Salvage Chemotherapy for Patients With Advanced Pure Seminoma

2002 ◽  
Vol 20 (1) ◽  
pp. 297-301 ◽  
Author(s):  
Jacqueline Vuky ◽  
Satish K. Tickoo ◽  
Joel Sheinfeld ◽  
Jennifer Bacik ◽  
Alison Amsterdam ◽  
...  

PURPOSE: We describe the response to conventional or high-dose salvage chemotherapy in patients with advanced seminoma who experience disease progression after receiving first-line platinum-based treatment. PATIENTS AND METHODS: Twenty-seven patients with progressive, advanced, pure seminoma were treated with salvage chemotherapy. Fifteen patients were treated with conventional-dose cisplatin-and-ifosfamide combination chemotherapy. Twelve patients were treated with high-dose chemotherapy followed by autologous stem-cell rescue. RESULTS: Fifteen patients (56%) achieved a complete response (CR), nine achieved CR with a conventional-dose cisplatin and ifosfamide program, and six experienced CR after high-dose chemotherapy. Fourteen patients (52%) are alive and disease-free, with 13 (48%) continuously disease-free at a median follow-up of 72 months. Twelve (57%) of 21 patients whose pretreatment tumors were studied morphologically were found to have seminoma with atypia. Eight patients underwent resection after salvage chemotherapy; six with histologic findings of necrotic debris/fibrosis alone are alive and disease-free at last follow-up. Both patients with viable seminoma found at surgery died of disease. CONCLUSION: Most patients with advanced seminoma are cured with standard first-line programs of cisplatin and etoposide with or without bleomycin. A small minority of patients with pure seminoma have resistant tumors and require salvage chemotherapy. In this setting, approximately 50% of patients with recurrent pure seminoma achieve durable CR with conventional or high-dose salvage chemotherapy. Identification of biologic markers to predict clinical outcome and an enhanced understanding of the basic biologic features of seminoma may lead to improvements in the management of this disease.

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi159-vi160
Author(s):  
Kate Therkelsen ◽  
Christian Grommes

Abstract BACKGROUND Primary central nervous system lymphoma (PCNSL) is a rare central nervous system malignancy, and long-term follow up studies are uncommon. First line therapy is based on high-dose methotrexate and different consolidation therapy options. This is a long-term follow up study of PCNSL patients enrolled in a prospective trial using R-MPV chemotherapy regimen followed by high dose chemotherapy and autologous stem cell rescue to determine long-term survival and cognitive effects. METHODS From June 2005 to September 2011, 32 newly diagnosed immunocompentent PCNSL were enrolled. Patients received 5-7 doses of rituximab (500mg/m2), methotrexate (3.5 gm/m2), procarbazine (100mg/m2), and vincristine (1.4mg/m2) (R-MVP). Consolidation therapy consisted of high dose chemotherapy (HDC) with thiotepa (250 mg/m2), busulfan (3.2 mg/kg), and cyclophosphamide (60 mg/kg), followed by autologous stem cell rescue (ASCT) in those with partial or complete response to R-MVP. Long-term follow-up status including disease status, cognitive status (KPS, NANO score), and leukoencephalopathy (modified Fazkas Scale) were collected. RESULTS 26 of 36 underwent HDC and ACST. Of those, 3 died due to treatment related effects; 2 died of disease progression within two years after ASCT. After a median follow-up of 10.5 years, none of the remaining 21 patients progressed. At the time of last follow up, the median KPS was 90, compared to 80 at time of ASCT. The median NANO score and leukoencephalopathy score post ASCT and at follow-up did not change. Of note, 2 of 4 patients with a partial or complete response to R-MVP that elected not to proceed with HDC-ASCT consolidation, experienced progression at a mean of 52 months. CONCLUSION Long-term follow up demonstrates that treatment was tolerated well with stable leukoencephalopathy on MRI and good performance status. Disease recurrence 2 years after HDC with ASCT consolidation was not observed.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii394-iii395
Author(s):  
Christelle Dufour ◽  
Julien Masliah-Planchon ◽  
Marie-Bernadette Delisle ◽  
Anne Geoffray ◽  
Rachid Abbas ◽  
...  

