A salvage chemotherapy of R‐P‐IMVP16/CBDCA consisting of rituximab,methylprednisolone, ifosfamide,methotrexate, etoposide,and carboplatin for patients with diffuse large B cell lymphoma who had previously received R‐CHOP therapy as first‐line chemotherapy

We have reported the efficacy of the salvage chemotherapy P‐IMVP16/CBDCA for patients with diffuse large B cell lymphoma (DLBCL) who had previously received CHOP before the availability of rituximab (R). Here, we confirmed the efficacy of R combined with P‐IMVP16/CBDCA as a salvage chemotherapy for patients with DLBCL, who had previously received R‐CHOP. We retrospectively analysed 59 patients with relapse or refractory DLBCL (38 male patients and 21 female patients) presenting between June 2004 and June 2013. The patients received R 375 mg/m² on day 1, methylprednisolone 1000 mg/body for 3 days (from day 3 to day 5), ifosfamide 1000 mg/m² for 5 days (from day 3 to day 7), methotrexate 30 mg/m² on day 5 and day 12, etoposide 80 mg/m² for 3 days (from day 3 to day 5), and carboplatin 300 mg/m² on day 3 every 21 days. Patients aged 70 years or older were given 75% of the standard dose. The overall response rate (complete response + partial response) was 64.4%. The 2‐year overall survival rate was 55.3%. The 2‐year progression free survival rate was 34.7%. The 2‐year overall survival rate was 61.5% for the relapse patients, and 15.6% for the refractory patients (p < 0.0001). One patient died because of sepsis related to the treatment regimen. Non‐hematological adverse effects were mild and tolerable. The R‐P‐IMVP‐16/CBDCA regimen displayed a significant activity in relapsed DLBCL, with acceptable toxicity, and should be considered a candidate for salvage chemotherapy. Copyright © 2016 John Wiley & Sons, Ltd.     

Hyperfractionated radiation therapy in Burkitt's lymphoma: a reconsideration aspect

Burkitt's lymphoma (BL) is an aggressive non‐Hodgkin's B‐cell lymphoma with an extremely short doubling time that often presents in extra nodal sites or as an acute leukaemia. Nowadays, with the rapid response to chemotherapy and the diffuse nature of BL, there is no established role for radiation therapy (RT) even in localized disease. Regarding the relapsed/refractory BL, the treatment recommendations remain undefined. We present a 56‐year‐old woman, diagnosed with BL refractory to 6 cycles of R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone), who had disease progression on R‐DHAP (rituximab, dexamethasone, high dose cytarabine and cisplatin) with intrathecal methotrexate, then a partial response on RICE (rituximab, ifosfamide, carboplatin and etoposide). Patient received high dose chemotherapy and autologous haematopoietic stem cell transplantation. Then, she was treated with hyperfractionated involved‐field RT regimen. Currently, the patient remains disease free for around 2 years after remission. We acknowledge that RT is not a standard treatment of BL, especially in patients who attain complete response (CR) after first‐line multi‐agent chemotherapy or even in those who have a CR after second‐line chemotherapy pre‐transplant. Yet, the use of a superfractionated regimen of consolidative radiation could be justified in the treatment of recurrent/refractory localized BL who do not achieve a CR even with second‐line salvage chemotherapy. Radiation therapy in this context, given that it is a well‐tolerated treatment, is a modality worthy of being re‐considered in relapsed/refractory BL. Copyright © 2016 John Wiley & Sons, Ltd.     

