Gemcitabine, cisplatin and methylprednisolone (GEM-P) with or without Rituximab in relapsed and refractory patients with diffuse large B cell lymphoma (DLBCL)

This is the first report of the combination of gemcitabine, cisplatin and methylprednisolone (GEM-P) with Rituximab (GEM-PR) for diffuse large B-cell lymphoma (DLBCL). Thirty-nine patients with relapsed or refractory DLBCL in this study received GEM-P with (n = 24) or without Rituximab (n = 15) 64% patients had Stage III/IV disease. The overall response rate (ORR) was 59% (95% CI 42.1-74.4); 11/39 (28%) patients attained complete response. Patients received a median of two cycles (1-4) of treatment. For GEM-PR group, the ORR was 67% (95% CI 45-84%) compared to 47% (95% CI 21-73%) in GEM-P alone. one-year progression-free survival was 51% (95% CI 28-69%) in GEM-PR group compared to 27% (95% CI 8-49%) in GEM-P alone (P = 0.04). GEM-P is an effective second-line regimen in patients with relapsed or refractory DLBCL and the addition of Rituximab appears to further improve outcomes.     

Gemcitabine,cisplatin and methylprednisolone (GEM-P) with or without Rituximab in relapsed and refractory patients with diffuse large B cell lymphoma (DLBCL)

This is the first report of the combination of gemcitabine, cisplatin and methylprednisolone (GEM-P) with Rituximab (GEM-PR) for diffuse large B-cell lymphoma (DLBCL). Thirty-nine patients with relapsed or refractory DLBCL in this study received GEM-P with (n = 24) or without Rituximab (n = 15) 64% patients had Stage III/V disease. The overall response rate (ORR) was 59% (95% CI 42.1–74.4); 11/39 (28%) patients attained complete response. Patients received a median of two cycles (1–4) of treatment. For GEM-PR group, the ORR was 67% (95% CI 45–84%) compared to 47% (95% CI 21–73%) in GEM-P alone. one-year progression-free survival was 51% (95% CI 28–69%) in GEM-PR group compared to 27% (95% CI 8–49%) in GEM-P alone (P = 0.04). GEM-P is an effective second-line regimen in patients with relapsed or refractory DLBCL and the addition of Rituximab appears to further improve outcomes.     

GEM-P chemotherapy is active in the treatment of relapsed Hodgkin lymphoma

Hodgkin lymphoma (HL) is a relatively chemosensitive malignancy. However, for those who relapse, high-dose chemotherapy with autologous stem cell transplant is the treatment of choice which relies on adequate disease control with salvage chemotherapy. Regimens commonly used often require inpatient administration and can be difficult to deliver due to toxicity. Gemcitabine and cisplatin have activity in HL, non-overlapping toxicity with first-line chemotherapeutics, and may be delivered in an outpatient setting. In this retrospective single-centre analysis, patients with relapsed or refractory HL treated with gemcitabine 1,000 mg/m² day (D)1, D8 and D15; methylprednisolone 1,000 mg D1–5; and cisplatin 100 mg/m² D15, every 28 days (GEM-P) were included. Demographic, survival, response and toxicity data were recorded. Forty-one eligible patients were identified: median age 27. One hundred and twenty-two cycles of GEM-P were administered in total (median 3 cycles; range 1–6). Twenty of 41 (48 %) patients received GEM-P as second-line treatment and 11/41 (27 %) as third-line therapy. Overall response rate (ORR) to GEM-P in the entire cohort was 80 % (complete response (CR) 37 %, partial response 44 %) with 14/15 CR confirmed as a metabolic CR on PET and ORR of 85 % in the 20 second-line patients. The most common grade 3/4 toxicities were haematological: neutropenia 54 % and thrombocytopenia 51 %. Median follow-up from the start of GEM-P was 4.5 years. Following GEM-P, 5-year progression-free survival was 46 % (95 % confidence interval (CI), 30–62 %) and 5-year overall survival was 59 % (95 % CI, 43–74 %). Fourteen of 41 patients proceeded directly to autologous transplant. GEM-P is a salvage chemotherapy with relatively high response rates, leading to successful transplantation in appropriate patients, in the treatment of relapsed or refractory HL.     