Abstract PURPOSE To assess the 3-year EFS rate of children younger than 5 years of age with high-risk medulloblastoma (MB) treated according to the prospective multicenter trial HR MB-5. PATIENTS AND METHODS After surgery, all children received 2 cycles of Etoposide- Carboplatine. If partial (PR) or complete response (CR) was achieved after induction chemotherapy, children received 2 courses of thiotepa (600mg/m²) with stem cell rescue. For patients in CR after high-dose chemotherapy, they received one course of Cyclophosphamide – Busilvex with stem cell rescue (Phase I part). The others patients (not in PR after induction or in CR after thiotepa) were treated with 2 cycles of Temozolomide-Irinotecan followed by age-adapted craniospinal irradiation and maintenance treatment. RESULTS 28 children (2 to 4 years; median: 3.0 years) were enrolled. Group 3 MB were most common (57%). The response rate to Etoposide-Carboplatine was 60.7%. Among 20 patients treated with Thiotepa, 13 children were in CR and received Cyclophosphamide – Busilvex without radiotherapy. Out of them, 9 patients (45%) are alive in CR without craniospinal irradiation (median follow-up 5 years). Among 15 patients treated with radiotherapy, 8 patients are alive (median follow-up 3.8 years). The study was prematurely stopped for an excess of events. The median follow-up was 4 years (range 1.5 - 6.1). The 3-year EFS and OS were 42.3% [25.9 - 60.6] and 71.3% [52.7 - 84.7], respectively. CONCLUSIONS This risk-adapted strategy did not improve EFS in young children with high-risk MB. However, the study shows that good responders to chemotherapy can be cured without recourse to irradiation.


2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 336-336
Author(s):  
Michel S Beausoleil ◽  
Kylea R. Potvin ◽  
Kang Howson-Jan ◽  
D. Scott Ernst ◽  
Larry Stitt ◽  
...  

336 Background: Some men with mGCTs progressing after response to initial cisplatin-based combination chemotherapy are cured with CDCT as 1st salvage, however, many are not. Prognosis has recently been better defined by the IPFSG prognostic factors. HDCT with autologous stem cell rescue has been routinely offered after CR/PRm- remission with CDCT at our institution over the past two decades. We retrospectively reviewed our data to assess the validity of the IPFSG prognostic factors and evaluate the potential value of this approach. Methods: Eligible men with mGCTs progressing after at least 3 cycles of cisplatin-based chemotherapy received after 01 Jan 1990 and treated with cisplatin-based CDCT+/−HDCT (etoposide + carboplatin) were identified and data collected. Pts were classified into risk groups using IPFSG factors, PFS and OS were analyzed and results for CDCT+/−HDCT compared. Results: 38 eligible 1st salvage pts had received a median of 4 cycles (range, 1–7) of CDCT. 20 pts received CDCT alone & 18 pts received CDCT+HDCT. Overall median PFS was 24.6 months (95%CI, 7.3–28.7) and overall median OS was 34.6 months (95%CI, 17.2–51.3). Distribution by IPFSG category, 2-year PFS and 3-year OS rates within each risk category were very similar to IPFSG results. Two toxic deaths occurred with CDCT. Pts treated with CDCT+HDCT more often had better responses to 1st-line chemotherapy and pure seminoma histology. Overall pts treated with CDCT+HDCT had improved PFS (HR: 0.18; 95%CI, 0.07–0.51; p=0.001) and OS (HR: 0.25; 95%CI, 0.10–0.65; p=0.004) compared to CDCT alone. Examination by IPFSG risk category showed that the 2-year PFS and 3-year OS rates for CDCT+HDCT was higher in all prognostic groups except for the very high risk which did not have any HDCT pts. Conclusions: The IPFSG prognostic factors were valid in our 1st salvage mGCT pts. The safety of HDCT with etoposide and carboplatin was confirmed. HDCT was associated with improved PFS and OS outcomes, consistent with observations of Lorch et al (JCO 2011). Ideally the value of optimal CDCT+HDCT should be determined in comparison to optimal CDCT as first salvage therapy in men with metastatic GCT in a randomized trial.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2388-2388
Author(s):  
Paul Greaves ◽  
Andrew Wilson ◽  
Janet Matthews ◽  
Daniel L P Brown ◽  
Silvia Montoto ◽  
...  