Platine and cytarabine-based salvage treatment for primary central nervous system lymphoma

The aim of this study was to evaluate the efficacy and toxicity of two chemotherapy regimens based on platinum and cytarabine in association with etoposide and methylprednisolone (ESHAP) or with dexamethasone (DHAP) with or without Rituximab (± R) in patients with refractory or a relapsed Primary Central Nervous System Lymphoma (PCNSL). All consecutive patients from two French centers with refractory or relapsed PCNSL treated with ESHAP/DHAP ± R were included. We analyzed the overall response rate (ORR), toxicity and overall survival (OS) after salvage chemotherapy. Intensive chemotherapy and hematopoietic stem cell rescue (IC + HCR) was offered to patients less than 65 years of age and consisted of high-dose thiotepa, busulfan and cyclophosphamide. These results were compared with two previously reported series of PCNSL patients treated with the CYVE (high-dose cytarabine and etoposide) regimen at relapse. Twenty-two patients received a total of 60 DHAP/ESHAP cycles (median 3; range 1–5). The median age was 59 years. The ORR after salvage chemotherapy was 59%. Toxicity was mainly hematological, 18% of patients showing febrile neutropenia. There was no treatment-related death. ESHAP or DHAP regimens led to similar ORRs compared to the CYVE regimen in relapsed or refractory PCNSL, although they seemed less toxic. The therapeutic results of the ESHAP/DHAP regimens in relapsed or refractory PCNSL were also similar to those for relapsed systemic non-Hodgkin’s lymphomas (sNHL). Both chemotherapies, CYVE regimen and ESHAP/DHAP are treatment options to be considered in relapsed or refractory PCNSL, especially when IC + HCR is planned as a consolidation treatment. More efforts are still needed to improve the ORR at relapse.     

Successful administration of rituximab-bendamustine regimen in the relapse of Hodgkin lymphoma after autologous hemopoietic stem cell transplantation

Objectives. Treatment options for relapsing Hodgkin lymphoma (HL) are controversial after autologous hemopoietic stem cell transplantation (HSCT). Nevertheless, allogeneic HSCT may be curative if it is performed in complete remission. Case report. In 2007, a 22‐year‐old female patient was diagnosed with nodular sclerosis subtype of classical HL. Her clinical stage was IIAX with unfavorable prognosis. Eight courses of doxorubicin, bleomycin, vinblastine and dacarbazine chemotherapy and involved field irradiation were applied, but after 3 months of complete remission, disseminated relapse was recognised by ¹⁸FDG‐PET/CT. After two cycles of salvage dexamethasone, cisplatinum, and cytosine arabinoside therapy, further progression was noticed, so the treatment was modified to ifosfamide, gemcitabine, vinorelbine, and prednisone (IGEV) regimen. After two cycles of IGEV regimen, she achieved a complete metabolic remission, which was confirmed by a ¹⁸FDG‐PET/CT scan again. She was referred for autologous‐HSCT, and a successful stem cell collection was performed in August 2008. However, a rapid progression was detected again, so total body irradiation was applied before the conditioning therapy with R‐mini‐BEAM regimen. The ¹⁸FDG‐PET/CT scan performed 100 days after the autologous‐HSCT was still positive. In December 2009, multiple nodal and extranodal progression was detected, so ifosfamide, carboplatine, etoposide, mesna protection rescue treatment was started, but it was ineffective. Based on sporadic data of the literature, rituximab–bendamustine therapy was started in March 2010. After four cycles, she achieved complete metabolic remission, which was verified by ¹⁸FDG‐PET/CT. The patient has been referred for an allogeneic HSCT with reduced intensity conditioning. Conclusions. Based on our experience, bendamustine–rituximab salvage therapy can be a suitable option for the treatment of post‐transplant progression or relapse of HL. Copyright © 2011 John Wiley & Sons, Ltd.     

High dose chemotherapy with autologous stem cell support in the treatment of germ cell tumors: experience of the centre Léon-Bérard between 1982 and 1996]