Gemcitabine, cisplatin and methylprednisolone for the treatment of patients with peripheral T-cell lymphoma: the Royal Marsden Hospital experience

Novel, effective therapies are needed for peripheral T-cell non-Hodgkin's lymphoma (PTCL). We treated 16 patients with a combination of gemcitabine, cisplatin and methylprednisolone (GEM-P). Three patients (19%) achieved a complete remission and eight (50%) a partial remission. GEM-P has encouraging efficacy with an acceptable toxicity profile in patients with PTCL.     

Autotransplantation for advanced lymphoma and Hodgkin's disease followed by post-transplant rituxan/GM-CSF or radiotherapy and consolidation chemotherapy

Disease relapse occurs in 50% or more of patients who are autografted for relapsed or refractory lymphoma (NHL) or Hodgkin's disease (HD). The administration of non-cross-resistant therapies during the post-transplant phase could possibly control residual disease and delay or prevent its progression. To test this approach, 55 patients with relapsed/refractory or high-risk NHL or relapsed/refractory HD were enrolled in the following protocol: stem cell mobilization: cyclophosphamide (4.5 g/m(2)) + etoposide (2.0 g/m(2)) followed by GM-CSF or G-CSF; high-dose therapy: gemcitabine (1.0 g/m(2)) on day -5, BCNU (300 mg/m(2)) + gemcitabine (1.0 g/m(2)) on day -2, melphalan (140 mg/m(2)) on day -1, blood stem cell infusion on day 0; post-transplant immunotherapy (B cell NHL): rituxan (375 mg/m(2)) weekly for 4 weeks + GM-CSF (250 microg thrice weekly) (weeks 4-8); post-transplant involved-field radiotherapy (HD): 30-40 Gy to pre-transplant areas of disease (weeks 4-8); post-transplant consolidation chemotherapy (all patients): dexamethasone (40 mg daily)/cyclophosphamide (300 mg/m(2)/day)/etoposide (30 mg/m(2)/day)/cisplatin (15 mg/m(2)/day) by continuous intravenous infusion for 4 days + gemcitabine (1.0 g/m(2), day 3) (months 3 + 9) alternating with dexamethasone/paclitaxel (135 mg/m(2))/cisplatin (75 mg/m(2)) (months 6 + 12). Of the 33 patients with B cell lymphoma, 14 had primary refractory disease (42%), 12 had relapsed disease (36%) and seven had high-risk disease in first CR (21%). For the entire group, the 2-year Kaplan-Meier event-free survival (EFS) and overall survival (OS) were 30% and 35%, respectively, while six of 33 patients (18%) died before day 100 from transplant-related complications. The rituxan/GM-CSF phase was well-tolerated by the 26 patients who were treated and led to radiographic responses in seven patients; an eighth patient with a blastic variant of mantle-cell lymphoma had clearance of marrow involvement after rituxan/GM-CSF. Of the 22 patients with relapsed/refractory HD (21 patients) or high-risk T cell lymphoblastic lymphoma (one patient), the 2-year Kaplan-Meier EFS and OS were 70% and 85%, respectively, while two of 22 patients (9%) died before day 100 from transplant-related complications. Eight patients received involved field radiation and seven had radiographic responses within the treatment fields. A total of 72 courses of post-transplant consolidation chemotherapy were administered to 26 of the 55 total patients. Transient grade 3-4 myelosuppression was common and one patient died from neutropenic sepsis, but no patients required an infusion of backup stem cells. After adjustment for known prognostic factors, the EFS for the cohort of HD patients was significantly better than the EFS for an historical cohort of HD patients autografted after BEAC (BCNU/etoposide/cytarabine/cyclophosphamide) without consolidation chemotherapy (P = 0.015). In conclusion, post-transplant consolidation therapy is feasible and well-tolerated for patients autografted for aggressive NHL and HD and may be associated with improved progression-free survival particularly for patients with HD.     

