Comparison of standard versus high dose of paclitaxel with ifosfamide and cisplatin (TIP) in salvage therapy of germ cell tumors (GCTs).

e15028 Background: Currently, TIP with higher dose of paclitaxel (250mg/m2) is considered standard salvage chemotherapy in GCTs with good prognostic features. However, until 2007, we utilized regimen with standard dose of paclitaxel (175mg/m2). The aim of this study was to compare the efficacy of TIP with the standard versus higher dose of paclitaxel as first salvage therapy for patients with relapsed GCTs. Methods: This retrospective study included 64 patients with relapsed GCTs treated with TIP as first salvage therapy between 1998 and 2010 in two major cancer centers in Slovakia. Forty five patients (70%) patients had favorable prognostic features for response (testis primary tumor site and prior complete response to induction chemotherapy regimen). Four cycles of standard dose (175mg/m2, 37 patients) or higher dose (250 mg/m2, 27 patients) of paclitaxel (day 1) with ifosfamide 1.2 g/m2 (day 1-5) and cisplatin 20 mg/m2 (day 1-5) were given 21 days apart with G-CSF support, followed by resection of resectable radiographic residua. Results: Nineteen of 37 (51%) patients treated with standard dose of paclitaxel achieved favourable response (complete remission or partial remission with negative serum tumor markers) compared to 20 of 27 (74%) patients treated with higher dose of paclitaxel (p = 0.07). In median follow-up of 23.9 months 37 patients (58%) experienced disease relapse and 33 (52%) patients died. Patients treated with higher dose of paclitaxel had better progression-free survival (median: not reached vs. 7 months, HR = 0.54, 0.28 - 1.04; p = 0.06) and overall survival (median: not reached vs. 33 months, HR = 0.69, 0.34-1.39; p = 0.31) compared to patients treated with standard dose of paclitaxel. Conclusions: Our data support the hypothesis that higher dose of paclitaxel with ifosfamide and cisplatin is associated with better outcome compared to standard dose of paclitaxel in patients with relapsed GCTs treated in first relapse.

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Paclitaxel Plus Ifosfamide Followed by High-Dose Carboplatin Plus Etoposide in Previously Treated Germ Cell Tumors

Journal of Clinical Oncology ◽

10.1200/jco.2006.06.9401 ◽

2007 ◽

Vol 26 (1) ◽

pp. 85-90 ◽

Cited By ~ 90

Author(s):

G. Varuni Kondagunta ◽

Jennifer Bacik ◽

Joel Sheinfeld ◽

Dean Bajorin ◽

Manjit Bains ◽

...

Keyword(s):

Germ Cell ◽

Prospective Trial ◽

Germ Cell Tumors ◽

Optimal Dose ◽

Complete Response ◽

Salvage Chemotherapy ◽

High Dose ◽

Prognostic Features ◽

Conventional Dose ◽

Previously Treated

Purpose To evaluate the optimal dose of carboplatin as well as the efficacy and tolerability of sequential, dose-intense chemotherapy with paclitaxel and ifosfamide followed by carboplatin and etoposide (TICE) plus peripheral-blood stem-cell (PBSC) support in patients with germ cell tumors (GCT) who are likely to experience treatment failure with conventional-dose salvage treatment. This prospective trial followed a similarly designed report of TICE, which used a different means of carboplatin dosing. Patients and Methods The 48 patients entered onto this trial had progressive GCT and unfavorable prognostic features after chemotherapy. Two cycles of paclitaxel plus ifosfamide were administered with leukapheresis, followed by three cycles of carboplatin plus etoposide with reinfusion of PBSC. Results Twenty-three (49%) of 47 assessable patients achieved a complete response (CR) to chemotherapy. An additional three patients (6%) achieved a CR to chemotherapy and surgery. The CR rate was 55%. Six patients experienced relapse, but 24 patients (51%) are alive and free of disease at a median follow-up time of 40 months. Four patients who experienced relapse or achieved an incomplete response were rendered disease free by salvage surgical resection. When combined with results of the prior trial of similar design, TICE chemotherapy yielded an overall CR of 56% (n = 84), with 50% of patients alive with no evidence of disease. Conclusion TICE is an effective and tolerable dose-intense treatment for patients with previously treated metastatic GCT who have a poor predicted outcome to conventional-dose salvage chemotherapy.