More than 80% patients with metastatic germ cell tumors are cured by chemotherapy and surgery. Since 1980, intensive chemotherapy with autologous bone marrow was developed for the patients who where not cured by conventional chemotherapy. We present the experience of the Centre Léon-Bérard, between 1982 and 1996, seventy-five metastatic germ cell tumors patients were treated with high dose chemotherapy and autologous stem cell support. Forty-six patients received cisplatin, etoposide, ifosfamide (VIC regimen), 17 carboplatin, etoposide, cyclophosphamide (CarboPEC regimen), 9 cisplatin, etoposide, cyclophosphamide (PEC) and 10 had another regimen. The chemotherapy was administred in different situations: 31 patients with poor prognosis in first line, 15 in salvage of sensitive relapse, 15 in salvage of incomplete response, and 14 with a cisplatin refractory disease. The complete response rate was 31% among the 54 evaluable patients. Seven patients died as a consequence of the treatment. The two-year overall actuarial survival and the event free survival were respectively 67% and 57% (median 42 months). Only 2 patients who had a refractory disease are continuously disease-free at 42 and 87 months after regimen. The renal toxicity was more severe with regimen VIC than with CarboPEC 30% versus 60%, whereas the hematologic toxicity are similar with both. This study shows the feasability of high dose chemotherapy. Two refractory patients are alive, and the results seem to be interesting for the patients in salvage treatment. But this treatment is not a standard for germinal cell tumors and randomized trials are ongoing.     

Rituximab,methotrexate, procarbazine,vincristine and intensified cytarabine consolidation for primary central nervous system lymphoma (PCNSL) in the elderly: a LOC network study

Primary CNS lymphoma (PCNSL) is chemosensitive to high-dose methotrexate-based chemotherapy. However, responses in the elderly are short-lasting and outcome is poor. Given that radiotherapy and intensive chemotherapy expose elderly to severe toxicities, alternative consolidation approaches need to be evaluated. In this multicenter study, we retrospectively analyzed consecutive patients with newly-diagnosed PCNSL, aged >60, treated with a (R)-MPV-AAA regimen. The regimen consisted of three 28-day cycles of methotrexate (3.5 g/m² D1, D15), procarbazine, vincristine, followed by three 28-day cycles of cytarabine consolidation (3 g/m² D1-2). Addition of rituximab (375 mg/m² D1) was optional. The results were compared with the historical MPV-A regimen. Ninety patients received the (R)-MPV-AAA regimen with (n?=?39) or without (n?=?51) rituximab. Median age was 68 and median KPS 60. 55% of patients achieved a complete response, 8% a partial response and 37% progressed. The median PFS was 10 months, the median OS 28.1 months. Toxicity was mainly hematological, with 54 and 51% of grade III-IV neutropenia and thrombopenia. The response rate was higher in patients receiving rituximab (77 vs. 53%; p?=?0.03), whereas no difference was observed in terms of PFS or OS. When comparing the results to the historical MPV-A, there was no difference in terms of response rate, PFS or OS, but a higher rate of hematotoxicity. This study suggests that extending cytarabine consolidation after methotrexate-based chemotherapy does not improve the MPV-A efficacy but increases toxicity in the elderly. The addition of rituximab may improve the response rate, but its impact on final outcome remains unclear.     

Efficacy and safety of the combination of rituximab,fludarabine, and mitoxantrone for rituximab‐naive,recurrent/refractory follicular non‐Hodgkin lymphoma with high tumor burden

BACKGROUND:

This phase 2 trial was undertaken to evaluate the efficacy and safety of rituximab combined with intravenous fludarabine and mitoxantrone (R‐FM) for patients with recurrent/refractory follicular lymphoma who had high tumor burden according to Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria.

METHODS:

Fifty patients were enrolled who had received a maximum of 2 previous regimens, including 1 cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)/CHOP‐like regimen but no previous exposure to rituximab, fludarabine, or mitoxantrone. At baseline, 58% of patients had bulky disease (lesion >7cm), 56% had high‐risk Follicular Lymphoma International Prognostic Index (FLIPI) scores (range, 3‐5), and 22% were refractory. Treatment consisted of 4 courses of R‐FM (rituximab 375 mg/m² intravenously on Day 1, fludarabine 25 mg/m² intravenously on Days 2 through 4, and mitoxantrone 10 mg/m² intravenously on Day 2, recycling at Day 28) and consolidation with 2 courses of fludarabine and mitoxantrone (the same regimen without rituximab).