An oxaliplatin-based chemotherapy in patients with relapsed or refractory intermediate and high-grade non-Hodgkin's lymphoma

This study was designed to assess the efficacy and safety of substituting cisplatin with oxaliplatin in the DHAP (dexamethasone, cytarabine and cisplatin) regimen for patients with relapsed or refractory non-Hodgkin's lymphoma. Twenty-four evaluable patients with intermediate or high-grade non-Hodgkin's lymphoma were treated at 3-weekly intervals with oxaliplatin (130 mg/m2, d 1), cytarabine (2 g/m2 for two doses, d 2) and dexamethasone (40 mg, d 1-4). The median age of the patients was 58 (range 18-70). Histological subtypes were diffuse large B cell, 20; mantle cell, two; anaplastic large cell, one; and peripheral T cell, one. The overall objective response rate (RR) was 50% [95% confidence interval (CI) = 29-71%] including four complete responses and eight partial responses. RR for those patients treated at first relapse was higher than those treated at second and subsequent relapse (77% versus 29%). Grade 3 and 4 toxicity was mainly haematological: anaemia 17%, neutropenia 75% and thrombocytopenia 75%. No grade 4 non-haematological toxicity was reported. No significant renal and neurotoxicity was demonstrated. Median survival was 10.6 months. Probabilities of 1-year progression-free survival and overall survival were 47% (95% CI = 26-66%) and 50% (95% CI = 23-72%) respectively. In conclusion, dexamethasone, cytarabine and oxaliplatin (DHAX) is a novel combination in salvage therapy for relapsed or refractory non-Hodgkin's lymphoma. It has clinically significant activity with an acceptable toxicity profile. Lack of renal toxicity makes DHAX an attractive cytoreductive regimen before high-dose chemotherapy.     

Pilot study of an outpatient-based approach for advanced lymphoma using vinorelbine, gemcitabine and filgrastim

Background: Vinorelbine and gemcitabine have demonstrable single‐agent activity against lymphoma, show differing toxicity profiles and can be given in an outpatient setting. Aims: We have evaluated the feasibility of an outpatient‐based combination of vinorelbine and gemcitabine with filgrastim support (VGF) in patients with advanced lymphoma. Methods: An open‐label, single‐arm study of 40 consecutive patients with relapsed (n = 24) or refractory (n = 16) lymphoma was undertaken. The median number of prior regimens was three (range 1–11) and 12 had undergone prior stem cell transplantation. Patients received vinorelbine 25 mg/m² and gemcitabine 1000 mg/m² on days 1 and 8 of each 21‐day cycle. Patients showing no response after two cycles (early response) were offered alternative therapy. Responding patients received two more cycles. Primary end‐points were the early and overall response rates. Results: One hundred and sixteen cycles of therapy were delivered. Hospital admissions were required following 27 treatment cycles (24%), predominantly following cycle 1. Febrile neutropenia followed 6% of cycles. The early and overall response rates on an intention‐to‐treat basis were 60 and 53%, respectively. Responses for peripheral T‐cell lymphoma and Hodgkin lymphoma were particularly encouraging, 70 and 75%, respectively. With a median follow up of 34 months overall survival for the entire cohort at 2 years is 50%. Furthermore, for the 23 patients who did not receive high‐dose consolidative therapy 2‐year survival was 35%. Conclusions: Vinorelbine and gemcitabine with filgrastim support can be safely delivered in an outpatient setting and shows clinically meaningful activity against a range of advanced lymphoma subtypes.     