Abstract Abstract 2388 High dose chemotherapy with autologous stem cell rescue (HDT-ASCR) currently offers patients with classical Hodgkin lymphoma (CHL) with primary refractory or relapsed disease the best chance of cure, particularly when offered in complete response (CR) following salvage therapy. Treatment of chemotherapy-refractory patients remains contentious and is associated with poor outcomes and high relapse rates. At St Bartholomew's Hospital, London (SBH), HDT-ASCR with BEAM (BCNU, etoposide, Ara-C and melphalan) has been administered only to patients who have demonstrated CR or partial response (PR) to salvage chemotherapy. We performed a retrospective intention to treat analysis on all patients for whom consolidation with BEAM as HDT-ASCR was planned between 1995 and 2008 to assess the success of this approach. Eligible patients with CHL were identified as those achieving less than CR to first-line chemotherapy (first-line failure), or those who had relapsed fewer than 5 years after first CR, were 18–60 years of age at the time of salvage therapy, and HIV negative. Initial chemotherapy comprised an anthracycline-containing regimen in all cases. 103 patients were identified (62% male, median age 31, range 18–59, median follow up 8 years, range 2–15 years). HDT-ASCR indications were first-line failure in 41 (39%) and first relapse in 62 (61%). Of the 41 patients in the first-line failure group, only 52% proceeded successfully to BEAM having demonstrated chemosensitivity: 75% following single-line salvage, [predominantly with ChlVPP (chlorambucil, vincristine, procarbazine and prednisolone) in 60% or gemcitabine-based chemotherapy in 20%], whereas 25% required two different lines of salvage chemotherapy. Of the 62 patients treated at first relapse, 82% proceeded successfully to BEAM, 95% following single-line salvage, predominantly with ChlVPP in 55%, VAPEC-B (vincristine, doxorubicin, prednisolone, etoposide, cyclophosphamide and bleomycin) in 20% and gemcitabine-based regimens in 10%. Only 5% required 2 or more lines of salvage (Figure 1). Overall survival (OS) at 5 years for all patients by intention to treat with HDT-ASCR was 63% (Figure 2); 76% for the relapse group, and 45% for the first line failure group. In the cohort who successfully received BEAM chemotherapy, OS was 75% at 5 years (with no significant survival difference between the relapsed and the first line failure groups) with a 100-day treatment-related mortality of 4%, the other deaths being from relapsed CHL except for one case of secondary malignancy occurring 15 years after BEAM. Salvage of CHL in relapse, or in those who have failed to achieve CR with first-line therapy remains an area in which improvements need to be made. There are few published analyses of outcome by intention to treat with HDT-ASCR. The relatively conservative strategy at SBH of offering HDT-ASCR only to those with chemosensitive disease at salvage has lead to excellent outcomes in the more selected population reaching HDT-ASCR, without compromising overall outcomes of the eligible population. Figure 1. Patient Pathways (n=103) Figure 1. Patient Pathways (n=103) Figure 2. Overall Survival Intention to treat with BEAM Figure 2. Overall Survival Intention to treat with BEAM Disclosures: Gribben: Roche: Consultancy; Celgene: Consultancy; GSK: Honoraria; Napp: Honoraria. Lister: Allos: Consultancy; Bioconnections: Consultancy; Astra Zeneca: Consultancy; Tenet: Consultancy; GSK: Chairman of Safety Monitoring Committee.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5082-5082
Author(s):  
J. Beyer ◽  
M. Hackenthal ◽  
A. Lorch ◽  
A. Neubauer ◽  
A. Dieing ◽  
...  