RESULTS:

The best response (84% overall response rate including 68% complete response/complete response unconfirmed) was achieved after 4 courses of R‐FM. Response rates were high regardless of age, refractoriness to last previous therapy, and FLIPI score. After a median follow‐up of 4 years, the 3‐year progression‐free survival rate was 47%, the event‐free survival rate was 41%, and the 3‐year overall survival rate was 66%. Grade ≥3 neutropenia and infections were the most common toxicities and occurred in 72% and 14% of patients, respectively.

CONCLUSIONS:

Cytoreduction with 4 courses of R‐FM was safe and highly efficient in patients with recurrent/refractory follicular lymphoma who had high tumor burden; however, better consolidation than FM is needed to further improve outcome. Cancer 2010. © 2010 American Cancer Society.     

High-dose rituximab does not negatively affect peripheral blood stem cell mobilization kinetics in patients with intermediate-grade non-Hodgkin's lymphoma

Rituximab, an anti-CD20 human-mouse chimeric monoclonal antibody has been shown to improve response rates when it is combined with standard salvage chemotherapy in patients with relapsed or refractory intermediate-grade B-cell non-Hodgkin's lymphoma. A vast majority of these patients subsequently undergo high-dose therapy followed by stem cell transplantation. However, the impact of rituximab on stem cell mobilization kinetics is not well characterized. The purpose of this study was to study the effect of high-dose rituximab given with chemotherapy on stem cell mobilization in patients with intermediate-grade B-cell non-Hodgkin's lymphoma. Thirty-six patients received ifosfamide, etoposide, and rituximab followed by filgrastim for stem cell mobilization. The chemotherapy regimen was well tolerated. Thirty-four of 36 patients (94%) were able to mobilize at least 2 × 10⁶ CD34+ cells/kg body weight after a median of 2 apheresis procedures. The median CD34+ cell dose collected per kilogram of recipient body weight was 6.5 × 10⁶ (range, 4.65-31.15). All patients who subsequently underwent high-dose chemotherapy and stem cell transplantation experienced sustained engraftment. In conclusion, high-dose rituximab given during stem cell mobilization does not negatively affect stem cell mobilization kinetics.     

Augmented ICE in Patients With Poor-Risk Refractory and Relapsed Lymphomas

BackgroundIn patients with relapsed/refractory lymphoma after first line therapy, chemosensitivity to salvage chemotherapy is the main determinant of outcome pre-autologous stem cell transplant . With novel therapies not yet widely available and poor responses to conventional dose salvage therapy such as ifosfamide, carboplatin, and etoposide (ICE) in patients with early relapse within 12 months and primary refractory disease, there is capacity to dose intensify ifosfamide and etoposide (augmented ICE).MethodsWe retrospectively evaluated patients who received augmented ICE between 2010 and 2020 and report on response, deliverability, toxicities, and outcome. Patients were transplant eligible with diffuse large-B cell lymphoma (DLBCL) or Hodgkin lymphoma (HL) with refractory disease or relapse within 12 months. Dose of augmented ICE versus standard ICE was ifosfamide 10 versus 5 g/m² and etoposide 600 versus 300 mg/m². Carboplatin dose with a calculated area under curve of 5 was unchanged. Anti-CD20 monoclonal antibody was given in patients with CD20 positive lymphoma. Responding patients who achieved complete response or partial response proceeded to transplant.ResultsTwenty-one patients with DLBCL (n = 13) and HL (n = 8) received augmented ICE. Nineteen of 21 completed 2 cycles. Overall response rates were 85% (DLBCL) and 100% (HL). Most patients required transfusion, 2 developed reversible ifosfamide encephalopathy and 86% febrile neutropenia. Eighteen patients proceeded to transplant. 5-year overall survival (OS) and progression-free survival (PFS) in DLBCL were 62% and 45%, and in HL, 100% and 88%, respectively.ConclusionAugmented ICE is associated with high response rate and transplant realization at the expense of toxicity.     

