most common toxicity was neutropenic fever, which occurred in 39% of patients. Median disease-free survival is 66 months (95% confidence interval, 34 to 98 months), and median overall survival has not yet been reached. At 5 years of follow-up, the disease-free survival is 51.7%, and overall survival is 60.0%. There is no long-term treatment-related toxicity, and no cases of acute myelogenous leukemia or myelodysplastic syndrome have been observed. CONCLUSION: Our pilot study of doxorubicin followed by cyclophosphamide demonstrates the safety and feasibility of the sequential dose-dense plan. Long-term follow-up, although noncomparative, is promising. However, this regimen is associated with a higher incidence of toxicity (and also higher costs) than the standard dose and schedule of doxorubicin and cyclophosphamide, and therefore it should not be used as conventional therapy in the absence of demonstrated improvement of outcome. Randomized trials testing the dose-dense approach have been completed but not yet reported. Because the sequential plan can decrease overlapping toxicities, it is an appropriate platform for the addition of newer active agents, such as taxanes or monoclonal antibodies.


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