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Sequential Dose-Intensive Paclitaxel, Ifosfamide, Carboplatin, and Etoposide Salvage Therapy for Germ Cell Tumor Patients

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.6.1173 ◽

2000 ◽

Vol 18 (6) ◽

pp. 1173-1180 ◽

Cited By ~ 141

Author(s):

Robert J. Motzer ◽

Madhu Mazumdar ◽

Joel Sheinfeld ◽

Dean F. Bajorin ◽

Homer A. Macapinlac ◽

...

Keyword(s):

Germ Cell ◽

Salvage Therapy ◽

Germ Cell Tumors ◽

Complete Response ◽

High Dose ◽

Pharmacokinetic Studies ◽

Target Area ◽

Prognostic Features ◽

Conventional Dose ◽

Durable Complete Response

PURPOSE: To evaluate the efficacy and toxicity of sequential, dose-intensified chemotherapy with paclitaxel/ifosfamide and carboplatin/etoposide administered plus peripheral blood–derived stem-cell (PBSC) support for patients with germ cell tumors (GCT) who have unfavorable prognostic features in response to conventional-dose salvage programs. Carboplatin was dose escalated by target area under the curve (AUC; in [milligrams per milliliter] × minutes) among patient cohorts, and pharmacokinetic studies were performed for comparison. PATIENTS AND METHODS: Thirty-seven previously treated patients who had cisplatin-resistant GCT and unfavorable prognostic features for response to conventional-dose salvage therapy were treated. Two cycles of paclitaxel 200 mg/m2 plus ifosfamide 6 g/m2 were given 2 weeks apart with leukapheresis, followed by three cycles of carboplatin plus etoposide given 14 to 21 days apart with reinfusion of PBSCs. The dose of etoposide was 1,200 mg/m2, and the carboplatin target AUC ranged among cohorts from 12 to 32 (mg/mL) × min. Pharmacokinetic studies of carboplatin were performed for comparison of target to measured AUC. RESULTS: Twenty-one patients (57%) achieved a complete response and an additional two patients (5%) achieved a partial response with normal tumor markers; therefore, 23 (62%) achieved a favorable response. Eight patients relapsed, and 15 (41%) of the favorable responses remained durable at a median follow-up of 30 months. Myelosuppression was the major toxicity; 58% of carboplatin/etoposide cycles were associated with hospitalization for nadir fever. The AUC of carboplatin measured in serum was lower than the target AUC; this may be related to underestimation of the glomerular filtration rate used in the dosing formula. CONCLUSION: Dose-intense therapy with sequential, accelerated chemotherapy of paclitaxel/ifosfamide and carboplatin/etoposide administered with PBSC support was relatively well tolerated. The durable complete response proportion was substantial in patients with unfavorable prognostic features for achieving durable complete response to conventional-dose salvage programs. Optimal dosing of carboplatin in the high-dose setting warrants further investigation.

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High Dose Thiotepa in Patients with Relapsed or Refractory Osteosarcomas: Experience of the SFCE Group

Sarcoma ◽

10.1155/2014/475067 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 6

Author(s):

Perrine Marec-Berard ◽

Céline Segura-Ferlay ◽

Marie-Dominique Tabone ◽

Helene Pacquement ◽

Cyril Lervat ◽

...

Keyword(s):