Gemcitabine plus cisplatine and paclitaxel (GCP) in second-line treatment of germ cell tumors (GCT): a phase II study

The aim of the study was to determine the efficacy and toxicity of gemcitabine, cisplatin and paclitaxel (GCP) combination as a first salvage treatment of patients with relapsed GCT. Four courses of paclitaxel 175 mg/m(2) and cisplatin 50 mg/m(2), both on day 1, and gemcitabine 1000 mg/m(2), on days 1 and 8, every 3 weeks, were given to 12 consecutive patients who had failed standard 1st line treatment. Six patients (50%; 95% CI 21-79%) achieved favourable response and two of them are maintained 38+ and 29+ months. Median survival time was 16 months (range, 0.77-38+). All, but two patients had hematological toxicity Gr3-4 with infectious complication seen only in 6 courses of therapy. GCP is an active second-line combination regimen for relapsed GCTs with acceptable toxicity profile. However the results of this study did not show expected treatment efficacy and we raise the idea of cisplatin dosage relevance in this combination.     

Systemic gemcitabine combined with intra-arterial low-dose cisplatin and 5-fluorouracil for advanced hepatocellular carcinoma： Seven cases

The combination of intra-arterial low-dose cisplatin and 5-fluorouracil （5-FU） is effective against advanced hepatocellular carcinoma （HCC）. Systemic gemcitabine chemotherapy seems effective in many cancers. We report the results of combination therapy with systemic gemcitabine, intra-arterial low-dose cisplatin and 5-FU （GEMFP）. Seven patients with non-resectable advanced HCC were treated with GEMFP. One course of chemotherapy consisted of daily intra-arterial cisplatin （20 mg/body weight/hour on d 1, 10 mg/body weight per 0.5 h on d 2-5 and 8-12）, followed by 5-FU （250 mg/body weight per 5 h on d 1-5 and 8-12） via an injection port. Gemcitabine at 1000 mg/m2 was administered intravenously at 0.5 h on d 1 and 8. The objective response was 57%. The response to GEMFP was as follows： complete response （no patients）, partial response （four patients）, stable disease （three patients）, and progressive disease （no patients）. The median survival period was 8 mo （range, 5-55）. With regard to the National Cancer Institute Common Toxicity Criteria （NCI-CTC） grade 3 or 4 adverse reactions, seven （100%）, seven, six （86%） and one （14%） patients developed leukopenia, neutropenia, thrombocytopenia and anemia, respectively. GEMFP may potentially be effective for non- resectable advanced HCC, but it has severe hematologic toxicity.     

High response rate and manageable toxicity with an intensive, short-term chemotherapy programme for Burkitt's lymphoma in adults

A very short, intensive paediatric chemotherapy programme was tested in a consecutive monoinstitutional group of 22 adult Burkitt's lymphoma (BL) patients. After a 5-week induction phase of weekly infusions consisting of vincristine, cyclophosphamide, doxorubicin, high-dose (HD) methotrexate (MTX) plus leukovorin rescue, and intrathecal MTX or cytarabine (ARA-C), a consolidation phase including HD ARA-C plus cisplatin was given. Responding patients achieving less than complete response (CR) after completion of the initial induction phase, were promptly shifted to a high-dose, stem cell supported sequential chemotherapy schema (R-HDS). Patient characteristics: median age, 35.5 (range 18-76) years; Ann Arbor stage I-II/III-IV, 11/11; bulky disease, 15 patients; LDH > or = 460 U/l, 11 patients. The median duration of the chemotherapy programme was 62 d (range, 43-94 d). Seventeen patients achieved a CR (77%), one patient died of progressive disease and four partial responders following induction were converted to CR following R-HDS. Of 17 patients in CR, one died of infectious toxicity while in CR, and one relapsed at 30 months and died of progressive disease. After a median follow-up of 28.7 months (range, 6-158 months), 16 patients (73%) were in continued CR. Overall survival and progression-free survival were 77% [95% confidence interval (CI), 52-99%] and 68% (95% CI, 43-99%) respectively. Confirmation of these excellent efficacy and feasibility results by larger, multicentre and prospective studies is warranted.     