5082 Background: To determine the activity of high-dose chemotherapy (HDCT) as intensification of second salvage treatment (SST) in patients with multiple relapsed germ-cell tumors (GCT). Methods: Databases in Berlin and Marburg (Germany) on patients treated with HDCT between 1989 and 2008 for germ-cell tumors were screened. Among 534 patients overall, 71/534 (13%) patients were identified as scheduled for HDCT having failed at least one previous conventional-dose first-line and first-salvage chemotherapy regimen. Forty-nine patients who had received at least cisplatin- and etoposide as first-line as well as conventional-dose cisplatin as first-salvage treatment and were diagnosed after January 1, 1990, were further analyzed. Results: Median age at SST was 32 years (range 19 to 52 years). Median follow-up for surviving patients was 4 years (range 1,7 to 8,5 years). Histology was pure seminoma in 5/49 (10%) patients and non-seminoma or mixed histologies in 44/49 (90%). The median number of cisplatin-based treatment cycles prior to SST was 7 (range 5 to 11 cycles). Three of forty-nine (6%) patients either progressed or died prior to scheduled HDCT, the remaining 46/49 (94%) received either single or sequential HDCT. The rate of favorable responses to HDCT as intensification of SST was 27/49 (55%). Ten patients are alive without progression. One additional patient is lost-to-follow at four years without progression. The projected overall survival rate at five years after initiation of SST was 17%. Conclusions: HDCT can induce long term remissions even in patients with multiple relapsed GCT. No significant financial relationships to disclose.


2007 ◽  
Vol 25 (3) ◽  
pp. 247-256 ◽  
Author(s):  
Robert J. Motzer ◽  
Craig J. Nichols ◽  
Kim A. Margolin ◽  
Jennifer Bacik ◽  
Paul G. Richardson ◽  
...  

Purpose To investigate the role of high-dose chemotherapy (HDCT) as first-line treatment in patients with metastatic germ cell tumor (GCT) and poor-prognostic clinical features. Serum tumor marker decline during chemotherapy was assessed prospectively as a predictor of treatment outcome. Patients and Methods In this randomized phase III trial, previously untreated patients with intermediate- or poor-risk GCT received either four cycles of standard bleomycin, etoposide, and cisplatin (BEP alone), or two cycles of BEP followed by two cycles of HDCT containing carboplatin and then by hematopoietic stem-cell rescue (BEP + HDCT). Serum tumor markers alpha-fetoprotein and human chorionic gonadotrophin were correlated with treatment outcome as a secondary end point. Results Two hundred nineteen patients were randomly assigned: 108 to BEP + HDCT and 111 to BEP alone. The 1-year durable complete response rate was 52% after BEP + HDCT and 48% after BEP alone (P = .53). Patients with slow serum tumor marker decline (alpha-fetoprotein and/or human chorionic gonadotrophin) during the first two cycles of chemotherapy had a shorter progression-free survival and overall survival compared with patients with satisfactory marker decline (P = .02 and P = .03, respectively). Among 67 patients with unsatisfactory marker decline, the 1-year durable complete response proportion was 61% for patients who received HDCT versus 34% for patients receiving BEP alone (P = .03). Conclusion The routine inclusion of HDCT in first-line treatment for GCT patients with metastases and a poor predicted outcome to chemotherapy did not improve treatment outcome. Frequent serum marker determinations to estimate marker decline during the first two cycles of BEP chemotherapy provide a clinically useful estimate of outcome.


KYAMC Journal ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 124-128
Author(s):  
Zulfia Zinat Chowdhury ◽  
Mohammad Ali ◽  
AKM Mynul Islam ◽  
Salina Haque ◽  
Tamanna Bahar ◽  
...  

Background: Multiple Myeloma (MM) represents approximately 15% of all hematological malignancies. Despite the use of high-dose chemotherapy followed by stem cell rescue MM remains incurable at present. The goal is to control the disease as much as possible, providing the best quality of life to patients for the longest duration. Currently, CTDa (attenuated Cyclophosphamide, Thalidomide, Dexamethasone) is the best option of treatment as it is cost-effective, with no need for hospitalization with a good response. Objective: To find out the symptomatic responses and toxicities of CTDa in Multiple Myeloma patients. Materials and Methods: 25 patients of newly diagnosed MM patients were treated in the Haematology Department, Bangabandhu Sheikh Mujib Medical University (BSMMU) from July 2016 to July 2017. The mean age of the patients was 54 years, Male female ratio was 1.5:1 and most of the patients were farmers. After induction of 4 to 6 cycles of CTDa all patients were followed up at 6th and 12th weeks. At follow up we evaluated improvement of weakness, bone pain, Hb%, ESR, monoclonal protein, ß2microglobulin, bone marrow plasma cells and serum calcium and albumin level. Adverse effects, such as peripheral neuropathy, thromboembolic events, hyperglycemia, constipation, rash, and somnolence were also assessed. Results: Among 25 patients, complete response achieved only 13 patients (52%), where 20% and 16% of patients belonged to partial or no response respectively. The death occurred in 2 cases (12%). Conclusion: CTDa is a gentle approach to treat an especially frail group of patients, since virtually all patients ultimately relapse. KYAMC Journal Vol. 11, No.-3, October 2020, Page 124-128


1995 ◽  
Vol 13 (5) ◽  
pp. 1089-1095 ◽  
Author(s):  
W P Vaughan ◽  
E Kris ◽  
J Vose ◽  
P J Bierman ◽  
P Gwilt ◽  
...  