Stem Cell ◽

Residual Disease ◽

Randomized Study ◽

Progression Free Survival ◽

Salvage Chemotherapy ◽

Paediatric Oncology ◽

High Dose ◽

French Society ◽

Stem Cell Rescue ◽

First Relapse

Introduction. Osteosarcoma relapse has a poor prognosis, with less than 25% survival at 5 years. We describe the experience of the French Society of Paediatric Oncology (SFCE) with high dose (HD) thiotepa and autologous stem cell transplantation (ASCT) in 45 children with relapsed osteosarcoma.Patients and Methods. Between 1992 and 2004, 53 patients received HD thiotepa (900 mg/m2) followed by ASCT in 6 centres. Eight patients were excluded from analysis, and we retrospectively reviewed the clinical radiological and anatomopathological patterns of the 45 remaining patients.Results. Sixteen girls and 29 boys (median age, 15.9 years) received HD thiotepa after initial progression of metastatic disease (2), first relapse (26), and second or third relapse (17). We report 12 radiological partial responses and 9 of 31 histological complete responses. Thirty-two patients experienced further relapses, and 13 continued in complete remission after surgical resection of the residual disease. Three-year overall survival was 40%, and 3-year progression-free survival was 24%. Delay of relapse (+/− 2 years from diagnosis) was a prognostic factor (P=0.011). No acute toxic serious adverse event occurred.Conclusion. The use of HD thiotepa and ASCT is feasible in patients with relapsed osteosarcoma. A randomized study for recurrent osteosarcoma between standard salvage chemotherapy and high dose thiotepa with stem cell rescue is ongoing.

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Paclitaxel, Ifosfamide, and Cisplatin Second-Line Therapy for Patients With Relapsed Testicular Germ Cell Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.12.2413 ◽

2000 ◽

Vol 18 (12) ◽

pp. 2413-2418 ◽

Cited By ~ 179

Author(s):

Robert J. Motzer ◽

Joel Sheinfeld ◽

Madhu Mazumdar ◽

Manjit Bains ◽

Tania Mariani ◽

...

Keyword(s):

Germ Cell ◽

Salvage Therapy ◽

Complete Response ◽

Second Line ◽

Second Line Therapy ◽

Testicular Germ Cell ◽

Primary Tumor Site ◽

Prognostic Features ◽

Line Therapy ◽

Response To Chemotherapy

PURPOSE: To evaluate the dose, toxicity, and efficacy of paclitaxel in combination with ifosfamide and cisplatin as salvage therapy for patients with relapsed testicular germ cell tumors (GCTs). PATIENTS AND METHODS: Thirty patients with previously treated GCTs were treated with paclitaxel and ifosfamide plus cisplatin (TIP) as second-line therapy. All had favorable prognostic features for response (testis primary tumor site and prior complete response to first-line chemotherapy program). Four cycles of paclitaxel, ifosfamide 5 g/m2, and cisplatin 100 mg/m2 were given 21 days apart with granulocyte colony-stimulating factor support, followed by resection of radiographic residua. The dose of paclitaxel was increased among cohorts with dose levels of 175, 215, and 250 mg/m2; the largest dose was selected for the phase II part of the trial. RESULTS: Twenty-three (77%) of 30 patients achieved a complete response to chemotherapy alone, and one patient achieved a durable partial response with normal tumor markers. Therefore, 24 (80%) achieved a favorable response. Eleven patients with normalized markers after chemotherapy underwent resection of residual tissue, with only necrosis found in 10 and mature teratoma in one. Two patients relapsed, and 22 (73%) of the favorable responses remain durable at a median follow-up duration of 33 months. Myelosuppression was the major toxicity, and two patients had grade 3 neurotoxicity. CONCLUSION: Four cycles of TIP was associated with a high proportion of patients who achieved a complete response, a lack of relapse, and relative tolerability as an ifosfamide-containing salvage regimen for testicular GCTs. The high durable complete response proportion emphasizes the importance of patient selection according to prognostic factors for a favorable outcome to conventional-dose salvage therapy.

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Determination of efficacy of TIP combination (paclitaxel, ifosfamide, cisplatin) as first salvage therapy for patients with relapsed germ cell tumors in a poor prognosis group

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e16049 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e16049-e16049

Author(s):

J. Mardiak ◽

K. Rejlekova ◽

M. Mego ◽

J. Rajec ◽

Z. Sycova-Mila ◽

...