Bendamustine is effective therapy in patients with rituximab‐refractory,indolent B‐cell non‐Hodgkin lymphoma

BACKGROUND:

Bendamustine hydrochloride is a novel alkylating agent. In this multicenter study, the authors evaluated the efficacy and toxicity of single‐agent bendamustine in patients with rituximab‐refractory, indolent B‐cell lymphoma.

METHODS:

Eligible patients (N = 100, ages 31‐84 years) received bendamustine at a dose of 120 mg/m² by intravenous infusion on Days 1 and 2 every 21 days for 6 to 8 cycles. Histologies included follicular (62%), small lymphocytic (21%), and marginal zone (16%) lymphomas. Patients had received a median of 2 previous regimens (range, 0‐6 previous regimens), and 36%were refractory to their most recent chemotherapy regimen. Primary endpoints included overall response rate (ORR) and duration of response (DOR). Secondary endpoints were safety and progression‐free survival (PFS).

RESULTS:

An ORR of 75% (a 14% complete response rate, a 3% unconfirmed complete response rate, and a 58% partial response rate) was observed. The median DOR was 9.2 months, and median PFS was 9.3 months. Six deaths were considered to be possibly treatment related. Grade 3 or 4 (determined using National Cancer Institute Common Toxicity Criteria [version 3.0.19]. reversible hematologic toxicities included neutropenia (61%), thrombocytopenia (25%), and anemia (10%). The most frequent nonhematologic adverse events (any grade) included nausea (77%), infection (69%), fatigue (64%), diarrhea (42%), vomiting (40%), pyrexia (36%), constipation (31%), and anorexia (24%).

CONCLUSIONS:

Single‐agent bendamustine produced a high rate of objective responses with acceptable toxicity in patients with recurrent, rituximab‐refractory indolent B‐cell lymphoma. Cancer 2010. © 2010 American Cancer Society.     

原发性中枢神经系统淋巴瘤的治疗进展

原发性中枢神经系统淋巴瘤（primary central nervous system lymphoma ,PCNSL ）是一种罕见的结外淋巴瘤,其病理类型多为弥漫性大B 细胞淋巴瘤,影像学多表现为单发的脑实质深部病变,MRI 可有多种强化形态。目前,以大剂量甲氨蝶呤为主的化疗已成为PCNSL 的一线治疗。放、化疗的结合可延长患者的生存期,但神经毒性发生率较高。大剂量化疗联合自体干细胞移植对复发/ 难治性PCNSL 有效。替莫唑胺和利妥昔单抗不良反应小、耐受性好,可作为PCNSL 治疗的选择。PCNSL 的预后受血清LDH浓度、年龄、ECOG 评分/KPS 评分、脑脊液蛋白浓度、肿瘤定位等多种因素的影响。     

Intensive dose ifosfamide and etoposide with G-CSF for stem cell mobilization in patients with non-Hodgkin's lymphoma

We studied 36 patients with non-Hodgkin's lymphoma to evaluate the stem cell yield following recovery from intensive dose ifosfamide and etoposide given as mobilization chemotherapy. We also assessed the toxicity of the regimen and engraftment kinetics. All patients had intermediate grade lymphoma and had either failed to achieve a complete remission to induction chemotherapy or had relapsed. Patients received ifosfamide 10 g/m2 IV total dose given over 72 hours, etoposide 150 mg/m2 IV every 12 hours for 6 doses and G-CSF 10 microg/kg/d. Thirty-four patients went on to receive high-dose chemotherapy with BEAM or with CVP and BEAM. A median of 2 (1-10) apheresis was required to reach the target CD34+ count of >4 x 10(6)/kg. A median of 13.1 CD34+ cells/kg (4.1-148) was obtained. Toxicity was limited to mucositis in 3 patients, transient confusion and transient rise in liver function tests in 3 and 2 patients respectively. The median time to engraftment was 10 days (8-17) for all the patients undergoing high-dose chemotherapy. The regimen of intensive dose ifosfamide and etoposide along with G-CSF is well tolerated and in this group of patients has lead to successful stem cell harvests and sustained engraftment.     