A phase I/II trial of bortezomib combined concurrently with gemcitabine for relapsed or refractory DLBCL and peripheral T‐cell lymphomas

There remains an unmet therapeutic need for patients with relapsed/refractory diffuse large B‐cell lymphoma (DLBCL) and peripheral T‐cell lymphoma (PTCL). We conducted a phase I/II trial with bortezomib (dose‐escalated to 1·6 mg/m²) given concurrently with gemcitabine (800 mg/m²) days 1 + 8 q21 d. Of 32 patients, 16 each had relapsed/refractory PTCL and DLBCL. Median prior therapies were 3 and 35% had failed transplant. Among the first 18 patients, 67% experienced grade 3/4 neutropenia and/or grade 3/4 thrombocytopenia resulting in repeated treatment delays (relative dose intensity: 46%). Thus, the study was amended to give bortezomib and gemcitabine days 1 + 15 q28 d, which resulted in markedly improved tolerability. Among all patients, the overall response rate (ORR) was 24% with 19% complete remission (CR; intent‐to‐treat (ITT) ORR 16%, CR 13%), which met criteria for futility. The ORR for DLBCL was 10% (CR 10%) vs. 36% for PTCL (CR 27%). Among 6 PTCL patients treated on the modified schedule, ORR by ITT was 50% (CR 30%). Altogether, concurrent bortezomib/gemcitabine given days 1 + 8 q21 d was not tolerable, while modification to a bi‐monthly schedule allowed consistent treatment delivery. Whereas efficacy of this combination was low in heavily pre‐treated DLBCL, there was a signal of activity in relapsed/refractory PTCL utilizing the modified schedule.     

Gemcitabine in locally advanced and/or metastatic bladder cancer

Gemcitabine is a promising new drug in patients with locally advanced and/or metastatic transitional cell carcinoma of the urothelium. The drug has been tested as a single-agent in one phase I study and four phase II studies. Gemcitabine was administered on days 1, 8 and 15 every 28 days with a dose in the phase II studies ranging from 1000 to 1250 mg/m(2). Response rates for single-agent gemcitabine in as well previously untreated as cisplatin-based pretreated patients ranged from 23 to 29% with CR rates between 4 and 13%. Toxicities were mild to modest and generally without grade 4 toxicities. The combination of gemcitabine and cisplatin has been tested in three phase II studies. Gemcitabine was administered in a dose of 1000 mg/m(2) on days 1, 8 and 15 every 28 days whereas the cisplatin dose and schedule varied. In one study, cisplatin was given in a dose of 35 mg/m(2) on days 1, 8, and 15 together with gemcitabine; in the two other studies in a dose of 70-75 mg/m(2) on day 1 or 2 in each treatment course. The response rates ranged from 42 to 66% with CR rates of 18, 21 and 28%. Median survival was reported in two of the studies, 12.5 and 13.2 months, respectively. Toxicities were generally manageable although the weekly schedule of cisplatin resulted in a high degree of grade 3-4 neutropenia and thrombocytopenia. Thus, the schedule has been optimized by use of monthly cisplatin in a dose of 70 to 75 mg/m(2). The two-drug combination of gemcitabine and cisplatin has also been compared with MVAC in a randomized phase III trial. Gemcitabine was administered in a dose of 1000 mg/m(2) on days 1, 8 and 15 and cisplatin in a dose of 70 mg/m(2) on day 2 every 28 days. The study was initiated late in 1996 and the planned recruitment of 400 patients was reached at the end of October 1998. The results are now eagerly awaited. Preliminary results for gemcitabine tested in two- and three-drug combinations with new agents such as paclitaxel have indicated response rates of up to 79% and these combinations should be further explored.     