Keyword(s):

Germ Cell ◽

Salvage Therapy ◽

Poor Prognosis ◽

Chemotherapy Regimen ◽

Germ Cell Tumors ◽

Complete Response ◽

Good Prognosis ◽

Prognostic Features ◽

Patients With Poor Prognosis

e16049 Background: The efficacy of TIP appears to be suitable salvage therapy for patients with relapsed germ cell tumors (GCTs) with good prognostic features.The aim of our study was to determine the efficacy of TIP as first salvage therapy for patients with relapsed GCTs with poor prognostic features. Methods: Thirty seven patients with relapsed GCTs were treated with TIP as first salvage therapy. Sixteen (43%) patients had favorable prognostic features for response (testis primary tumor site and prior complete response to induction chemotherapy regimen) and 21 (57%) patients had poor prognostic features (either extragonadal site or incomplete response to induction chemotherapy regimen). Four cycles of paclitaxel (175 to 250 mg/m2), ifosfamide 6 g/m2, and cisplatin 100 mg/m2 were given 21 days apart with GC-SF support, followed by resection of resectable radiographic residua. Results: Ten (69%) out of 16 patients with good prognostic features achieved a favorable response to TIP, and all 10 (100%) patients achieved complete response (CR). Six (60%) of the favorable responses remain durable at a median follow-up of 50,6 months. 9 (43%) of 21 patients with poor prognosis achieved a favorable response to chemotherapy, from whom only 1 (10%) patient achieved CR, but 5 patients achieved durable response at a median follow-up duration of 60,6 months. Estimated 2-year overall survival rate (OS) for patients with good prognosis was 56% (95 % CI 54–100%) and 33% (95% CI 21–68%) for patients with poor prognosis. Despite this results, estimated 5-year OS was even more positive for patients with poor prognosis 19% (95% CI 15–61%) comparing to 13% (95% CI 23–80%) for patients with good prognosis. Conclusions: Demonstrated long-term survival of patients with poor prognosis in our nonrandomised study with limited number of patients refers to the TIP being suitable therapy also for patients with relapsed GCTs with poor prognosis. These results warrant the need to continue investigation of real effectiveness of TIP as a first salvage therapy even for patients with poor prognostic features. No significant financial relationships to disclose.

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Survival and toxicity outcomes in patients age 40 or older with relapsed metastatic germ cell tumors (mGCT) treated with high-dose chemotherapy (HDCT) and autologous peripheral-blood stem cell transplant (PBSCT).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.522 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 522-522

Author(s):

Nabil Adra ◽

Costantine Albany ◽

Rafat Abonour ◽

Mohammad Issam Abu Zaid ◽

Dannillo Pereira ◽

...

Keyword(s):

Salvage Therapy ◽

Germ Cell Tumors ◽

Progression Free Survival ◽

High Dose Chemotherapy ◽

High Dose ◽

Cell Transplant ◽

Indiana University ◽

Free Survival ◽

Kaplan Meier

522 Background: HDCT plus PBSCT is effective salvage therapy for relapsed mGCT but has potential toxicity which can be more pronounced in older patients. We report survival and toxicity outcomes in pts with relapsed mGCT age ≥ 40 at time of HDCT. Methods: 440 consecutive pts with relapsed mGCT were treated with HDCT and PBSCT with tandem cycles at Indiana University (IU) between 2004-2017 per our previous reported regimen (N Engl J Med 2007; 357: 340-8). Kaplan-Meier methods were used for progression free survival (PFS) analysis. Results: 110 pts were age ≥ 40 while 330 pts were age < 40. Among pts age ≥ 40, median AFP was 6.6 (range, 1-2,709) and median hCG was 5.3 (range, 1-42, 453). Of the 110 pts age ≥ 40, 75 had complete remission without relapse during a median follow-up of 23 months. There were 3 treatment-related deaths. Conclusions: HDCT plus PBSCT is safe and effective salvage therapy in pts age ≥ 40 with relapsed mGCT. [Table: see text]

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High-dose chemotherapy (HDCT) and peripheral-blood stem cell transplant (PBSCT) in patients age 40 or older with relapsed metastatic germ-cell tumors (mGCT).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e17054 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e17054-e17054

Author(s):

Vaibhav Agrawal ◽

Sandra K. Althouse ◽

Rafat Abonour ◽

Mohammad Issam Abu Zaid ◽

Cheryl K Sullivan ◽

...