PURPOSE A phase I/II study was performed to evaluate the incorporation of hydroxyurea (HU) into high-dose chemotherapy of non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS Thirty-eight patients with primary refractory and refractory relapsed NHL were treated with carmustine (BCNU) (300 mg/m2 on day -8), cyclophosphamide (Cy) (2.5 g/m2/d on days -8 and -7), etoposide (E) (150 mg/m2 every 12 hours on days -6, -5, and -4), and HU (BCHE) with autologous hematopoietic stem-cell rescue. Twenty-one patients received HU in a dose escalation of 2 to 12 g/m2 intravenously (IV) by 72-hour continuous infusion. When the IV formulation was not available, 17 patients were given 18 g/m2 of HU orally in divided doses every 6 hours over the same 72-hour period. RESULTS The dose-limiting toxicity of 72-hour continuous infusion HU in this regimen was mucositis. Endotracheal intubation was necessary to protect the airway in two thirds of patients treated at 12 g/m2. Six patients (oral BCHE, five of 17; IV BCHE, one of 21) died with nonresponding or progressive disease and, at least in part, from the complications of the high-dose chemotherapy. Seventeen patients (45%) achieved complete remission (CR). More patients treated with IV BCHE achieved CR than patients treated with oral BCHE (12 of 21 v five of 17; P < .1, chi 2 test). Nine patients (two of 17 oral BCHE and seven of 21 IV BCHE) remain disease-free as of January 31, 1994, with a minimum follow-up time of 3 years. The lower mortality and higher response rate with IV BCHE translated into a significantly superior probability of progression-free survival (PFS) (33% at 4 year v 12% for oral BCHE; P = .048, log-rank test). CONCLUSION High-dose BCHE is effective treatment for primary refractory and refractory relapsed NHL. Continuous IV HU appears to be less toxic and more effective than intermittent oral HU in this regimen.


2018 ◽  
Vol 104 (6) ◽  
pp. 471-475 ◽  
Author(s):  
Mouhammed Kelta ◽  
Jamal Zekri ◽  
Ehab Abdelghany ◽  
Jalil Ur Rehman ◽  
Zahid Amin Khan ◽  
...  

Purpose: High-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) is used to treat patients with relapsed Hodgkin’s lymphoma. In this retrospective study we report our experience with patients who underwent HDCT and ASCT. Methods: All patients ≥15 years old with relapsed/refractory Hodgkin’s lymphoma who underwent HDCT and ASCT between June 2001 and December 2013 were included. Results: Fifty-four patients were identified. Median age at transplant was 22 years (range 15-49 years); 26 were men and 28 were women. Forty-eight patients (89%) underwent HDCT and ASCT after achieving a radiological response to salvage chemotherapy. The rate of radiological complete response to salvage chemotherapy was 13% and reached 50% within 3 months of ASCT in assessable patients. After a median follow-up of 25 months, 31 patients (57%) were still alive with no evidence of relapse or progression. Median event-free survival (EFS) was 24 months (95% CI 8.7-39.3) and 3-year EFS was 56%. Median overall survival (OS) was not reached and 3-year OS was 82.5%. Bulky mediastinal disease at relapse, hemoglobin level, and number of salvage regimens did not significantly impact EFS in univariate and multivariate analyses. After transplantation there was a trend towards longer EFS (30 vs. 24 months; p = 0.36) in patients with a longer time from the end of first-line treatment until relapse (≥12 vs. <12 months). The 100-day transplant-related mortality was 5.5%. Conclusions: HDCT and ASCT for relapsed/refractory Hodgkin’s lymphoma is safe. Our findings are consistent with published phase III results. Longer follow-up is warranted.


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