Topotecan, Ara-C, cisplatin and prednisolone (TOPOSHAP) for patients with refractory and relapsing lymphomas: results of a phase I trial

We designed a phase I trial to assess the feasibility of the combination of topotecan, Ara-C, cisplatin and solumedrol (TOPOSHAP) in patients with relapsed or primary refractory lymphomas. We included 9 patients with measurable non-Hodgkin's (n = 8) and Hodgkin's (n = 1) lymphomas. Level 1 consisted of topotecan 1.0 mg/m(2)/day, i.v., given on days 1-3, cisplatin 25 mg/m(2)/day, i.v., on days 1-3, Ara-C 500 mg/m(2), i.v., on day 4, methylprednisolone 250 mg, i.v., on days 1-4. The regimen was repeated every 3-4 weeks. The maximum tolerated dose was already reached at level 1. G-CSF was added systematically after the 5th patient was included. The most significant toxicity in this trial was hematologic (all had neutropenia WHO grade 4 and 7 had grade 4 thrombocytopenia). Three patients had neutropenic fever. We observed two instances of WHO grade 3 and one of grade 4 diarrhea. Two patients achieved a complete response and 6 a partial response. We conclude that TOPOSHAP with G-CSF support is feasible and should be further studied in phase II studies.     

Combination chemotherapy with gemcitabine and vinorelbine in the treatment of relapsed or refractory diffuse large B-cell lymphoma: a phase-II trial by the Hellenic Cooperative Oncology Group

To investigate the efficacy and toxicity of the combination of gemcitabine and vinorelbine in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBL), 22 patients with relapsed or refractory DLBL were treated with gemcitabine 1000 mg/m2 and vinorelbine 30 mg/m2 on days 1 and 8 every 3 wk for a maximum of six cycles. Fourteen patients were considered chemosensitive while eight patients were considered chemoresistant to the last treatment regimen. All 22 patients were assessed for response to treatment. Three patients (14%) achieved complete remission and eight patients (36%) had partial remission of their disease, with an overall response rate of 50%. With a median follow up of 44 months, the median time to progression (TTP) for all patients was 8.1 months while the median overall survival (OS) was 12.9 months. Toxicity was minimal and all patients were treated on an outpatient basis. The combination of gemcitabine and vinorelbine is an effective and well-tolerated regimen for patients with relapsed of refractory DLBL.     

Phase I study of the combination of irinotecan hydrochloride,carboplatin, and dexamethasone for the treatment of relapsed or refractory malignant lymphoma

A phase I study of irinotecan hydrochloride (CPT-11), carboplatin, and dexamethasone treatment in 7 patients with relapsed lymphoma and 7 patients with refractory lymphoma was conducted to evaluate the maximal tolerated dose. The 6 female and 8 male patients had a median age of 63 years (range, 45-73 years), a median performance status of 0 (range, 0-2), and a median disease stage of IV. This study included patients with diffuse large B-cell lymphoma (n = 5), adult T-cell leukemia/lymphoma (n = 2), mantle cell lymphoma (n = 2), follicular lymphoma (n = 2), angioimmunoblastic T-cell lymphoma (n = 1), anaplastic large cell lymphoma (n = 1), and Hodgkin's lymphoma (n = 1). All patients had received anthracycline-containing combination chemotherapy prior to this therapy. The starting dosage of CPT-11 was 15 mg/m2 per day (days 1-3 and 8-10), and dosage-escalation increments of 5 mg/m2 per day were planned, with fixed dosages of carboplatin (250 mg/m2 per day, day 1) and dexamethasone (40 mg/body, days 1-3 and days 8-10). Five patients were enrolled at level 1, 3 at level 2, 4 at level 3, and 2 at level 4. Ten patients (71%) and 11 patients (79%) experienced grade 3 or 4 hematologic toxicities of leukocytopenia and neutropenia, respectively. Three patients (29%) and 9 patients (64%) experienced grade 3 or 4 thrombocytopenia and anemia, respectively. Two patients who received 30 mg/m2 (level 4) of CPT-11 developed sepsis. We concluded that the recommended dose of CPT-11 with carboplatin and dexamethasone is 25 mg/m2. No deaths were related to this chemotherapy, and no patient developed liver dysfunction. The overall response rate was 36%. We conclude that the combination therapy of CPT-11, carboplatin, and dexamthasone is effective as salvage therapy but that the duration of response is too short.     