Fotemustine-based therapy in combination with rituximab as a first-line induction chemotherapy followed by WBRT for newly diagnosed primary central nervous system lymphoma:a prospective phase Ⅱ trial

Objective: This study aimed to evaluate the safety, efficacy, and feasibility of the rituximab, fotemustine, pemetrexed, and dexamethasone(R-FPD) regimen followed by whole-brain radiotherapy(WBRT) for patients with primary central nervous system lymphoma(PCNSL).Methods: A prospective, single-center phase II clinical trial was conducted. Patients with PCNSL newly diagnosed at the First Affiliated Hospital of Zhengzhou University between July 2018 and July 2020 were studied. The R-FPD regimen cons...     

Salvage ifosfamide-doxorubicin chemotherapy in patients with recurrent nasopharyngeal carcinoma pretreated with cisplatin-based chemotherapy

This study evaluated the efficacy and toxicity of ifosfamide and doxorubicin chemotherapy regimen in Turkish patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) previously treated with platinum-based chemotherapy. Twenty-one patients with recurrent or metastatic NPC previously treated with platinum-based chemotherapy as adjuvant or palliative treatments who received ifosfamide 2500 mg/m² d 1–3, mesna 2500 mg/m² d 1–3, doxorubicin 60 mg/m² d 1, repeated every 21 d was retrospectively analyzed. Patients received a median number of three cycles of ifosfamide-doxorubicin (range: 1–6). Seven patients (33.3%) achieved partial response and no patient achieved complete response. Six (28.5%) had stable disease, whereas three (18.75%) had progressive disease. The median time to progression was 7.0 mo. Ifosfamide-doxorubicin regimen is an effective salvage regimen in patients with recurrent and metastatic NPC.     

Survival following intensive chemotherapy with bone marrow reconstitution for children with recurrent intracranial ependymoma A report of the Children's Cancer Group

Recurrent intracranial ependymoma is rarely cured by surgery, radiotherapy, and chemotherapy in conventional doses. This study was designed to determine the toxicity, radiographic response rate and outcome following intensive chemotherapy with ThioTEPA, etoposide, carboplatinum and autologous bone marrow rescue (ABMR) for young children with recurrent central nervous system ependymoma. ThioTEPA 300 mg/m²/day (total 900 mg/m²) and etoposide 250 to 500 mg/m²/day (total 750 to 1500 mg/m²) were administered for three consecutive days with or without the addition of carboplatinum 500 mg/m²/day (total 1500 mg/m²) for an additional three consecutive days, and autologous bone marrow was reinfused 72 hours following chemotherapy. Eligibility criteria required adequate renal, hepatic and pulmonary function, and no tumor infiltration of bone marrow. Fifteen children with recurrent intracranial ependymoma, aged 5 months to 12 years (median 22 months), were treated. Five patients died of treatment related toxicities within 62 days of marrow reinfusion. Eight have expired from progressive disease a median of six months post-ABMR, and one has died from unrelated causes. One child remains alive 25 months post-ABMR, following further disease recurrence. No partial or complete responses were observed. This regimen of high-dose ThioTEPA and etoposide with or without additional carboplatinum with ABMR is not an effective strategy for retrieving heavily pre-treated children with recurrent ependymoma.     

Mitoxantrone/ifosfamide/etoposide salvage regimen with rituximab for in vivo purging in patients with relapsed lymphoma