Keyword(s):

Salvage Therapy ◽

Multivariable Analysis ◽

Age Groups ◽

Germ Cell Tumors ◽

Progression Free Survival ◽

High Dose ◽

Cell Transplant ◽

Platinum Refractory ◽

Treatment Related Mortality ◽

Related Mortality

e17054 Background: HDCT plus PBSCT is effective salvage therapy for relapsed mGCT but has potential toxicity. Historically, age ≥ 40 years has been associated with greater toxicity and worse outcomes. Methods: 445 consecutive pts with relapsed mGCT were treated with HDCT and PBSCT with tandem cycles at Indiana University from between 2004-2017 per our institutional regimen ( N Engl J Med 2007; 357:340-8). Kaplan-Meier methods and log-rank tests were used for progression free survival (PFS) analysis. Results: 329 pts were age < 40 while 116 pts were age≥40 and HDCT was being used as 2nd line in 85% and 79%, respectively. Median follow-up time was 42.5 months (range 0.3-173.4). Pulmonary metastasis was more frequent in the age < 40 group (66% vs. 41%, P < 0.001). Patients age≥40 were more likely to have seminoma (45% vs. 14%, P < 0.001), were more likely not platinum refractory (80% vs. 63%, P = 0.0010), and were less likely to complete 2 planned tandem cycles of HDCT (86% vs. 93%, P = 0.03). Grade 3 or higher toxicities were similar between either cohort, except for greater pulmonary toxicity in age≥40 group (8% vs. 2%, P = 0.02). Treatment-related mortality was similar between both age groups: 10 patients (3%) in age < 40 and 4 patients (3.5%) in age≥40 group died from complications of HDCT. 2-year PFS for age < 40 vs. age ≥ 40 was 58.7% vs. 59.6% (P = 0.76) and 2-year OS was 63.9% vs. 61.5% (P = 0.93). When evaluating patients with pure seminoma: 2- year OS for age < 40 vs. 40-50 vs. ≥ 50 was 100% vs 90.3%, vs 81.4%, respectively (P = 0.09). For patients with non-seminoma: 2-year OS was 58.1% vs. 37.1% vs. 54.2%, respectively (P = 0.01). In multivariable analysis for PFS: significant factors predicting worse outcomes included platinum refractory disease (HR = 1.55, P = 0.03), primary mediastinal non-seminoma (HR = 2.41, P = 0.03), not completing 2 cycles of HDCT (HR = 2.47, P = 0.01), and hCG > 1000 at initiation of HDCT (HR = 1.92, P < 0.001). Age was not a significant factor predicting worse outcomes. Conclusions: HDCT plus PBSCT is effective salvage therapy in pts age≥40 with relapsed mGCT. Patients age > 40 experience similar rates of toxicity and treatment-related mortality as those < 40 years of age.

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GDP (Gemcitabine, Dexamethasone, Cisplatin) Salvage Therapy Results in Superior Progression Free Survival Compared to Mini-Beam Prior to Autologous Stem Cell Transplantation for Relapsed or Refractory Hodgkin’s Lymphoma.

Blood ◽

10.1182/blood.v104.11.905.905 ◽

2004 ◽

Vol 104 (11) ◽

pp. 905-905 ◽

Cited By ~ 1

Author(s):

John Kuruvilla ◽

Tracy Nagy ◽

Melania Pintilie ◽

Armand Keating ◽

Michael Crump

Keyword(s):