High-dose cytosine arabinoside, total body irradiation and marrow transplantation for advanced malignant lymphoma

Twenty-four patients with advanced malignant lymphoma including Hodgkin's disease (HD, n = 1), intermediate grade non-Hodgkin's lymphoma (IGL, n = 12) and high-grade non-Hodgkin's lymphoma (HGL, n = 11) were prepared for syngeneic (n = 2), allogeneic (n = 11) or autologous (n = 11) marrow transplantation with cytosine arabinoside, 3 g/m2 every 12h for 12 doses (HDAC) and total body irradiation, 200 cGy daily for 6 days (TBI) to determine toxicity and efficacy. Eight patients (33%) died from early regimen related toxicity and all eight had a Karnofsky performance score less than or equal to 80 at the start of treatment. The actuarial probability of disease-free survival was 17% with a 65% probability of relapse at 4 years after transplantation. Four patients are surviving 2-4 years post-transplant, three transplanted for IGL and one for HD. None of the patients transplanted for HGL survived. The result of this phase II study suggests that HDAC followed by TBI and marrow infusion offers no apparent advantage over cyclophosphamide + TBI for patients with relapsed advanced malignant lymphoma. Earlier transplantation currently is the only demonstrated method of achieving better results.     

Predictive value of early 18F-fluoro-deoxyglucose positron emission tomography in chemosensitive relapsed lymphoma

18F-fluoro-deoxyglucose (FDG) positron emission tomography (PET) might be a better tool than computerized tomography (CT) in predicting long-term treatment outcome in patients with relapsed chemosensitive lymphoma who are candidates for autologous stem cell transplantation (ASCT). We studied patients with recurrent or persistent aggressive non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD), who were treated with three courses of second-line induction chemotherapy [DHAP-VIM (dexamethasone, cytarabine, cisplatin followed by etoposide, iphosphamide and methotrexate)-DHAP], followed by myeloablative therapy and ASCT if chemosensitive. FDG-PET was performed in parallel to conventional diagnostic methods before starting, and after two courses of, second-line therapy. Of 68 relapsed lymphoma patients, 46 chemosensitive patients (33 NHL and 13 HD) were included, of whom 39 were transplanted. After DHAP-VIM, the second PET scan was normalized in 15/46 patients; progression-free survival at 2 years was 62% for PET-negative patients versus 32% for PET-positive patients (P = 0.048). The relative risk for progressive disease in patients with < 90% intensity reduction was 2.85 (95% confidence interval 1.15-7.05, P = 0.018). Early FDG-PET may help to predict the long-term treatment outcome of ASCT in chemosensitive patients with relapsed lymphoma and identify those patients who need extra or alternative treatment. Disappearance or > 90% reduction of intensity of abnormal FDG uptake after two courses of reinduction therapy was correlated with a favourable outcome.     