Treatment with the anti-CD20 antibody rituximab prior to stem cell collection may lead to tumor-free stem cell collections in patients with B-cell lymphoma undergoing autologous stem cell transplantation. To test the feasibility of obtaining polymerase chain reaction (PCR)-negative stem cell collection, 30 patients with a variety of B-cell lymphomas were enrolled in a protocol employing a common MINE (mitoxantrone/ifosfamide/etoposide) salvage regimen with rituximab (in vivo purging). Rituximab 400 mg/m2 was administered weekly for 3 weeks on days 1, 6, and 8 in relation to the last MINE cycle, which was followed by growth factor-stimulated peripheral stem cell collection. The median number of CD34(+) cells/kg was 2.5 million cells/kg collected over a median of 5 days. Polymerase chain reaction amplification for the t (14;18) or the heavy-chain gene rearrangement was performed prior to treatment and on the leukapheresis sample. Out of 15 patients who had a positive PCR signal prior to treatment, 10 had PCR-negative stem cell collections, whereas 5 had PCR-positive stem cell collections. After high-dose chemotherapy and stem cell transplant, all patients with a PCR-positive signal pretreatment became PCR negative. We conclude that rituximab may increase the yield of tumor-free stem cells. Higher rates of PCR negativity have been reported when more intense and protracted chemoimmunotherapy regimens have been employed. The magnitude of clinical benefit and the significance of the PCR analysis in stem cells after rituximab requires larger studies.     

Bortezomib in combination with rituximab, dexamethasone, ifosfamide, cisplatin and etoposide chemoimmunotherapy in patients with relapsed and primary refractory diffuse large B-cell lymphoma

Patients with relapsed or refractory diffuse large B-cell lymphoma may experience extended survival with second-line chemotherapy and autologous stem cell transplant (ASCT). Since a major determinant of outcome after ASCT is responsiveness to second-line therapy, the development of more effective second-line treatments is desirable. We investigated the addition of bortezomib to rituximab, dexamethasone, ifosfamide, cisplatin and etoposide (VIPER). Fifteen patients were enrolled, of whom seven were refractory to first-line chemotherapy and only three had maintained first response for 1 year. Nine (60%) patients achieved objective responses, of which three (20%) were IWC-PET (International Workshop Criteria positron emission tomography) complete responses. Median progression-free survival was 3 months, and median overall survival was 10 months. At a median follow-up of 26 months, five patients (33%) remained alive. Treatment was well tolerated with no unexpected toxicity. Although response rates did not meet predefined criteria, activity was at least comparable to other second-line approaches despite a poor-prognosis patient population.     

Blood stem cell collections after mobilization with combination chemotherapy containing ifosfamide followed by G-CSF in multiple myeloma

High-dose chemotherapy with autologous peripheral blood stem cell transplantation is the standard treatment of patients with multiple myeloma today. In this study we used a combination mobilizing chemotherapy containing ifosfamide with G-CSF before stem cell collection. The chemotherapy regimen consisted of ifosfamide (2,500 mg/m(2) days 1-3), epirubicin (100 mg/m(2) day 1) and etoposide (150 mg/m(2) days 1-3) followed by G-CSF (5 mug/kg from day 5). In 30 younger patients (median age 51 years; range 41-60 years) who received the IEV regimen in 100% dosage, a median of 11.15 x 10(6) CD34(+) cells/kg (range 0-44.60 x 10(6) CD34(+) cells/kg) was collected. In 22 elder patients (median age 64 years; range 59-72 years) similar collection results were obtained with a median of 10.82 x 10(6) CD34(+) cells/kg (range 0.99-42.22 x 10(6) CD34(+) cells/kg) after the IEV regimen in 75% dosage. The pretreatment chemotherapy cycles before mobilization were fewer in elder patients with a median of 0 cycles (range 0-7 cycles) compared with younger patients with a median of 4 cycles (range 0-7 cycles). These collection results were favorable and allowed to support a tandem transplantation procedure in younger and elder patients in 97 and 95%, respectively. In the majority of patients, the hematological toxicity of IEV was of WHO grade 3/4. The extramedullary toxicity was mild to moderate and there were only few cases (5-10%) of relevant nephrotoxicity or neurotoxicity associated with the application of ifosfamide.     