Stem Cell ◽

Salvage Therapy ◽

Progression Free Survival ◽

Salvage Chemotherapy ◽

Hodgkin's Lymphoma ◽

High Dose ◽

High Dose Therapy ◽

Free Survival ◽

Dose Therapy ◽

Cd34 Cells

Abstract Objectives: To compare the response rates and early progression free survival (PFS) after high-dose therapy and autologous stem cell support (ASCT), following salvage chemotherapy with either GDP (gemcitabine 1000 mg/m2 IV d1 & 8, dexamethasone 40 mg PO d1-4, cisplatin 75 mg/m2 day 1) q 3 weeks or mini-BEAM (MB: BCNU, etoposide, cytarabine, melphalan) q3-4 weeks in patients (pts) with relapsed or refractory Hodgkin’s lymphoma. Material and methods: Sixty-eight consecutive pts referred for salvage therapy (34 MB, 34 GDP) were retrospectively compared. All had received prior ABVD chemotherapy except for 3 GDP pts (one received MOPP, one Stanford V, one MOPP/ABV). MB administration required admission to hospital wherease GDP was given in the outpatient setting. Pts typically received 2 cycles of salvage therapy; responding patients had PBSCs mobilized with cyclophosphamide 2 g/m2 day 1, etoposide 200 mg/m2 days 1–3 and filgrastim 10μg/kg. PBSC collection commenced when the blood CD34 cell count was >5–10/μL. Target PBSC number was ≥5 x 106 CD34+ cells/kg and a minimum threshold of 2 x 106 CD34+ cells/kg was required to proceed to high dose therapy (etoposide 60 mg/kg day −4, melphalan160 mg/m2 day −3; PBSC infusion day 0). Pts with bulk disease at relapse > 5cm received involved field radiation (RT) post-ASCT (7/30 GDP pts and 7/28 MB pts). Results: The MB and GDP groups were similar in stage at relapse (limited stage 38% in each group) and disease status (primary refractory: MB 47%, GDP 53%). Ps receiving GDP were older (mean age 43y, range 19–64, vs. MB: mean 34, range 19–60), while more MB pts had previous RT (48% vs. 24%, p=0.03). There were slightly more male pts that received MB versus GDP (M:F MB 24:10, GDP 17:17). The response rate to GDP prior to ASCT (CR, CRu or PR) was 62% (95% CI: 45%–78%) vs. 68% for MB (95% CI: 52%–83%, p=0.61). Nine and 5 pts had stable disease, and 4 and 6 pts progressed on GDP and MB, respectively. 30/34 pts receiving GDP and 28/34 MB pts proceeded to PBSC mobilization. The proportion of pts who had PBSC collections > 2 x 106 CD34+ cells/kg was 97% after GDP vs. 82% after MB (p=0.07), and the proportion collected in a single apheresis procedure was 90% vs 57% (p=0.0043). The proportion of pts who reached the PBSC target of ≥ 5 x 106 CD34+ cells/kg was 97% after GDP and 57% after MB (p=0.0003), and was obtained in a single apheresis more often after GDP (73% vs 36%, p=0.004). Bone marrow harvest was needed in 1 GDP pt (3%) and 5 MB pts (18%, p=0.07). After a median follow up of 1.8 yrs post ASCT for all pts (GDP: 1.2 yrs, range 0.3 – 2.8 yrs; MB: 3 years, range 1.2 – 4.6 yrs), PFS is significantly better for pts receiving GDP compared to MB (74% vs. 35% at 1.5 years, p=0.005). Overall survival at 1.5 yrs is 91% for GDP pts and 82% for MB (p=0.23). Conclusions: Although this is a retrospective analysis, response to and early PFS post-ASCT after GDP compares favourably to MB salvage chemotherapy, our previous standard. Pts receiving GDP have higher PBSC yields, are more likely to have an optimal collection after a single leukapheresis and less likely to experience mobilization failure than pts receiving MB salvage. Based on these data, a phase III trial comparing GDP to MB or dexa-BEAM is warranted.

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Salvage Therapy of Progressive and Recurrent Hodgkin’s Disease: Results From a Multicenter Study of the Pediatric DAL/GPOH-HD Study Group

Journal of Clinical Oncology ◽

10.1200/jco.2005.07.930 ◽

2005 ◽

Vol 23 (25) ◽

pp. 6181-6189 ◽

Cited By ~ 76

Author(s):

Günther Schellong ◽

Wolfgang Dörffel ◽

Alexander Claviez ◽

Dieter Körholz ◽

Georg Mann ◽

...