Phase II study of gemcitabine and cisplatin in advanced biliary tract cancer

BACKGROUND: The aim of this phase II study was to determine the efficacy of gemcitabine plus cisplatin chemotherapy in patients with advanced biliary tract cancer. METHODS: Eligibility criteria included histologically confirmed adenocarcinoma with measurable tumor in the biliary tract that was unresectable and either locally advanced or metastatic. Patients received a combination of gemcitabine (1000 mg/m(2) intravenously [IV] on days 1, 8, and 15) and cisplatin (75 mg/m(2) IV on day 1). Cycles were repeated every 28 days. Objective tumor response rates and toxicities were evaluated according to World Health Organization criteria. RESULTS: Twenty-seven patients were enrolled in the study and a total of 120 cycles of chemotherapy were administrated. Objective partial response was observed in nine (33.3%) patients, while stable disease was found in seven (25.9%) patients. The median survival time was 10.0 months and the 1-year survival rate was 36%. Median time to disease progression was 5.6 months. The most common grade 3-4 toxicities were leukopenia (25.9%), anemia (29.6%), thrombocytopenia (22.2%), and vomiting (18.5%). Only one patient was hospitalized for chemotherapy-related complications. CONCLUSION: Gemcitabine and cisplatin combination chemotherapy is an effective, safe, and well-tolerated regimen for the treatment of advanced biliary tract cancer.     

Autologous tandem transplantation in patients with primary progressive or relapsed/refractory lymphoma

Patients with primary progressive or refractory Hodgkins disease (HD) or aggressive non-Hodgkins lymphoma (NHL) have a particularly poor prognosis. Here we report the results of autologous tandem transplantation in these patients. Patients aged 18–55 years with primary progressive or refractory relapsed HD and aggressive NHL were included. Patients received high-dose etoposide (2000 mg/m²) followed by peripheral blood stem cell harvest (PBSC). The first high-dose chemotherapy (TMC) consisted of thiotepa (750 mg/m²), mitoxantrone (40 mg/m²), and carboplatin (990 mg/m²). Patients with no change (NC), partial remission (PR), or complete remission (CR) after TMC then received BEAM with carmustine (300 mg/m²), etoposide (1200 mg/m²), cytarabine (1600 mg/m²), and melphalan (140 mg/m²). Patients with bulky disease (>5 cm) or residual lymphoma received involved field radiotherapy. Twenty-five patients were included (HD=10, NHL=15, median age 34 years). Two patients with HD achieved a CR and five patients a PR [response rate (RR) 70%]. Three patients (30%) experienced treatment failure including two deaths due to peritransplant complications. Five patients with aggressive NHL were in CR and two patients in PR (RR 46%). Of the eight patients (56%) with treatment failure, three had progressive disease and five died from peritransplant complications. Freedom from treatment failure (FFTF) and overall survival (OS) for all patients after 12 months was 28% and 40%, respectively. Tandem HDCT followed by autologous stem cell transplantation (ASCT) offers a chance of cure in these poor prognostic patients, but is associated with risks.J.-P. Glossmann and J. O. Staak have contributed equally to this work.     

Ifosphamide, etoposide and epirubicin is an effective combined salvage and peripheral blood stem cell mobilisation regimen for transplant-eligible patients with non-Hodgkin lymphoma and Hodgkin disease

A total of 143 patients with relapsed (n = 90), primary refractory (n = 32) and first line chemotherapy responsive (n = 21) non-Hodgkin lymphoma (NHL) and Hodgkin disease (HD) were treated with IVE (ifosphamide, etoposide and epirubicin) chemotherapy with the intent to proceed to high-dose therapy with either autologous or allogeneic transplantation, following peripheral blood stem cell mobilisation. A major response (complete/partial response) to IVE was seen in 115 patients (80.4%) with 5-year overall survival (OS) and event free survival (EFS) of 53% and 43%, respectively. Subgroup analysis showed overall response rates of 93.1% for HD with a 5-year OS and EFS of 62% and 52% respectively, while NHL showed response rates of 78.0% with 5-year OS and EFS of 50% and 39% respectively. The median number of CD34 +ve cells mobilised following IVE was 7.86 x 10(6) (range 1.72-42.91 x 10(6)), with 60% mobilising >2 x 10(6)/kg in a single collection. Grade IV neutropenia was seen in 79.6% patients and 77/270 cycles required intravenous antibiotic treatment. We conclude that IVE has a high response rate across a range of refractory and relapsed lymphoma with acceptable toxicity and excellent PBSC mobilising characteristics.