Tandem high-dose chemotherapy supported by autologous peripheral blood stem cell transplantation for recurrent soft tissue sarcoma

BACKGROUND: Patients with recurrent soft tissue sarcoma (STS) are seldom curable, with 5-year survival rates of less than 10% in all large series. The role of high-dose chemotherapy (HDC) with hematopoietic stem cell support in this disease has not been established. CASE REPORT: We report on two patients with recurrent STS who were treated with tandem HDC supported by autologous peripheral blood stem cell transplantation (PBSCT). One patient with malignant fibrous histiocytoma recurred with multiple lung metastases. This patient achieved a partial response after two cycles of induction chemotherapy consisting of ifosfamide and epirubicin. During four cycles of induction chemotherapy, peripheral blood stem cells (PBSCs) were harvested. Tandem high-dose ICE regimen (ifosfamide 3 g/m2 on days-7 to -3, carboplatin 400 mg/m2 on days-7, -5 and 3, etoposide 500 mg/m2 on days-7, -5 and 3) supported by autologous PBSCT gave rise to further regression of the tumors. Another patient with malignant hemangiopericytoma was treated by tandem high-dose ICE regimen supported by autologous PBSCT after the 3rd removal of abdominal tumors. Relapse-free intervals until the 1st, 2nd and 3rd relapses were 40, 19 and 22 months, respectively. Tandem high-dose ICE regimen might delay the relapse. CONCLUSION: These observations suggest that a tandem high-dose ICE regimen with autologous PBSCT is feasible with some clinical efficacy in the control of refractory STS.     

Dose-intense therapy with etoposide, ifosfamide, cisplatin, and epirubicin (VIP-E) in 107 consecutive patients with limited- and extensive-stage non-small-cell lung cancer

Background: We conducted a phase I/II trial to assess the feasibilityand activity of combination chemotherapy with etoposide, ifosfamide,cisplatin, and epirubicin in limited-stage (LS, stage I–IIIB) andextensive-stage (ES, stage IV) non-small-cell lung cancer (NSCLC). End-pointswere treatment-related morbidity and mortality, response rate, duration ofresponse, and survival.Patients and methods: Chemotherapy followed by granulocytecolony-stimulating factor was given at a dose of etoposide (500mg/m²), ifosfamide (4000 mg/m²), cisplatin (50mg/m²), and epirubicin (50 mg/m²) (VIP-E) to107 patients with NSCLC. Twenty-five patients with qualifying responsesproceeded to high-dose chemotherapy with autologous peripheral blood stem celltransplantation after etoposide (1500 mg/m²), ifosfamide(12,000 mg/m²), carboplatin (750 mg/m²) andepirubicin (150 mg/m²) (VIC-E) conditioning.Results of conventional-dose VIP-E: 35 of 102 (34%) evaluablepatients responded (2 CR's, 33 PR's), 33/102 patients (33%) showed nochange (NC); the remainder of patients progressed with therapy (PD). Objectiveresponse rate was 68% (4% CR, 64% PR) in LS-NSCLC and23% (1.4% CR, 21.4% PR) in ES-NSCLC. Median duration ofsurvival was 13 months in LS-NSCLC and 5.5 months in ES-NSCLC. Two-yearsurvival was 26% in LS and 2% in ES-NSCLC.Results of high-dose VIC-E: 23 of 24 evaluable patients improved ormaintained prior responses (92%), 1 patient showed NC. Treatmentmortality was 4%. Median duration of survival was 17 months in LS-NSCLCand 10 months in ES-NSCLC. Two-year survival was 30% in LS and8% in ES-NSCLC.Conclusion: Response-rates and survival after conventional-dose VIP-Echemotherapy are comparable to other published trials of combinationchemotherapy in NSCLC. Toxicity and mortality is acceptable in limited stage,but unacceptably high in extensive stage NSCLC. Although better response-rateswere achieved in the high-dose arm, they did not translate into improvedsurvival. Most stage IV NSCLC-patients will neither benefit from VIP-Econventional dose, nor from VIC-E high dose chemotherapy. Whether selectedLS-patients with partial or complete responses to VIP-E induction chemotherapycould benefit from dose intensification in an adjuvant or neo-adjuvant settingremains to be determined.