Keyword(s):

Salvage Therapy ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Disease Free Survival ◽

High Dose Chemotherapy ◽

Primary Treatment ◽

Salvage Chemotherapy ◽

Late Relapse ◽

High Dose ◽

First Relapse

Purpose To evaluate a salvage therapy (ST-HD-86) for patients with progressive and relapsed Hodgkin’s disease after primary treatment in the pediatric DAL/GPOH studies. The essential chemotherapeutic regimens were ifosfamide, etoposide, and prednisone (IEP) and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Methods One hundred seventy-six patients with progression (n = 51) or first relapse (n = 125) were enrolled by 67 centers. The median time from initial diagnosis to progression/relapse was 1.1 year (range, 0.1 to 15.3 years), and the patients’ median age was 14.7 years (range, 4.3 to 24.5 years). Salvage chemotherapy consisted of two to three cycles of IEP alternating with one to two cycles of ABVD supplemented in part by one to two cycles of cyclophosphamide, vincristine, procarbazine, and prednisone or lomustine (CCNU), etoposide, and prednimustine. Radiotherapy was given to involved areas using individualized doses. In the 1990s, additional high-dose chemotherapy with autologous stem-cell transplantation (SCT) was introduced for patients with unfavorable prognosis. Results Disease-free survival (DFS) and overall survival (OS) after 10 years are 62% and 75%, respectively (SE, 4% each). Of 176 patients, 73 suffered second events. The risk-factor analysis revealed the time to progression/relapse as the strongest prognostic factor (P = .0001). Patients with progression have an inferior outcome (DFS, 41%; OS, 51%), whereas patients with late relapse (> 12 months after end of therapy) do well (DFS, 86%; OS, 90%), although none of them received SCT in second remission. Conclusion The result can be considered favorable. Whereas the salvage strategy for progressive disease has to be optimized further, it is possible to reduce intensity and avoid SCT in late relapses after Hodgkin’s disease in childhood/adolescence.

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SS-5 Current management of primary central nervous system lymphoma

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa143.006 ◽

2020 ◽

Vol 2 (Supplement_3) ◽

pp. ii2-ii2

Author(s):

Kazuhiko Mishima ◽

Mitsuaki Shirahata ◽

Junichi Adachi ◽

Tomonari Suzuki ◽

Eita Uchida ◽

...

Keyword(s):

Kinase Inhibitor ◽

Standard Dose ◽

Alkylating Agents ◽

Central Nervous System Lymphoma ◽

Progression Free Survival ◽

Complete Response ◽

High Dose Chemotherapy ◽

Common Adverse Event ◽

High Dose ◽

Newly Diagnosed

Abstract Primary CNS Lymphomas (PCNSLs) is a highly aggressive malignant tumor with poor prognosis and increasing incidence in elderly patients. High-dose methotrexate (HD-MTX) followed by whole-brain radiation therapy (WBRT) improves survival in PCNSLs. Several HD-MTX–based regimens, in combination with alkylating agents and rituximab, have been developed that can achieve high and durable complete response rates in patients with newly diagnosed PCNSL. In Japan, the R-MPV regimen using rituximab, HD-MTX, procarbazine, and vincristine has been recognized as the standard treatment for initial induction for newly diagnosed PCNSL. The optimal consolidative therapy for patients with disease responsive to induction chemotherapy is not yet defined. WBRT at standard dose (30–45 Gy) has a risk of neurotoxicity. To minimize the effects of delayed neurotoxicity, high-dose chemotherapy supported by autologous stem cell transplantation, reduced dose WBRT (23.4Gy), non-myeloablative chemotherapy, and maintenance chemotherapy have been addressed in large randomized trials. Gene expression profiling has provided insights into the pathogenesis of PCNSL. Recent insight into the pathophysiology of PCNSL has led to the investigation of targeted agents in the treatment of recurrent disease. In March 2020, Tirabrutinib (TIR), a second-generation oral Bruton’s tyrosine kinase inhibitor, was approved for relapsed or refractory PCNSL based on the results of the phase I/II study in Japan. Seventeen of 44 patients treated with TIR at 480 mg fasted QD, an approved dose, had overall response rate of 52.9%, median progression-free survival of 5.8 months, and time to response as short as 0.92 months. The most common adverse event at any grade was rash (32%). The skin-related disorders were manageable with appropriate skin treatments. However, greater attention and management is needed the case of more rare adverse events such as severe skin-related disorders and pneumocystis pneumonia. This lecture aims to present the recent development in treatment for PCNSL.

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